Airway medicine
By using a combination of live, purified Corynebacterium and Coccidia strains, the problem of insufficient intervention in the upper respiratory tract microbiome was solved, achieving protective and disease prevention and treatment effects on the nasal cavity and related systems.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- TRENCH THERAPEUTICS INC
- Filing Date
- 2021-05-27
- Publication Date
- 2026-04-17
AI Technical Summary
Current therapies do not adequately address the upper respiratory tract microbiome, leading to inflammation and pathogen colonization, which affects the health of the nasal cavity and related systems.
This invention provides a composition containing live, purified strains of Corynebacterium and Coccidia cuneiformis for modifying the upper respiratory tract microbiome, administered by spray, aerosol, or oral administration to reduce pathogen colonization and inflammation.
Effectively prevents and treats upper and lower respiratory tract diseases, including reducing pathogen colonization and inflammation, protecting the integrity of the nasal microbiome, and is applicable to the nasal cavity, lower respiratory tract, and central nervous system.
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Figure CN121868346A_ABST
Abstract
Description
[0001] This application is a divisional application of the application filed on May 27, 2021, with application number 202180048448.9 and invention title "Airway Drugs". Cross-reference to related applications
[0002] This application claims the benefit of U.S. Provisional Application No. 62 / 704,770, filed May 28, 2020, which is incorporated herein by reference in its entirety. Background Technology
[0003] Host and environmental factors can influence the integrity of a subject's gut microbiome. Microbial imbalance can lead to inflammation (and vice versa), resulting in opportunistic pathogen colonization and subsequent disease conditions. Probiotics offer therapeutic opportunities to address microbial imbalances and disease-related symptoms. Typically, probiotics in clinical development to date have focused on gut-colonizing bacteria. In some cases, interventions that promote improvement of the upper respiratory tract (especially the nasal cavity) microbiome environment may be needed to treat and prevent conditions in the nasal cavity and other systems connected to the upper respiratory tract via a shared mucosal network, such as the lower respiratory tract and the central nervous system. Additionally, the side effects of many current therapies (e.g., chemotherapy and radiation therapy) can increase inflammation and impair the airway microbiome. Summary of the Invention
[0004] This document provides compositions comprising pharmaceutical compositions, methods, kits, and devices for modifying the microbiome of a subject. As described in more detail herein, such compositions, among others, protect the integrity of the nasal microbiome and advantageously impart downstream effects on the upper respiratory tract (including the nasal cavity), lower respiratory tract (including the lungs), and central nervous system (including the olfactory system) for the prevention and / or treatment of disease symptoms. This document further provides mixtures of live, purified bacterial strains that provide multiple bactericidal mechanisms against pathogens, and in some cases, the live, purified bacteria are reciprocal in their relationship with each other. In some embodiments, the live, purified bacteria are selected from Corynebacterium (…). Corynebacterium species) and optionally, cunning cocci ( Dolosigranulum species). In some embodiments, the live, purified bacteria are Corynebacterium and / or Coccidia. In some embodiments, the live, purified bacteria include the strains listed in Table 1 and / or Table 2. In some embodiments, the Corynebacterium is Corynebacterium pseudodiphtheriae (… C. pseudodiphtheriticum ), crowded Corynebacterium ( C. accolens ), Corynebacterium amylopectin ( C. amycolatum), Corynebacterium propionate ( C. propinquum ), Corynebacterium glutamicum ( C. glutamicum ) or Corynebacterium bandingii ( C. striatum In some embodiments, the *Corynebacterium* is a combination of at least two species selected from the following: *Corynebacterium pseudodiphtheriae*, *Corynebacterium crowdingense*, *Corynebacterium amylopectinum*, *Corynebacterium propionate*, *Corynebacterium glutamicum*, and *Corynebacterium striatum*. In some embodiments, the *Corynebacterium* is *Corynebacterium pseudodiphtheriae*. In some embodiments, the composition comprises at least two strains of *Corynebacterium pseudodiphtheriae*. In some embodiments, the *Corynebacterium* is *Corynebacterium pseudodiphtheriae*, and *Coccus laziensis* is *Coccus laziensis*. This document further provides compositions wherein the live, purified bacteria comprise bacteria having a high percentage identity with the bacterial strains listed in Table 1 or Table 2, for example, at least 97% identity, based on comparison with the whole genome, the entire 16S rRNA region, or a hypervariable region of 16S rRNA (e.g., the V4 region). Attached Figure Description
[0005] Figure 1 In some embodiments, various dosage forms described herein for oral administration 101 and / or intranasal administration 102 are shown. The dosage forms shown include inhalers 103 for aerosol administration, liquids 104 and capsules 105 for oral administration, and spray bottles 106 for intranasal administration.
[0006] Figure 2A In some embodiments, a graph showing the OD600 measurement results of ATCC 10700 growth is displayed, where the Y-axis represents OD600 and the X-axis represents time in hours.
[0007] Figure 2B In some embodiments, a graph showing the OD600 measurement results of ATCC 10700 growth is displayed, where the Y-axis is Log(OD600) and the X-axis represents time in hours.
[0008] Figure 3A In some embodiments, a graph showing the OD600 measurement results of JCM 1320 growth is displayed, where the Y-axis represents OD600 and the X-axis represents time in hours.
[0009] Figure 3B In some embodiments, a graph showing the OD600 measurement results of JCM 1320 growth is displayed, where the Y-axis is Log(OD600) and the X-axis represents time in hours.
[0010] Figure 4AIn some embodiments, OD600 measurements of the growth of different numbers of ATCC 10700 and JCM 1320 cultures are shown, where the Y-axis represents OD600 and the X-axis represents time in hours.
[0011] Figure 4B In some embodiments, OD600 measurements of the growth of cultures with different numbers of ATCC 10700 and JCM 1320 are shown, where the Y-axis is Log(OD600) and the X-axis represents time in hours.
[0012] Figure 5 In some embodiments, the images are captured on an agar plate, showing four ATCC 10700 spots on the upper left and four JCM 1320 spots on the upper right. The images were captured 24 hours after growth.
[0013] Figure 6 In some embodiments, an image capture of an agar plate is shown, illustrating a column from left to right with two ATCC10700 spots, two *Leptococcus laziensis* spots, two *Leptococcus laziensis* spots, and two JCM 1320 spots. The image capture was taken 24 hours after growth. Detailed Implementation
[0014] This document provides compositions, methods, kits, and devices relating to upper respiratory tract colonizing bacteria for the prevention and / or treatment of respiratory and / or neurological symptoms. Furthermore, this document provides (1) probiotic bacterial mixtures; (2) excipients, dosage forms, and routes of administration for such mixtures; and (3) symptoms treated with such probiotic bacterial mixtures.
[0015] Throughout this disclosure, various embodiments are presented in range format. It should be understood that the range format description is merely for convenience and brevity and should not be construed as an inflexible limitation on the range of any embodiment. Therefore, unless the context clearly indicates otherwise, the description of a range should be considered as having specifically disclosed all possible subranges and individual values within the range up to one-tenth of the lower limit unit. For example, a description of a range such as 1 to 6 should be considered as having specifically disclosed subranges such as 1 to 3, 1 to 4, 1 to 5, 2 to 4, 2 to 6, 3 to 6, etc., and individual values within the range, such as 1.1, 2, 2.3, 5, and 5.9. The upper and lower limits of these intermediate ranges may be independently included in smaller ranges and are also covered within the invention, subject to any explicitly excluded limits in the stated ranges. Where a stated range includes one or both limits, it also includes ranges excluding any or both of those included limits, unless the context clearly indicates otherwise.
[0016] The terminology used herein is for the purpose of describing particular instances only and is not intended to limit any embodiments. As used herein, unless the context clearly indicates otherwise, the singular forms “a / an” and “the” are intended to also include the plural forms. As used herein, the term “and / or” includes any and all combinations of one or more of the associated listed items.
[0017] Unless specifically stated or clearly apparent from the context, as used herein, the term “about” when referring to a number or range of numbers is understood to mean the number stated and numbers plus or minus 10%, or values listed for a range that are 10% below the lower limit and 10% above the upper limit.
[0018] As used in this article, the term "subject" includes both human and non-human mammals, including, for example, primates, cattle, horses, pigs, sheep, goats, dogs, cats, or rodents, which are capable of being colonized by other organisms.
[0019] In some embodiments, this document provides compositions comprising bacteria having an identity percentage based on a 16S rRNA bacterial genetic sequence, a hypervariable region of 16S rRNA, or a comparison with the whole genome of a reference strain. Typically, comparison of 16S rRNA bacterial genetic sequences allows identification of a strain belonging to the same species as another strain by comparing the sequence with known bacterial DNA sequences using an NCBI BLAST search. The level of identity associated with the nucleotide sequence can be determined for at least 20, 30, 40, 50, 60, or 100 consecutive nucleotides. In some embodiments, the level of identity associated with the nucleotide sequence is determined for the entire sequence being searched. The percentage of identity with a reference bacterial 16S rRNA sequence, 16S rRNA V4 region sequence, or whole genome sequence can be at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%. The percentage of identity with the following reference bacterial 16S rRNA sequences may be at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% for the V1, V2, V3, V5, V6, V7, V8, or V9 regions.
[0020] In some embodiments, live bacteria may include bacteria that maintain membrane stability. In some embodiments, live bacteria may include bacteria capable of transcription and translation. In some embodiments, live bacteria may include bacteria capable of cell division. In some embodiments, live bacteria may be identified using culture-dependent or culture-independent techniques. In some cases, live bacteria may include a single bacterium or a group of bacteria that can produce colony-forming units (CFUs) when plated on a stable growth medium. In some embodiments, live and / or dead bacteria may be identified by imaging, for example using live / dead staining agents. In some embodiments, viability-based PCR methods may be used to identify live bacteria. In some cases, metabolomics assays may be used to identify live bacteria.
[0021] In some embodiments, references to a bacterial community or a purified community refer to a variety of bacteria.
[0022] 1) Probiotic mixture The nasal cavity of the upper respiratory tract is a nutrient-poor, high-salinity niche where bacteria compete for limited resources. A healthy nasal microbiome prevents the colonization of pathogenic microorganisms, the harmful byproducts of such colonization, inflammation, and the formation of "leaky" cell-cell junctions—all of which can lead to subsequent disease symptoms in other organs, including the lungs and central nervous system (CNS), along a shared mucosal network. Regarding the CNS, many neurological disorders are associated with olfactory dysfunction, such as anosmia. The olfactory nerve (cranial nerve I) is the shortest cranial nerve, where the cell bodies of primary olfactory neurons reside in the neuroepithelium, and their dendrites extend into the nasal cavity. Damage to olfactory epithelial cells, such as damage induced by pathogens or chemicals, can lead to the removal of the protective mucosal barrier and the death of olfactory neurons, resulting in an open channel from the olfactory epithelial cells to the bulbar cavity, creating pathways for pathogens or their material to bypass the blood-brain barrier. Therefore, the nasal cavity offers an opportunity to confer beneficial microbial changes to prevent and / or treat many disease symptoms. For example, in small human trials, a beneficial strain of *Corynebacterium pseudodiphtheriae* (*Corynebacterium pseudodiphtheriae* strain "090104) was reported to eliminate *Staphylococcus aureus* in the nasal cavities of volunteers exposed to anomalous microclimates and altered gaseous environments. Staphylococcus aureus From the nasal cavity in volunteers exposed to abnormal microclimate and altered gaseous environment, Kiryukhina et al., "Probiotics and Antimicrobial Proteins" Probiotics and Antimicrobial Proteins ) The efficacy of the strain in (2013) was demonstrated. Nasal spray application of the strain eradicated Staphylococcus aureus in three subjects and reduced its activity against methicillin-resistant Staphylococcus aureus (MRSA). methicillin-resistant S. aureus, The presence of MRSA carriers.
[0023] The bacteria described herein are intended for the control, treatment, reduction, elimination, and / or prevention of pathogenic colonization and / or inflammation in a subject. The compositions described herein can be administered or engineered for delivery to specific locations in a subject, particularly the upper respiratory tract including the anterior nasal cavity, nasal cavity, and / or nasopharynx. The bacterial strains described herein can be isolated from upper respiratory tract regions, including, but not limited to, the anterior nasal cavity, nasal cavity, and / or nasopharynx.
[0024] In some embodiments, compositions having a bacterial community having one or more species and one or more strains for each of the one or more species are provided herein. In some cases, the compositions described herein contain 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more bacterial species. In some cases, the compositions described herein contain 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more bacterial strains. Further, compositions comprising at least one Corynebacterium are provided herein. Further, compositions comprising multiple Corynebacteria are provided herein. Corynebacteria are Gram-positive bacteria that do not form spores and are non-motile. Exemplary Corynebacteria included in the compositions described herein include: crowded Corynebacterium, non-fermenting Corynebacterium (… C. afermentans ) 、 ammonia-producing Corynebacterium ( C. ammoniagenes ) 、 Corynebacterium amylopectin ,silver Corynebacterium chromatophores ( C. argentoratense ) 、 Aquatic Corynebacterium ( C. aquaticum ) 、 Corynebacterium auriculi ( C. auris ) 、 Corynebacterium bovis ( C. bovis ) 、 Corynebacterium diphtheriae (C. diphtheria Corynebacterium equinae ( C. equi (The current Rhodococcus equi ( Rhodococcus equi )), effective corynebacteria ( C. efficiens ), Corynebacterium fulvidracosum ( C. flavescens ), Glucoside-degrading Corynebacterium ( C. glucuronolyticum Corynebacterium glutamicum 、 Corynebacterium granulomatum ( C. granulosum ), hemolytic corynebacterium ( C. haemolyticum), Haloxylon ammodendron ( C. halofytica Corynebacterium koraiensis ( C. kroppenstedtii Corynebacterium jejuni ( C. jeikeium ), Corynebacterium micranthae ( C. macginleyi Corynebacterium martensii ( C. matruchotii ), fine corynebacteria ( C. minutissimum ), short rod-shaped bacteria ( C. parvum (Propionibacterium acnes () Propionibacterium acnes ), and micro-metabolizing Corynebacterium ( C. paurometabolum ), Corynebacterium propionate, Corynebacterium pseudodiphtheriae (Corynebacterium hoffmannii ( C. hofmannii Corynebacterium pseudotuberculosis ()), C. pseudotuberculosis Corynebacterium sheepii ( C. ovis ), Corynebacterium pyogenes ( C. pyogenes ) — Cryptococcus pyogenes ( Trueperella pyogenes ), Ureaplasma urealyticum ( C. urealyticum ), Corynebacterium nephritis ( C. renale Corynebacterium, Corynebacterium bandingense 、 Corynebacterium microphyllum ( C. tenuis ), Corynebacterium ulcerans ( C. ulcerans ), Corynebacterium urealyticum and Corynebacterium xylogenes ( C. xerosis In some cases, the compositions described herein include strains 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10 of the *Corynebacterium* strains listed in Table 1. In some embodiments, the bacterial population described herein includes *Corynebacterium* strains whose 16S rRNA sequences have at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity with the sequences of the strains listed in Table 1. In some embodiments, the bacterial population described herein includes *Corynebacterium* strains whose 16S rRNA sequences have at least 97% sequence identity with the sequences of the strains listed in Table 1. Sequence identity may be based on 16S rRNA sequences, 16S rRNA hypervariable region sequences such as V4, or whole-genome comparison. The bacterial population may be part of a pharmaceutical composition. The bacteria may be live and purified.
[0025] Table 1. Corynebacterium strains
[0026] In some embodiments, this document provides a bacterial population comprising at least one *C. laziensis*. This document further provides bacterial populations comprising multiple *C. laziensis* species. In some embodiments, this document provides a bacterial population comprising at least one *C. laziensis* strain. In some cases, the compositions described herein comprise strains 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10 of the *C. laziensis* strains listed in Table 2. In some embodiments, the bacterial population described herein comprises *C. laziensis* strains whose 16S rRNA sequences have at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity with the sequences of the strains listed in Table 2. In some embodiments, the bacterial population described herein comprises *C. laziensis* strains whose 16S rRNA sequences have at least 97% sequence identity with the sequences of the strains listed in Table 2. Sequence identity may be based on 16S rRNA sequences, 16S rRNA hypervariable region sequences such as V4, or whole-genome comparison. The bacterial population may be part of a pharmaceutical composition. Bacteria can be live or purified.
[0027] Table 2. Strains of *Coccidia cuneiformis*
[0028] This document further provides bacterial populations for colonization of the upper respiratory tract, comprising combinations of strains from different species. In some embodiments, the bacterial population includes at least one strain of the genus *Corynebacterium* and at least one strain of *Corynebacterium cuneiformis*. In some embodiments, the bacterial population includes at least one strain of *Corynebacterium pseudodiphtheriae* and at least one strain of *Corynebacterium laziness*. In some embodiments, the bacterial population includes at least one strain listed in Table 1 and at least one strain listed in Table 2. In some embodiments, the bacterial population includes at least one strain whose 16S rRNA sequence has at least 97% sequence identity with the sequences of the strains listed in Table 1; and at least one strain whose 16S rRNA sequence has at least 97% sequence identity with the sequences of the strains listed in Table 2. In other embodiments, one, two, three, or more of the *Corynebacterium* strains are *Corynebacterium pseudodiphtheriae* strains. The bacterial population may be part of a pharmaceutical composition. The bacteria may be live and purified. The compositions described herein may have a mixture of multiple species. The mixture may contain up to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more species, and may include species listed in Tables 1 and / or 2. Such species may be present in equal or different amounts. In some embodiments, each different species is present at least 1%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, or 100% of colony-forming units (CFU) for the total CFU of the bacterial population. The compositions described herein may be mixtures of strains within a single species. The mixture may contain up to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more strains, and may be from species listed in Tables 1 and / or 2. Such strains may be present in equal or different amounts. In some embodiments, different strains are present at at least 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, or 100% of colony-forming units (CFU) for the total CFU of the bacterial population.
[0029] In some embodiments, when administered to a subject, the bacterial populations described herein reduce or eliminate the colonization of pathogens in the respiratory tract. Exemplary respiratory pathogens include, but are not limited to, Staphylococcus aureus, Streptococcus pneumoniae, Pseudomonas aeruginosa, and Burkholderia pseudomallei. Table 3 lists exemplary strains of such pathogens. The reduction of such pathogens may occur in the upper or lower respiratory tract.
[0030] Table 3. Pathogens
[0031] 2) Excipients, dosage form and route of administration For ease of administration, the pharmaceutical compositions described herein may comprise one or more pharmaceutically acceptable excipients. Examples of pharmaceutically acceptable excipients include, but are not limited to, diluents, adjuvants, excipients, water, and oils (including petroleum, animal, vegetable, or synthetic oils). Other examples include saline, gum arabic, gelatin, starch paste, talc, keratin, colloidal silica, and urea. Such excipients may comprise binders such as ethyl cellulose, carboxymethyl cellulose, microcrystalline cellulose, or gelatin; excipients such as starch, lactose, or dextrin; disintegrants such as alginate, sodium alginate, Primogel, and corn starch; lubricants such as magnesium stearate or Sterotex; flow aids such as colloidal silica; sweeteners such as sucrose or saccharin; and flavoring or coloring agents such as peppermint, methyl salicylate, or orange flavoring. Further examples of excipients include polyethylene glycol, cyclodextrin, oils, or any other similar liquid carriers that can be formulated into capsules. Other examples of excipients include sterile diluents such as water, saline solution, physiological saline, Ringer's solution, and isotonic sodium chloride; fixed oils such as synthetic monoglycerides or diglycerides, polyethylene glycol, glycerol, cyclodextrin, propylene glycol, or other solvents; antimicrobial agents such as benzyl alcohol or methylparaben; antioxidants such as ascorbic acid or sodium bisulfite; chelating agents such as ethylenediaminetetraacetic acid; buffers such as acetates, citrates, or phosphates; and agents for tension regulation such as sodium chloride or dextran, thickeners, lubricants, and colorants. In some embodiments of the invention, a pharmaceutically acceptable carrier may include a growth medium that can support the growth and / or static presence of the beneficial bacteria described herein in the context of the pharmaceutical composition prior to administration of the pharmaceutical composition to a subject.
[0032] In some cases, the pharmaceutical compositions described herein contain materials in a physical form capable of altering dosage units. For example, the various dosage forms described herein... Figure 1The instructions specify oral administration 101 and / or intranasal administration 102. The dosage forms of the compositions described herein include nebulizers or inhalers 103 for aerosol administration, liquids 104 and capsules 105 for oral administration, and spray bottles 106 for intranasal administration. In some cases, the pharmaceutical compositions described herein are contained within nasal spray bottles. In some cases, the pharmaceutical compositions described herein are prepared as aerosols. Aerosols encompass a variety of systems including gels and pressurized packaging. Delivery of this form of composition may involve propelling the pharmaceutical composition containing the beneficial bacteria described herein using liquefied gas or other compressed gas or via a suitable pump system. Aerosols can be delivered in single-phase, two-phase, or three-phase systems. The compositions containing the pharmaceutical compositions described herein can be formulated according to the route of administration. Such forms include, but are not limited to, solutions, suspensions, emulsions, creams, gels, lotions, ointments, tablets, sheets, films, pills, granules, capsules, capsules containing liquids, powders, sustained-release formulations, directed-release formulations, lyophilized products (freeze-dried / lyophilized), aerosols, sprays, granules, or syrups. Dosage forms may be, but are not limited to, liquids, solids, semi-solids, gels, or aerosols. Methods of administration include, but are not limited to, oral, intranasal, or inhalation. The pharmaceutical compositions described herein may comprise a kit in which the bacteria described herein are contained in a first container (e.g., frozen stem cells), and one or more pharmaceutically acceptable excipients are contained in a second container (e.g., water). In some embodiments, a kit is provided herein comprising: a first container comprising a live, purified, and lyophilized bacterial population, the live, purified, and lyophilized bacterial population including: multiple strains of Corynebacterium pseudodiphtheriae; and a second container comprising a pharmaceutically acceptable excipient. In some embodiments, this document provides a kit comprising: a first container comprising a live, purified, and lyophilized bacterial population, the live, purified, and lyophilized bacterial population including multiple Corynebacterium species; and a second container comprising a pharmaceutically acceptable excipient. In some embodiments, this document provides a kit comprising: a first container comprising a live, purified, and lyophilized bacterial population, the live, purified, and lyophilized bacterial population including multiple *Corynebacterium pseudodiphtheriae* strains; and a second container comprising a pharmaceutically acceptable excipient. In some embodiments, this document provides a kit comprising: a first container comprising a live, purified, and lyophilized bacterial population, the live, purified, and lyophilized bacterial population including multiple *Corynebacterium pseudodiphtheriae* strains; and multiple *Corynebacterium laziness* strains; and a second container comprising a pharmaceutically acceptable excipient.In some embodiments, this document provides a kit comprising: a first container comprising a live, purified, and lyophilized bacterial population present in a total amount of at least 10^3 CFU, the live, purified, and lyophilized bacterial population comprising: *Corynebacterium pseudodiphtheriae* strains; and *Coccidia laziensis* strains; and a second container comprising pharmaceutically acceptable excipients. This document further provides a kit wherein the live, purified, and lyophilized bacterial population is present in a total amount of up to 10^15 CFU. This document further provides a kit wherein the live, purified, and lyophilized bacterial population is present in a total amount of 10^3 to 10^12 CFU.
[0033] Dosing may comprise a single or multiple administration of the pharmaceutical composition described herein. Examples include: multiple times a day, once daily, every other day, 1, 2, 3, 5, 6, or 7 times a week, once a week or less, a single administration, a course of treatment involving several treatments, either periodically or irregularly, or multiple administrations over a period of time until colonization reduction is achieved. In some cases, dosing may be administered daily, for 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 1 year, 2 years, or as needed. Dosing regimens that include the regularity and manner of administration may depend on factors including, but not limited to, the subject receiving treatment; the severity of the condition; the manner of administration; the stage of colonization; the presence of one or more other conditions, such as pregnancy, infancy, or the presence of one or more additional diseases. In some embodiments, the subject is an infant. The infant may be up to 24 months old. In some embodiments, the subject is a child. The child may be 2 to 21 years old. In some embodiments, the subject is an adult. An adult may be 21 years of age or older. In some embodiments, an adult is of advanced age, such as 65 years of age or older.
[0034] The compositions comprising a pharmaceutical composition described herein may include a single (unit) dose of bacteria. The compositions described herein may include about 10 2 To about 10 15 The compositions described herein may comprise about 10 colony-forming units (cfu) of bacteria or bacterial strains as described herein. 2 cfu to 10 12 cfu, 10 3 cfu to 10 12 cfu, 10 3 cfu to 10 11 cfu, 10 3 cfu to 10 10 cfu, 103 cfu to 10 9 cfu, 10 3 cfu to 10 8 cfu, 10 3 cfu to 10 7 cfu, 10 3 cfu to 10 6 cfu, 10 3 CFU to approximately 10 5 cfu, 10 3 cfu to 10 4 cfu, 10 4 cfu to 10 12 cfu, 10 4 cfu to 10 11 cfu, 10 4 cfu to 10 10 cfu, 10 4 cfu to 10 9 cfu, 10 4 cfu to 10 8 cfu, 10 4 cfu to 10 7 cfu, 10 4 cfu to 10 6 cfu, 10 5 cfu to 10 12 cfu, 10 5 cfu to 10 11 cfu, about 10 5 CFU to approximately 10 10 cfu, 10 6 cfu to 10 12 cfu, 10 7 cfu to 10 12 cfu, 10 8 cfu to 10 12 cfu, 10 9 cfu to 10 12 cfu, 10 10 cfu to 10 12 cfu, 10 11 cfu to 10 12 CFU or 10 6 cfu to 10 10 The bacteria or bacterial strains described herein are CFU. In some embodiments, the composition comprises about 10 3 cfu, about 10 4 cfu, about 10 5cfu, about 10 6 cfu, about 10 7 cfu, about 10 8 cfu, about 10 9 cfu, about 10 10 cfu, about 10 11 CFU or approximately 10 12 The bacteria or bacterial strains described in this article are cfu.
[0035] The composition comprising a pharmaceutical composition described herein may include 10 per mL. 2 Up to 10 15 Each colony-forming unit (CFU) of the bacteria or bacterial strains described herein may comprise approximately 10 CFU per mL of the compositions described herein. 2 cfu to 10 12 cfu, 10 3 cfu to 10 12 cfu, 10 3 cfu to 10 11 cfu, 10 3 cfu to 10 10 cfu, 10 3 cfu to 10 9 cfu, 10 3 cfu to 10 8 cfu, 10 3 cfu to 10 7 cfu, 10 3 cfu to 10 6 cfu, 10 3 CFU to approximately 10 5 cfu, 10 3 cfu to 10 4 cfu, 10 4 cfu to 10 12 cfu, 10 4 cfu to 10 11 cfu, 10 4 cfu to 10 10 cfu, 10 4 cfu to 10 9 cfu, 10 4 cfu to 10 8 cfu, 10 4 cfu to 10 7 cfu, 10 4 cfu to 10 6 cfu, 10 5 cfu to 1012 cfu, 10 5 cfu to 10 11 cfu, about 10 5 CFU to approximately 10 10 cfu, 10 6 cfu to 10 12 cfu, 10 7 cfu to 10 12 cfu, 10 8 cfu to 10 12 cfu, 10 9 cfu to 10 12 cfu, 10 10 cfu to 10 12 cfu, 10 11 cfu to 10 12 CFU or 10 6 cfu to 10 10 The bacteria or bacterial strains described in this article are cfu.
[0036] The compositions described herein may include at least about 0.01% by weight, at least about 0.05% by weight, at least about 0.1% by weight, at least about 0.2% by weight, at least about 0.3% by weight, at least about 0.4% by weight, at least about 0.5% by weight, at least about 0.6% by weight, at least about 0.7% by weight, at least about 0.8% by weight, at least about 0.9% by weight, at least about 1.0% by weight, at least about 1.5% by weight, at least about 2.0% by weight, at least about 3.0% by weight, at least about 4.0% by weight, at least about 5.0% by weight, at least about 6.0% by weight, at least about 7.0% by weight, and at least about 8.0% by weight. %, at least about 9.0% by weight, at least about 10.0% by weight, at least about 11.0% by weight, at least about 12.0% by weight, at least about 13.0% by weight, at least about 14.0% by weight, at least about 15.0% by weight, at least about 16.0% by weight, at least about 17.0% by weight, at least about 18.0% by weight, at least about 19.0% by weight, at least about 20.0% by weight, at least about 25.0% by weight, at least about 30.0% by weight, at least about 35.0% by weight, at least about 40.0% by weight, at least about 45.0% by weight, or at least about 50.0% by weight of the bacteria or bacterial strains described herein.
[0037] The compositions comprising pharmaceutical compositions described herein may include the following ratios (CFU to CFU): approximately 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:20, 1:30, 1:40, 1:50, 1:60, 1:70, 1:80, 1:90, 1:100, 1:200, 1:300, 1:400, 1:500, 1:600, 1:700, 1:800, 1:900, or approximately 1:1000 of the strains in Table 1 and another strain in Table 1 or the strains in Table 2 and another strain in Table 2. The compositions comprising pharmaceutical compositions described herein may include the following ratios (CFU to CFU): approximately 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:20, 1:30, 1:40, 1:50, 1:60, 1:70, 1:80, 1:90, 1:100, 1:200, 1:300, 1:400, 1:500, 1:600, 1:700, 1:800, 1:900, or approximately 1:1000 of the strains in Table 1 and the strains in Table 2. The compositions comprising pharmaceutical compositions described herein may include a variety of Corynebacterium and / or Lazycoccus strains in ratios (CFU to CFU) of approximately 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:20, 1:30, 1:40, 1:50, 1:60, 1:70, 1:80, 1:90, 1:100, 1:200, 1:300, 1:400, 1:500, 1:600, 1:700, 1:800, 1:900, or approximately 1:1000.
[0038] 3) Symptoms In some embodiments, this document provides compositions for the prevention or treatment of respiratory symptoms. Such symptoms, as described in more detail herein, pertain to the upper and / or lower respiratory tract. The upper airway or upper respiratory tract typically includes the nose and nasal passages, sinuses, pharynx, and the portion of the larynx above the vocal folds (bands). The lower airway or lower respiratory tract typically includes the larynx below the vocal folds, the trachea, and the bronchi, bronchioles, and alveoli that constitute the lungs. These structures inhale air from the upper respiratory system, absorb oxygen, and release carbon dioxide as an exchange. In some embodiments, the described compositions include beneficial bacteria present in an amount sufficient to reduce the incidence of pathogen colonization. In some embodiments, the symptoms are related to a bacterial infection. Sources of bacterial infection prevented or treated by the pharmaceutical compositions described herein include, but are not limited to, Staphylococcus aureus (methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive Staphylococcus aureus (MSSA)), Streptococcus pneumoniae, Pseudomonas aeruginosa, and Bordetella pertussis (…). Bordetella pertussisUpper respiratory tract symptoms treated or prevented by administration of the compositions described herein include, but are not limited to, allergic rhinitis or non-allergic rhinitis, including acute bacterial sinusitis. Lower respiratory tract symptoms treated or prevented by administration of the compositions described herein include, but are not limited to, asthma, tuberculosis, pertussis (epidemic cough), pneumonia (including hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), and community-acquired pneumonia (CAP)), walking pneumonia, as well as bronchitis, lung cancer, cystic fibrosis, chronic obstructive pulmonary disease (COPD) (e.g., emphysema or chronic bronchitis), idiopathic pulmonary fibrosis (IPF), and interstitial lung disease (ILD). In some embodiments, the pharmaceutical compositions described herein are optionally administered to Staphylococcus aureus-positive subjects prior to ventilator therapy. In other embodiments, the subject is diagnosed with COVID. In some embodiments, the pharmaceutical compositions described herein are optionally administered to coronavirus (CoV)-positive subjects (e.g., SARS-CoV-2, SARS-CoV Tor2, and MERS-CoV) prior to ventilator therapy. In some embodiments, asthma is childhood asthma, adult episodic asthma, occupational asthma, severe asthma, or seasonal asthma. In some embodiments, lung cancer is small cell lung cancer or non-small cell lung cancer (NSCLC), including adenocarcinoma, squamous cell carcinoma, or large cell carcinoma. Exemplary lung cancers include, but are not limited to, primary pulmonary lymphoma, lymphangiocarcinoma, epithelioid angioendothelioma or multicystic lung disease (MCLD), sarcomatoid carcinoma, adenosquamous carcinoma, salivary gland type lung cancer, large cell neuroendocrine carcinoma, granular cell lung cancer, carcinoid, or atypical carcinoid. In some embodiments, cancer is lip cancer, tongue cancer, mouth cancer, oral cavity cancer, oropharyngeal cancer. Exemplary cancers in this region include, but are not limited to, laryngeal cancer, nasopharyngeal carcinoma, oral squamous cell carcinoma, oropharyngeal squamous cell carcinoma, ear tumors, salivary gland tumors, and sinus cancer. In some embodiments, the pharmaceutical compositions provided herein are adjuvants for treating the respiratory symptoms described herein. In some embodiments, the cancer is stage I, II, III, or IV. In some embodiments, the cancer is metastatic. In some embodiments, the pharmaceutical compositions described herein are adjuvants for chemotherapy used to treat cancer. In some embodiments, the cancer is a solid tumor or a hematopoietic system cancer. Exemplary solid tumors include, but are not limited to, carcinoma and sarcoma. Exemplary hematopoietic system cancers include, but are not limited to, leukemia, myeloma, and lymphoma (including Hodgkin lymphoma or non-Hodgkin lymphoma, NHL).Example chemotherapeutic agents include, but are not limited to, etoposide optionally combined with platinum (cisplatin or carboplatin), 5-fluorouracil (5-FU), paclitaxel, docetaxel, hydroxyurea, methotrexate, bleomycin, and capecitabine. In some embodiments, at least one chemotherapeutic agent is used. In some embodiments, radiation (ionizing radiation) is administered. In some embodiments, radiation (ionizing radiation) and chemotherapy are administered. Therapies such as chemotherapy and radiation may induce an inflammatory response and disrupt the integrity of cell-cell junctions, leading to additional disease symptoms such as oral mucositis. In some embodiments, the pharmaceutical compositions described herein are administered as adjuvants with one or more checkpoint inhibitors to treat cancer. Exemplary checkpoint inhibitors include, but are not limited to, anti-CTLA-4 antibodies (e.g., ipilimumab), anti-PD-L1 antibodies (e.g., atezolizumab), and anti-PD-1 antibodies (e.g., nivolumab and pembrolizumab). In some embodiments, the pharmaceutical compositions described herein are administered as a treatment for viral symptoms or as adjuvants to a therapy for viral symptoms. In other embodiments, the virus is a respiratory virus. Exemplary respiratory viruses include, but are not limited to, influenza A (e.g., H1N1 and H1N5), influenza B, adenovirus, respiratory syncytial virus (RSV), enterovirus (EV), human rhinovirus (HRV), human metapneumovirus (HMPV), human bocavirus (HBoV), coronaviruses (CoV) (e.g., SARS-CoV-2, SARS-CoV Tor2, and MERS-CoV), and parainfluenza virus (PIV). Exemplary treatments for viral symptoms include, but are not limited to, oseltamivir, zanamivir, ribavirin, palivizumab, and aspirin. In some embodiments, the pharmaceutical compositions described herein are optionally administered to SARS-CoV-2 positive subjects prior to receiving mechanical ventilation. In some embodiments, pharmaceutical compositions for treating or preventing the respiratory symptoms described herein comprise at least one species (or strain) listed in Table 1 or Table 2, or a mixture listed in Tables 4 through 7. In some embodiments, the pharmaceutical compositions described herein are optionally administered to subjects suffering from respiratory symptoms prior to receiving mechanical ventilation. In some embodiments, pharmaceutical compositions for treating or preventing the respiratory symptoms described herein include strains of Corynebacterium pseudodiphtheriae and optionally strains of Coccidia laziensis.In some embodiments, a method is provided for treating nasal colonization of at least one pathogenic microorganism in a subject, the method comprising the step of administering a pharmaceutical composition to the subject, wherein the pharmaceutical composition comprises Corynebacterium strains listed in Table 1 and Coccidia strains listed in Table 2. In some embodiments, a method is provided for treating nasal colonization of at least one pathogenic microorganism in a subject, the method comprising the step of administering a pharmaceutical composition to the subject, wherein the pharmaceutical composition comprises Corynebacterium pseudodiphtheriae strains listed in Table 1 and Coccidia strains listed in Table 2 or a mixture listed in Tables 4 to 7. In some embodiments, a method is provided herein for reducing the colonization of pathogenic microorganisms in the anterior nasal cavity or nasal cavity of a subject, the method comprising the step of administering a live, purified bacterial population to the subject who has pathogenic microorganisms in the anterior nasal cavity or nasal cavity of the subject, wherein the live, purified bacterial population comprises multiple Corynebacterium pseudodiphtheriae strains. A method is further provided herein in which the pathogenic microorganism comprises Staphylococcus aureus, Streptococcus pneumoniae, or Pseudomonas aeruginosa. A method is further provided herein in which the live, purified bacterial population comprises a mixture listed in Tables 4 to 7. This document further provides a method wherein the live, purified bacterial population comprises a mixture listed in Tables 4 to 7. This document further provides a method wherein the multiple *Corynebacterium pseudodiphtheriae* strains include JCM 1320 or ATCC 10700. This document further provides a method wherein the multiple *Corynebacterium pseudodiphtheriae* strains include JCM 1320 and ATCC 10700. This document further provides a method wherein the multiple *Corynebacterium pseudodiphtheriae* strains include strains selected from those listed in Table 1. This document further provides a method for reducing the colonization of pathogenic microorganisms in the anterior nasal cavity or nasal cavity of a subject, the method comprising the step of: administering a live, purified bacterial population to the subject who has pathogenic microorganisms in the anterior nasal cavity or nasal cavity of the subject, wherein the live, purified bacterial population comprises multiple *Corynebacterium* species. This document further provides a method wherein the multiple *Corynebacterium* species include *Corynebacterium bulgaricum*, *Corynebacterium pseudodiphtheriae*, *Corynebacterium amylopectinum*, *Corynebacterium propionate*, *Corynebacterium glutamicum*, or *Corynebacterium bandingense*. This document further provides methods in which the pathogenic microorganisms include Staphylococcus aureus, Streptococcus pneumoniae, or Pseudomonas aeruginosa. In some embodiments, this document provides a method for restoring olfactory loss, the method comprising: administering to a subject suffering from airway inflammatory symptoms a live, purified bacterial population, wherein the live, purified bacterial population includes a variety of Corynebacterium species.
[0039] In some embodiments, this document provides compositions for the prevention or treatment of neurological symptoms. In some embodiments, the neurological symptoms are symptoms associated with olfactory perception deficits. In some embodiments, a subject with a neurological symptom is identified as having an olfactory perception deficit, for example, by a marker of reduced olfactory ability. Olfactory hyposmia or anosmia is a symptom associated with the onset of various neurological disorders involving impaired cellular and mucosal barrier integrity that protects the CNS, particularly in the microenvironment near the olfactory nerves. In some embodiments, the neurological condition is Parkinson's disease (PD), incidental Lewy body disorder (iLBD), dementia with Lewy bodies (DLB), Alzheimer's disease (AD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP), frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), pure autonomic failure (PAF), schizophrenia, Creutzfeldt-Jakob disease (CJD), autism spectrum disorder (ASD), post-traumatic stress disorder (PTSD), anxiety disorder, or depression. In some embodiments, ASD is autism, pervasive developmental disorder (PDD-NOS), Asperger's syndrome, childhood disintegration disorder (CDD), or Rett syndrome. In some embodiments, the anxiety disorder is generalized anxiety disorder, obsessive-compulsive disorder, panic disorder, post-traumatic stress disorder, or social phobia. In some embodiments, the described composition includes beneficial bacteria present in an amount sufficient to reduce the incidence of pathogen colonization. In some embodiments, the symptom is related to a bacterial infection. Sources of bacterial infections prevented or treated with the pharmaceutical compositions described herein include, but are not limited to, Staphylococcus aureus (methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive Staphylococcus aureus (MSSA)), Streptococcus pneumoniae, Pseudomonas aeruginosa, Bordetella pertussis, and Burkholderia pseudomallei (associated with melioidosis). In some embodiments, the pharmaceutical compositions described herein are administered as a treatment for viral symptoms or as adjuvant to a therapy for viral symptoms. In another embodiment, the virus is a respiratory virus.Exemplary viruses targeting the respiratory tract include, but are not limited to, influenza A (e.g., H1N1 and H1N5), influenza B, adenovirus, respiratory syncytial virus (RSV), enterovirus (EV), human rhinovirus (HRV), human metapneumovirus (HMPV), human bocavirus (HBoV), coronaviruses (CoV) (e.g., SARS-CoV-2, SARS-CoV Tor2, and MERS-CoV), and parainfluenza virus (PIV). Exemplary treatments for viral symptoms include, but are not limited to, oseltamivir, zanamivir, ribavirin, pallizumab, and aspirin. In some embodiments, pharmaceutical compositions for treating or preventing the neurological symptoms described herein comprise at least one species (or strain) listed in Table 1 or Table 2, or a mixture listed in Tables 4 through 7. In some embodiments, pharmaceutical compositions for treating or preventing the neurological symptoms described herein comprise strains of Corynebacterium pseudodiphtheriae and optionally strains of Corynebacterium lancifolium. In some embodiments, a method is provided for nasal colonization of at least one pathogenic microorganism for treating a subject, the method comprising the step of administering a pharmaceutical composition to the subject, wherein the pharmaceutical composition comprises Corynebacterium strains listed in Table 1 and Coccidia strains listed in Table 2 or a mixture listed in Tables 4 to 7. In some embodiments, a method is provided for nasal colonization of at least one pathogenic microorganism for treating a subject, the method comprising the step of administering a pharmaceutical composition to the subject, wherein the pharmaceutical composition comprises Corynebacterium pseudodiphtheriae strains listed in Table 1 and Coccidia strains listed in Table 2 or a mixture listed in Tables 4 to 7.
[0040] In some embodiments, this document provides pharmaceutical compositions comprising: a live, purified bacterial population, wherein the live, purified bacterial population includes a variety of Corynebacterium pseudodiphtheriae strains; and a pharmaceutically acceptable excipient. This document further provides a pharmaceutical composition formulated for intranasal administration. This document further provides a pharmaceutical composition formulated for oral administration. This document further provides a pharmaceutical composition in the form of a liquid, solid, semi-solid, or aerosol dosage form. This document further provides a pharmaceutical composition in the form of a suspension, capsule, gel, tablet, lozenge, pill, or powder. This document further provides a pharmaceutical composition wherein the live, purified bacterial population is present in a total quantity of up to 10^15 cfu. This document further provides a pharmaceutical composition wherein the live, purified bacterial population is present in a total quantity of at least 10^3 cfu. This document further provides a pharmaceutical composition wherein the live, purified bacterial population is present in a total quantity of 10^3 to 10^12 cfu. This document further provides a pharmaceutical composition wherein the Corynebacterium pseudodiphtheriae strain is selected from the strains listed in Table 1. This document further provides a pharmaceutical composition wherein the live, purified bacterial population comprises up to 10 strains. In some embodiments, this document provides a method comprising administering the pharmaceutical composition described herein to a subject in need, wherein the subject suffers from respiratory symptoms. This document further provides a method wherein the respiratory symptoms are asthma, COPD, rhinitis, lung cancer, MRSA, pneumonia (including hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), and community-acquired pneumonia (CAP)), or cystic fibrosis. In some embodiments, this document provides use of the pharmaceutical composition described herein in the manufacture of a medicament for treating a subject with asthma, COPD, rhinitis, lung cancer, MRSA (including hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), and community-acquired pneumonia (CAP)), cystic fibrosis, idiopathic pulmonary fibrosis, or interstitial lung disease. In some embodiments, this document provides the use of the pharmaceutical composition described herein in the manufacture of a medicament for treating a subject with Parkinson's disease (PD), iLY body syndrome (iLBD), Lewy body dementia (DLB), Alzheimer's disease (AD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP), frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), pure autonomic failure (PAF), schizophrenia, or Creutzfeldt-Jakob disease (CJD).
[0041] In some embodiments, this document provides pharmaceutical compositions comprising: a live, purified bacterial population, wherein the live, purified bacterial population includes a variety of Corynebacterium species; and a pharmaceutically acceptable excipient. This document further provides a pharmaceutical composition formulated for intranasal administration. This document further provides a pharmaceutical composition formulated for oral administration. This document further provides a pharmaceutical composition in the form of a liquid, solid, semi-solid, or aerosol dosage form. This document further provides a pharmaceutical composition in the form of a suspension, capsule, gel, tablet, lozenge, pill, or powder. This document further provides a pharmaceutical composition wherein the live, purified bacterial population is present in a total amount of up to 10^15 CFU. This document further provides a pharmaceutical composition wherein the live, purified bacterial population is present in a total amount of at least 10^3 CFU. This document further provides a pharmaceutical composition wherein the live, purified bacterial population is present in a total amount of 10^3 to 10^12 CFU. This article further provides a pharmaceutical composition in which the *Corynebacterium* is *Corynebacterium crowdingense*, *Corynebacterium pseudodiphtheriae*, *Corynebacterium propionate*, *Corynebacterium glutamicum*, or *Corynebacterium striatum*. This article further provides a pharmaceutical composition in which the *Corynebacterium* is *Corynebacterium crowdingense*, non-fermenting *Corynebacterium*, ammonia-producing *Corynebacterium*, amycotic acid-producing *Corynebacterium*, silvery-smelling *Corynebacterium*, aquatic *Corynebacterium*, *Corynebacterium auricula*, *Corynebacterium bovis*, *Corynebacterium diphtheriae*, *Corynebacterium equineumoniae* (now *Rhodococcus equi*), effective *Corynebacterium*, *Corynebacterium flavonoids*, glucosinolate-degrading *Corynebacterium*, *Corynebacterium glutamicum*, granulomatous *Corynebacterium*, hemolytic *Corynebacterium*, halophyte *Corynebacterium*, *Corynebacterium kurstii*. The bacteria include *Corynebacterium jejuni*, *Corynebacterium martensii*, *Corynebacterium martensii*, *Corynebacterium microfilii*, *Corynebacterium pustulosa* (Propionibacterium acnes), *Corynebacterium micrometabolicum*, *Corynebacterium propionate*, *Corynebacterium pseudodiphtheriae* (Corynebacterium hoffmannii), *Corynebacterium pseudotuberculosis*, *Corynebacterium sheepii*, *Corynebacterium pyogenes*—*Cryptobacillus pyogenes*, *Corynebacterium urealyticum*, *Corynebacterium nephritis*, *Corynebacterium*, *Corynebacterium striatum*, *Corynebacterium microfilii*, *Corynebacterium ulcerans*, *Corynebacterium urealyticum*, or *Corynebacterium sicca*. This document further provides a pharmaceutical composition wherein the *Corynebacterium* strains are selected from those listed in Table 1. This document further provides a pharmaceutical composition wherein the live, purified bacterial population comprises up to 10 strains. In some embodiments, this document provides a method comprising administering the pharmaceutical composition described herein to a subject in need, wherein the subject suffers from respiratory symptoms.This document further provides a method wherein the respiratory symptoms are asthma, COPD, rhinitis, lung cancer, MRSA, pneumonia (including hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), and community-acquired pneumonia (CAP)), cystic fibrosis, idiopathic pulmonary fibrosis, or interstitial lung disease. In some embodiments, this document provides use of the pharmaceutical composition described herein in the manufacture of a medicament for treating a subject with asthma, COPD, rhinitis, lung cancer, MRSA (including hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), and community-acquired pneumonia (CAP)), cystic fibrosis, idiopathic pulmonary fibrosis, or interstitial lung disease. In some embodiments, this document provides the use of the pharmaceutical composition described herein in the manufacture of a medicament for treating a subject with Parkinson's disease (PD), iLY body syndrome (iLBD), Lewy body dementia (DLB), Alzheimer's disease (AD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP), frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), pure autonomic failure (PAF), schizophrenia, Creutzfeldt-Jakob disease (CJD), or autism spectrum disorder (ASD), post-traumatic stress disorder (PTSD), anxiety disorder, or depression. In some embodiments, ASD is autism, pervasive developmental disorder (PDD-NOS) not otherwise specified, Asperger's syndrome, childhood disintegration disorder (CDD), or Rett syndrome. In some embodiments, anxiety disorder is generalized anxiety disorder, obsessive-compulsive disorder, panic disorder, PTSD, or social phobia.
[0042] In some embodiments, this document provides a pharmaceutical composition comprising: a live, purified bacterial population; and a pharmaceutically acceptable excipient, the live, purified bacterial population comprising multiple strains of *Coccidia laziensis*. This document further provides a pharmaceutical composition formulated for intranasal administration. This document further provides a pharmaceutical composition formulated for oral administration. This document further provides a pharmaceutical composition in the form of a liquid, solid, semi-solid, or aerosol dosage form. This document further provides a pharmaceutical composition in the form of a suspension, capsule, gel, tablet, lozenge, pill, or powder. This document further provides a pharmaceutical composition in which the live, purified bacterial population comprises up to 10 strains. In some embodiments, this document provides a method comprising administering the pharmaceutical composition described herein to a subject in need, wherein the subject suffers from respiratory symptoms. This document further provides a method wherein the respiratory symptoms are asthma, COPD, rhinitis, lung cancer, MRSA, pneumonia (including hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), and community-acquired pneumonia (CAP)), cystic fibrosis, idiopathic pulmonary fibrosis, or interstitial lung disease. In some embodiments, this document provides the use of the pharmaceutical composition described herein in the manufacture of a medicament for treating a subject with asthma, COPD, rhinitis, lung cancer, MRSA, pneumonia (including hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), and community-acquired pneumonia (CAP)), cystic fibrosis, idiopathic pulmonary fibrosis, or interstitial lung disease. In some embodiments, this document provides the use of the pharmaceutical composition described herein in the manufacture of a medicament for treating a subject with Parkinson's disease (PD), iLY body syndrome (iLBD), Lewy body dementia (DLB), Alzheimer's disease (AD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP), frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), pure autonomic failure (PAF), schizophrenia, Creutzfeldt-Jakob disease (CJD), or autism spectrum disorder (ASD), post-traumatic stress disorder (PTSD), anxiety disorder, or depression. In some embodiments, ASD is autism, pervasive developmental disorder (PDD-NOS) not otherwise specified, Asperger's syndrome, childhood disintegration disorder (CDD), or Rett syndrome. In some embodiments, anxiety disorder is generalized anxiety disorder, obsessive-compulsive disorder, panic disorder, PTSD, or social phobia.
[0043] In some embodiments, this document provides a pharmaceutical composition comprising: a live, purified bacterial population, wherein the live, purified bacterial population includes: multiple strains of Corynebacterium pseudodiphtheriae and at least one strain of Coccidia laziensis; and a pharmaceutically acceptable excipient. This document further provides a pharmaceutical composition formulated for intranasal administration. This document further provides a pharmaceutical composition formulated for oral administration. This document further provides a pharmaceutical composition in the form of a liquid, solid, semi-solid, or aerosol dosage form. This document further provides a pharmaceutical composition in the form of a suspension, capsule, gel, tablet, lozenge, pill, or powder. This document further provides a pharmaceutical composition wherein the live, purified bacterial population is present in a total amount of up to 10^15 CFU. This document further provides a pharmaceutical composition wherein the live, purified bacterial population is present in a total amount of at least 10^3 CFU. This document further provides a pharmaceutical composition wherein the live, purified bacterial population is present in a total amount of 10^3 to 10^12 CFU. This document further provides a pharmaceutical composition wherein a strain of *Corynebacterium pseudodiphtheriae* is selected from the strains listed in Table 1. This document further provides a pharmaceutical composition wherein *Coccidioidomyces laziensis* is selected from the strains listed in Table 2. This document further provides a pharmaceutical composition wherein a strain of *Corynebacterium pseudodiphtheriae* is selected from the strains listed in Table 1, and wherein *Coccidioidomyces laziensis* is selected from the strains listed in Table 2. This document further provides a pharmaceutical composition comprising a mixture listed in Tables 4 to 7. This document further provides a pharmaceutical composition wherein the live, purified bacterial population comprises up to 10 strains. In some embodiments, this document provides a method comprising administering the pharmaceutical composition described herein to a subject in need, wherein the subject suffers from respiratory symptoms. This document further provides a method wherein the respiratory symptoms are asthma, COPD, rhinitis, lung cancer, MRSA, pneumonia, cystic fibrosis, idiopathic pulmonary fibrosis, or interstitial lung disease. In some embodiments, this document provides a use of the pharmaceutical composition described herein in the manufacture of a medicament for treating a subject with asthma, COPD, rhinitis, lung cancer, MRSA, pneumonia (including hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), and community-acquired pneumonia (CAP)), cystic fibrosis, idiopathic pulmonary fibrosis, or interstitial lung disease.In some embodiments, this document provides the use of the pharmaceutical composition described herein in the manufacture of a medicament for treating a subject with Parkinson's disease (PD), iLY body syndrome (iLBD), Lewy body dementia (DLB), Alzheimer's disease (AD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP), frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), pure autonomic failure (PAF), schizophrenia, Creutzfeldt-Jakob disease (CJD), or autism, post-traumatic stress disorder (PTSD), anxiety disorder, or depression. In some embodiments, ASD is autism, pervasive developmental disorder (PDD-NOS) not otherwise specified, Asperger's syndrome, childhood disintegration disorder (CDD), or Rett syndrome. In some embodiments, anxiety disorder is generalized anxiety disorder, obsessive-compulsive disorder, panic disorder, post-traumatic stress disorder, or social phobia.
[0044] In some embodiments, this document provides pharmaceutical compositions comprising: a live, purified bacterial population present in a total amount of at least 10^3 cfu; and a pharmaceutically acceptable excipient, wherein the live, purified bacterial population comprises *Corynebacterium pseudodiphtheriae* strains and *Coccidia laziensis* strains, wherein the pharmaceutical composition is formulated for intranasal administration. This document further provides a pharmaceutical composition wherein the live, purified bacterial population is present in a total amount of up to 10^15 cfu. This document further provides a pharmaceutical composition wherein the live, purified bacterial population is present in a total amount of 10^3 to 10^12 cfu. This document further provides a pharmaceutical composition wherein the *Corynebacterium pseudodiphtheriae* strain is selected from the strains listed in Table 1. This document further provides a pharmaceutical composition wherein *Coccidia laziensis* is selected from the strains listed in Table 2. This document further provides a pharmaceutical composition wherein the *Corynebacterium pseudodiphtheriae* strain is selected from the strains listed in Table 1, and wherein *Coccidia laziensis* is selected from the strains listed in Table 2. This document further provides pharmaceutical compositions comprising mixtures listed in Tables 4 to 7. This document further provides a pharmaceutical composition wherein the live, purified bacterial population comprises up to 10 strains. In some embodiments, this document provides a method comprising administering the pharmaceutical composition described herein to a subject in need, wherein the subject suffers from respiratory symptoms. This document further provides a method wherein the respiratory symptoms are asthma, COPD, rhinitis, lung cancer, MRSA, pneumonia (including hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), and community-acquired pneumonia (CAP)), cystic fibrosis, idiopathic pulmonary fibrosis, or interstitial lung disease. In some embodiments, this document provides use of the pharmaceutical composition described herein in the manufacture of a medicament for treating a subject with asthma, COPD, rhinitis, lung cancer, MRSA, pneumonia (including hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), and community-acquired pneumonia (CAP)) or cystic fibrosis, idiopathic pulmonary fibrosis, or interstitial lung disease. In some embodiments, this document provides the use of the pharmaceutical composition described herein in the manufacture of a medicament for treating a subject with Parkinson's disease (PD), iLY body syndrome (iLBD), Lewy body dementia (DLB), Alzheimer's disease (AD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP), frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), pure autonomic failure (PAF), schizophrenia, or Creutzfeldt-Jakob disease (CJD).
[0045] In some embodiments, this document provides pharmaceutical compositions comprising: a live, purified bacterial population present in a total amount of at least 10^3 CFU; and a pharmaceutically acceptable excipient, wherein the live, purified bacterial population includes strains of *Corynebacterium pseudodiphtheriae* and *Coccidia laziensis*, wherein the pharmaceutical composition is formulated for oral administration. This document further provides a pharmaceutical composition wherein the live, purified bacterial population is present in a total amount of up to 10^15 CFU. This document further provides a pharmaceutical composition wherein the live, purified bacterial population is present in a total amount of at least 10^3 CFU. This document further provides a pharmaceutical composition wherein the live, purified bacterial population is present in a total amount of 10^3 to 10^12 CFU. This document further provides a pharmaceutical composition wherein the *Corynebacterium pseudodiphtheriae* strain is selected from the strains listed in Table 1. This document further provides a pharmaceutical composition wherein *Coccidia laziensis* is selected from the strains listed in Table 2. This document further provides a pharmaceutical composition wherein the *Corynebacterium pseudodiphtheriae* strain is selected from the strains listed in Table 1, and wherein *Coccidia laziensis* is selected from the strains listed in Table 2. This document further provides pharmaceutical compositions comprising mixtures listed in Tables 4 to 7. This document further provides a pharmaceutical composition wherein the live, purified bacterial population comprises up to 10 strains. In some embodiments, this document provides a method comprising administering the pharmaceutical composition described herein to a subject in need, wherein the subject suffers from respiratory symptoms. This document further provides a method wherein the respiratory symptoms are asthma, COPD, rhinitis, lung cancer, MRSA, pneumonia (including hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), and community-acquired pneumonia (CAP)), cystic fibrosis, idiopathic pulmonary fibrosis, or interstitial lung disease. In some embodiments, this document provides use of the pharmaceutical composition described herein in the manufacture of a medicament for treating a subject with asthma, COPD, rhinitis, lung cancer, MRSA, pneumonia (including hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), and community-acquired pneumonia (CAP)) or cystic fibrosis, idiopathic pulmonary fibrosis, or interstitial lung disease. In some embodiments, this document provides the use of the pharmaceutical composition described herein in the manufacture of a medicament for the treatment of Parkinson's disease (PD), iLY body syndrome (iLBD), Lewy body dementia (DLB), Alzheimer's disease (AD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP), frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), pure autonomic failure (PAF), schizophrenia, Creutzfeldt-Jakob disease (CJD) or autism spectrum disorder (ASD), post-traumatic stress disorder (PTSD), anxiety disorder, or depression.In some embodiments, ASD is autism, pervasive developmental disorder (PDD-NOS) without further designation, Asperger's syndrome, childhood disintegration disorder (CDD), or Rett syndrome. In some embodiments, anxiety disorder is generalized anxiety disorder, obsessive-compulsive disorder, panic disorder, post-traumatic stress disorder, or social phobia.
[0046] In some embodiments, this document provides a method for microbiome modification of a subject, the method comprising administering to a subject in need: a purified, live bacterial population, the purified, live bacterial population comprising at least one bacterial strain present in an amount sufficient to prevent or treat lung symptoms, wherein the at least one bacterial strain is isolated from the upper respiratory tract of a donor. In some embodiments, this document provides a method for treating inflammatory lung symptoms, the method comprising administering to a subject suffering from inflammatory lung symptoms: a purified, live bacterial population, the purified, live bacterial population comprising at least one bacterial strain present in an amount sufficient to reduce the incidence of pathogen colonization in the nasal cavity, wherein the at least one bacterial strain is isolated from the upper respiratory tract of a donor. This document further provides a method wherein the pathogenic bacteria include Staphylococcus aureus, Streptococcus pneumoniae, or Pseudomonas aeruginosa. This document further provides a method wherein the pathogenic bacteria are strains listed in Table 3. In some embodiments, this document provides a method for treating airway inflammatory symptoms, the method comprising: administering to a subject in need a live, purified bacterial population, wherein the live, purified bacterial population comprises: multiple strains of *Corynebacterium pseudodiphtheriae*; and at least one strain of *Coccidioidomyces laziensis*. This document further provides a method wherein the *Corynebacterium pseudodiphtheriae* strain is selected from the strains listed in Table 1. This document further provides a method wherein *Coccidioidomyces laziensis* is selected from the strains listed in Table 2. This document further provides a pharmaceutical composition comprising mixtures listed in Tables 4 to 7. This document further provides a method wherein the *Corynebacterium pseudodiphtheriae* strain is selected from the strains listed in Table 1, and wherein *Coccidioidomyces laziensis* is selected from the strains listed in Table 2. This document further provides a method wherein the airway inflammatory symptoms are asthma, COPD, rhinitis, MRSA, pneumonia (including hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), and community-acquired pneumonia (CAP)), cystic fibrosis, idiopathic pulmonary fibrosis, or interstitial lung disease. This document further provides a method wherein the bacterial population is administered intranasally. This article further provides a method in which the bacterial population is administered orally. This article further provides a method in which the subject is an infant. This article further provides a method in which the subject is a child. This article further provides a method in which the subject is an adult. This article further provides a method in which the live, purified bacterial population is present in a total quantity of up to 10^15 cfu. This article further provides a method in which the live, purified bacterial population is present in a total quantity of 10^3 to 10^12 cfu.
[0047] In some embodiments, this document provides a method for treating lower respiratory tract symptoms, the method comprising: administering to a subject suffering from a lower respiratory tract infection a live, purified bacterial population, wherein the live, purified bacterial population includes: *Corynebacterium pseudodiphtheriae* strains; and *Coccidioidomyces laziensis* strains. In some embodiments, this document provides a method for treating airway inflammatory symptoms, the method comprising: administering to a subject in need a live, purified bacterial population, wherein the live, purified bacterial population includes: multiple *Corynebacterium pseudodiphtheriae* strains; and at least one *Coccidioidomyces laziensis* strain. This document further provides a method wherein the *Corynebacterium pseudodiphtheriae* strain is selected from the strains listed in Table 1. This document further provides a method wherein *Coccidioidomyces laziensis* is selected from the strains listed in Table 2. This document further provides a method wherein the *Corynebacterium pseudodiphtheriae* strain is selected from the strains listed in Table 1, and wherein *Coccidioidomyces laziensis* is selected from the strains listed in Table 2. This document further provides pharmaceutical compositions comprising mixtures listed in Tables 4 to 7. This article further provides a method in which the airway inflammatory condition is asthma, COPD, rhinitis, MRSA, pneumonia (including hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), and community-acquired pneumonia (CAP)), cystic fibrosis, idiopathic pulmonary fibrosis, or interstitial lung disease. This article further provides a method in which the live, purified bacterial population is administered intranasally. This article further provides a method in which the live, purified bacterial population is administered orally. This article further provides a method in which the subject is an infant. This article further provides a method in which the subject is a child. This article further provides a method in which the subject is an adult. This article further provides a method in which the live, purified bacterial population is present in a total quantity of up to 10^15 cfu. This article further provides a method in which the live, purified bacterial population is present in a total quantity of 10^3 to 10^12 cfu.
[0048] In some embodiments, this document provides a method for treating airway inflammatory symptoms, the method comprising: administering to a subject suffering from airway inflammatory symptoms a live, purified bacterial population, wherein the live, purified bacterial population includes a variety of Corynebacterium species. This document further provides a method wherein the Corynebacterium species are *Corynebacterium clausti*, *Corynebacterium nonfermentatum*, *Corynebacterium ammoniagenicum*, *Corynebacterium amylopectinum*, *Corynebacterium aureum*, *Corynebacterium aquaticum*, *Corynebacterium otrum*, *Corynebacterium bovis*, *Corynebacterium diphtheriae*, *Corynebacterium equineumoniae* (now *Rhodococcus equi*), *Corynebacterium viabilityense*, *Corynebacterium flavonoids*, *Corynebacterium glucoside*, *Corynebacterium glutamicum*, *Corynebacterium granulomatum*, *Corynebacterium hemolyticum*, *Corynebacterium halophyte*, and *Corynebacterium kurstii*. The bacteria include *Corynebacterium jejuni*, *Corynebacterium medroxyn*, *Corynebacterium martensii*, *Corynebacterium microfilii*, *Corynebacterium pustulosa* (Propionibacterium acnes), *Corynebacterium micrometabolicum*, *Corynebacterium propionate*, *Corynebacterium pseudodiphtheriae* (Corynebacterium hoffmannii), *Corynebacterium pseudotuberculosis*, *Corynebacterium sheepii*, *Corynebacterium pyogenes*—*Cryptobacillus pyogenes*, *Corynebacterium urealyticum*, *Corynebacterium nephritis*, *Corynebacterium*, *Corynebacterium striatum*, *Corynebacterium microfilii*, *Corynebacterium ulcerans*, *Corynebacterium urealyticum*, or *Corynebacterium sicca*. In some embodiments, this document provides a method for treating inflammatory symptoms of the airways, the method comprising: administering to a subject in need a live, purified bacterial population, wherein the live, purified bacterial population includes: multiple strains of *Corynebacterium pseudodiphtheriae*; and at least one strain of *Corynebacterium laziness*. This document further provides a method wherein the *Corynebacterium pseudodiphtheriae* strain is selected from the strains listed in Table 1. This document further provides a method wherein *Corynebacterium laziness* is selected from the strains listed in Table 2. This article further provides a method wherein the *Corynebacterium pseudodiphtheriae* strain is selected from the strains listed in Table 1, and wherein *Coccidioidomyces laziensis* is selected from the strains listed in Table 2. This article further provides a pharmaceutical composition comprising mixtures listed in Tables 4 to 7. This article further provides a method wherein the airway inflammatory condition is asthma, COPD, rhinitis, MRSA, pneumonia (including hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), and community-acquired pneumonia (CAP)), cystic fibrosis, idiopathic pulmonary fibrosis, or interstitial lung disease. This article further provides a method wherein the live, purified bacterial population is administered intranasally. This article further provides a method wherein the live, purified bacterial population is administered orally. This article further provides a method wherein the subject is an infant. This article further provides a method wherein the subject is a child. This article further provides a method wherein the subject is an adult. This article further provides a method wherein the live, purified bacterial population is present in a total amount of up to 10^15 cfu. This paper further provides a method in which the live, purified bacterial population exists in a total amount of 10^3 cfu to 10^12 cfu.
[0049] In some embodiments, this document provides a method for treating airway inflammatory symptoms, the method comprising: administering to a subject suffering from airway inflammatory symptoms a live, purified bacterial population, wherein the live, purified bacterial population comprises: multiple strains of *Coccidia laziensis*. In some embodiments, this document provides a method for treating airway inflammatory symptoms, the method comprising: administering to a subject in need a live, purified bacterial population, wherein the live, purified bacterial population comprises: multiple strains of *Corynebacterium pseudodiphtheriae*; and at least one strain of *Coccidia laziensis*. This document further provides a method wherein the *Corynebacterium pseudodiphtheriae* strain is selected from the strains listed in Table 1. This document further provides a method wherein *Coccidia laziensis* is selected from the strains listed in Table 2. This document further provides a method wherein the *Corynebacterium pseudodiphtheriae* strain is selected from the strains listed in Table 1, and wherein *Coccidia laziensis* is selected from the strains listed in Table 2. This article further provides a method in which the airway inflammatory condition is asthma, COPD, rhinitis, MRSA, pneumonia (including hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), and community-acquired pneumonia (CAP)), cystic fibrosis, idiopathic pulmonary fibrosis, or interstitial lung disease. This article further provides a method in which the live, purified bacterial population is administered intranasally. This article further provides a method in which the live, purified bacterial population is administered orally. This article further provides a method in which the subject is an infant. This article further provides a method in which the subject is a child. This article further provides a method in which the subject is an adult. This article further provides a method in which the live, purified bacterial population is present in a total quantity of up to 10^15 cfu. This article further provides a method in which the live, purified bacterial population is present in a total quantity of 10^3 to 10^12 cfu.
[0050] In some embodiments, this document provides a method for treating lung cancer, the method comprising: administering to a subject suffering from lung cancer a live, purified bacterial population, wherein the live, purified bacterial population comprises: a bacterial population of at least one Corynebacterium, optionally at least one Corynebacterium pseudodiphtheriae strain; and optionally at least one Corynebacterium laziness strain. This document further provides a method wherein the Corynebacterium is *Corynebacterium bulgaricum*, *Corynebacterium nonfermentatum*, *Corynebacterium ammoniagenicum*, *Corynebacterium amylopectinum*, *Corynebacterium aureum*, *Corynebacterium aquaticum*, *Corynebacterium auriculatum*, *Corynebacterium bovis*, *Corynebacterium diphtheriae*, *Corynebacterium equineumoniae* (now *Rhodococcus equine*), *Corynebacterium viabilityense*, *Corynebacterium flavonoids*, *Corynebacterium glucoside*, *Corynebacterium glutamicum*, *Corynebacterium granulomatum*, *Corynebacterium hemolyticum*, *Corynebacterium halophyte*, *Corynebacterium kurstii*. The bacteria include *Corynebacterium jejuni*, *Corynebacterium medroxyn*, *Corynebacterium martensii*, *Corynebacterium microfilii*, *Corynebacterium pustulosa* (Propionibacterium acnes), *Corynebacterium micrometabolicum*, *Corynebacterium propionate*, *Corynebacterium pseudodiphtheriae* (Corynebacterium hoffmannii), *Corynebacterium pseudotuberculosis*, *Corynebacterium sheepii*, *Corynebacterium pyogenes*—*Cryptobacillus pyogenes*, *Corynebacterium urealyticum*, *Corynebacterium nephritis*, *Corynebacterium*, *Corynebacterium striatum*, *Corynebacterium microfilii*, *Corynebacterium ulcerans*, *Corynebacterium urealyticum*, or *Corynebacterium sicca*. This document further provides a method wherein the *Corynebacterium pseudodiphtheriae* strain is selected from the strains listed in Table 1. This document further provides a method wherein *Coccidioidomyces laziensis* is selected from the strains listed in Table 2. This document further provides a method wherein the *Corynebacterium pseudodiphtheriae* strain is selected from the strains listed in Table 1, and wherein *Coccidioidomyces laziensis* is selected from the strains listed in Table 2. This document further provides a pharmaceutical composition comprising mixtures listed in Tables 4 to 7. This document further provides a method wherein the live, purified bacterial population is administered intranasally. This article further provides a method in which the live, purified bacterial population is administered orally. This article further provides a method in which the subject is an infant. This article further provides a method in which the subject is a child. This article further provides a method in which the subject is an adult. This article further provides a method in which the live, purified bacterial population is present in a total quantity of up to 10^15 cfu. This article further provides a method in which the live, purified bacterial population is present in a total quantity of 10^3 to 10^12 cfu.
[0051] In some embodiments, this document provides a method for treating cancer, the method comprising: administering to a subject suffering from cancer a live, purified bacterial population as adjuvant therapy, wherein the live, purified bacterial population comprises: a bacterial population of at least one Corynebacterium, optionally at least one Corynebacterium pseudodiphtheriae strain; and optionally at least one Corynebacterium laziness strain. This document further provides a method wherein the Corynebacterium is *Corynebacterium bulgaricum*, *Corynebacterium nonfermentatum*, *Corynebacterium ammoniagenicum*, *Corynebacterium amylopectinum*, *Corynebacterium aureum*, *Corynebacterium aquaticum*, *Corynebacterium otolactum*, *Corynebacterium diphtheriae*, *Corynebacterium equineumoniae* (now *Rhodococcus equine*), *Corynebacterium viabilityense*, *Corynebacterium flavonoids*, *Corynebacterium glucoside*, *Corynebacterium glutamicum*, *Corynebacterium granulomatum*, *Corynebacterium hemolyticum*, *Corynebacterium halophyte*, *Corynebacterium kurstii*. The text describes a series of bacteria, including *Corynebacterium jejuni*, *Corynebacterium medroxysum*, *Corynebacterium martensii*, *Corynebacterium microfiliis*, *Corynebacterium pustulosa* (Propionibacterium acnes), *Corynebacterium micrometabolicum*, *Corynebacterium propionate*, *Corynebacterium pseudodiphtheriae* (Corynebacterium hoffmannii), *Corynebacterium pseudotuberculosis*, *Corynebacterium sheepii*, *Corynebacterium pyogenes*—*Cryptobacillus pyogenes*, *Corynebacterium urealyticum*, *Corynebacterium nephritis*, *Corynebacterium*, *Corynebacterium striatum*, *Corynebacterium microfiliis*, *Corynebacterium ulcerans*, *Corynebacterium urealyticum*, or *Corynebacterium sicca*. The text further provides a method in which a strain of *Corynebacterium pseudodiphtheriae* is selected from the strains listed in Table 1. It also provides a method in which *Coccidioidomyces laziensis* is selected from the strains listed in Table 2. Finally, it provides a method in which a strain of *Corynebacterium pseudodiphtheriae* is selected from the strains listed in Table 1, and *Coccidioidomyces laziensis* is selected from the strains listed in Table 2. The text also provides a pharmaceutical composition comprising mixtures listed in Tables 4 to 7. Finally, it provides a method in which the cancer is a solid tumor or a hematopoietic system cancer. This article further provides a method wherein the solid cancer is carcinoma or sarcoma. This article further provides a method wherein the hematopoietic system cancer is leukemia, myeloma, or lymphoma. This article further provides a method wherein the adjuvant therapy is chemotherapy, radiation therapy, or checkpoint inhibitor therapy. This article further provides a method wherein the live, purified bacterial population is administered before or after the administration of the chemotherapy, radiation therapy, or checkpoint inhibitor therapy. This article further provides a method wherein the live, purified bacterial population is administered intranasally. This article further provides a method wherein the live, purified bacterial population is administered orally. This article further provides a method wherein the subject is an infant. This article further provides a method wherein the subject is a child. This article further provides a method wherein the subject is an adult. This article further provides a method wherein the live, purified bacterial population is present in a total amount of up to 10^15 cfu.This paper further provides a method in which the live, purified bacterial population exists in a total amount of 10^3 cfu to 10^12 cfu.
[0052] In some embodiments, this document provides a method for treating asthma, the method comprising: administering to a subject suffering from asthma a live, purified bacterial population, wherein the live, purified bacterial population comprises: a bacterial population of at least one Corynebacterium, optionally at least one Corynebacterium pseudodiphtheriae strain; and optionally at least one Corynebacterium laziness strain. This document further provides a method wherein the Corynebacterium is *Corynebacterium bulgaricum*, *Corynebacterium nonfermentatum*, *Corynebacterium ammoniagenicum*, *Corynebacterium amylopectinum*, *Corynebacterium aureum*, *Corynebacterium aquaticum*, *Corynebacterium otum*, *Corynebacterium bovis*, *Corynebacterium diphtheriae*, *Corynebacterium equineumoniae* (now *Rhodococcus equine*), *Corynebacterium viabilityense*, *Corynebacterium flavonoids*, *Corynebacterium glucoside*, *Corynebacterium glutamicum*, *Corynebacterium granulomatum*, *Corynebacterium hemolyticum*, *Corynebacterium halophyte*, *Corynebacterium kurstii*. The bacteria include *Corynebacterium jejuni*, *Corynebacterium medroxyn*, *Corynebacterium martensii*, *Corynebacterium microfilii*, *Corynebacterium pustulosa* (Propionibacterium acnes), *Corynebacterium micrometabolicum*, *Corynebacterium propionate*, *Corynebacterium pseudodiphtheriae* (Corynebacterium hoffmannii), *Corynebacterium pseudotuberculosis*, *Corynebacterium sheepii*, *Corynebacterium pyogenes*—*Cryptobacillus pyogenes*, *Corynebacterium urealyticum*, *Corynebacterium nephritis*, *Corynebacterium*, *Corynebacterium striatum*, *Corynebacterium microfilii*, *Corynebacterium ulcerans*, *Corynebacterium urealyticum*, or *Corynebacterium sicca*. This document further provides a method wherein the *Corynebacterium pseudodiphtheriae* strain is selected from the strains listed in Table 1. This document further provides a method wherein *Coccidioidomyces laziensis* is selected from the strains listed in Table 2. This document further provides a method wherein the *Corynebacterium pseudodiphtheriae* strain is selected from the strains listed in Table 1, and wherein *Coccidioidomyces laziensis* is selected from the strains listed in Table 2. This document further provides a pharmaceutical composition comprising mixtures listed in Tables 4 to 7. This document further provides a method wherein the live, purified bacterial population is administered intranasally. This article further provides a method in which the live, purified bacterial population is administered orally. This article further provides a method in which the subject is an infant. This article further provides a method in which the subject is a child. This article further provides a method in which the subject is an adult. This article further provides a method in which the live, purified bacterial population is present in a total quantity of up to 10^15 cfu. This article further provides a method in which the live, purified bacterial population is present in a total quantity of 10^3 to 10^12 cfu.
[0053] In some embodiments, this document provides a method for treating symptoms of a viral infection, the method comprising: administering to a subject suffering from a viral infection a live, purified bacterial population, wherein the live, purified bacterial population comprises: a bacterial population of at least one Corynebacterium, optionally at least one Corynebacterium pseudodiphtheriae strain; and optionally at least one Corynebacterium laziness strain. This document further provides a method wherein the Corynebacterium is *Corynebacterium bulgaricum*, *Corynebacterium nonfermentatum*, *Corynebacterium ammoniagenicum*, *Corynebacterium amylopectinum*, *Corynebacterium aureum*, *Corynebacterium auriculatum*, *Corynebacterium bovis*, *Corynebacterium diphtheriae*, *Corynebacterium equineumoniae* (now *Rhodococcus equine*), *Corynebacterium viableum*, *Corynebacterium flavonoids*, *Corynebacterium glucoside*, *Corynebacterium glutamicum*, *Corynebacterium granulomatum*, *Corynebacterium hemolyticum*, *Corynebacterium halophyte*, *Corynebacterium kurstii*. The present invention relates to the following strains of Corynebacterium jejuni, Corynebacterium medricularis, Corynebacterium martensii, Corynebacterium microfiliis, Corynebacterium pustulosa (Propionibacterium acnes), Corynebacterium micrometabolicum, Corynebacterium propionate, Corynebacterium pseudodiphtheriae (Corynebacterium hoffmannii), Corynebacterium pseudotuberculosis, Corynebacterium sheepii, Corynebacterium pyogenes—Cryptospirosis, Corynebacterium urealyticum, Corynebacterium nephrostomyense, Corynebacterium, Corynebacterium striatum, Corynebacterium microfiliis, Corynebacterium ulcerans, Corynebacterium urealyticum, or Corynebacterium sicca. The present invention further provides a method wherein the Corynebacterium pseudodiphtheriae strain is selected from the strains listed in Table 1. The present invention further provides a method wherein *Coccidioidomyces laziensis* is selected from the strains listed in Table 2. The present invention further provides a method wherein the Corynebacterium pseudodiphtheriae strain is selected from the strains listed in Table 1, and wherein *Coccidioidomyces laziensis* is selected from the strains listed in Table 2. The present invention further provides a pharmaceutical composition comprising mixtures listed in Tables 4 to 7. This article further provides a method wherein the viral infection is influenza A, influenza B, adenovirus, respiratory syncytial virus (RSV), enterovirus (EVs), human rhinovirus (HRV), human metapneumovirus (HMPV), human bocavirus (HBoV), coronavirus (CoV), or parainfluenza virus (PIV). This article further provides a method wherein the live, purified bacterial population is administered intranasally. This article further provides a method wherein the live, purified bacterial population is administered orally. This article further provides a method wherein the subject is an infant. This article further provides a method wherein the subject is a child. This article further provides a method wherein the subject is an adult. This article further provides a method wherein the live, purified bacterial population is present in a total quantity of up to 10^15 cfu. This article further provides a method wherein the live, purified bacterial population is present in a total quantity of 10^3 to 10^12 cfu.
[0054] In some embodiments, this document provides a method for treating idiopathic pulmonary fibrosis, the method comprising: administering to a subject suffering from idiopathic pulmonary fibrosis a live, purified bacterial population, wherein the live, purified bacterial population comprises: a bacterial population of at least one Corynebacterium, optionally at least one Corynebacterium pseudodiphtheriae strain; and optionally at least one Corynebacterium laziness strain. This document further provides a method wherein the Corynebacterium is *Corynebacterium clausti*, *Corynebacterium nonfermentatum*, *Corynebacterium ammoniagenicum*, *Corynebacterium amylopectinum*, *Corynebacterium aquaticum*, *Corynebacterium auriculatum*, *Corynebacterium bovis*, *Corynebacterium diphtheriae*, *Corynebacterium equineumoniae* (now *Rhodococcus equine*), *Corynebacterium viabilityense*, *Corynebacterium flavonoids*, *Corynebacterium glucoside*, *Corynebacterium glutamicum*, *Corynebacterium granulomatum*, *Corynebacterium hemolyticum*, *Corynebacterium halophyte*, *Corynebacterium kurstii*. The bacteria include *Corynebacterium jejuni*, *Corynebacterium medroxysum*, *Corynebacterium martensii*, *Corynebacterium microfilii*, *Corynebacterium pustulosa* (Propionibacterium acnes), *Corynebacterium micrometabolicum*, *Corynebacterium propionate*, *Corynebacterium pseudodiphtheriae* (Corynebacterium hoffmannii), *Corynebacterium pseudotuberculosis*, *Corynebacterium sheepii*, *Corynebacterium pyogenes*—*Cryptobacillus pyogenes*, *Corynebacterium urealyticum*, *Corynebacterium nephritis*, *Corynebacterium*, *Corynebacterium striatum*, *Corynebacterium microfilii*, *Corynebacterium ulcerans*, *Corynebacterium urealyticum*, or *Corynebacterium sicca*. This document further provides a method wherein the *Corynebacterium pseudodiphtheriae* strain is selected from the strains listed in Table 1. This document further provides a method wherein *Coccidioidomyces laziensis* is selected from the strains listed in Table 2. This document further provides a method wherein the *Corynebacterium pseudodiphtheriae* strain is selected from the strains listed in Table 1, and wherein *Coccidioidomyces laziensis* is selected from the strains listed in Table 2. This document further provides a pharmaceutical composition comprising mixtures listed in Tables 4 to 7. This document further provides a method wherein the bacterial population is administered intranasally. This article further provides a method in which the live, purified bacterial population is administered orally. This article further provides a method in which the subject is an infant. This article further provides a method in which the subject is a child. This article further provides a method in which the subject is an adult. This article further provides a method in which the live, purified bacterial population is present in a total quantity of up to 10^15 cfu. This article further provides a method in which the live, purified bacterial population is present in a total quantity of 10^3 to 10^12 cfu.
[0055] In some embodiments, this document provides a method for treating MRSA, the method comprising: administering intranasal or oral administration of a live, purified bacterial population to a subject suffering from MRSA (MRSA positive), wherein the live, purified bacterial population comprises: a bacterial population of at least one Corynebacterium, optionally at least one Corynebacterium pseudodiphtheriae strain; and at least one Corynebacterium laziness strain. This document further provides a method wherein the Corynebacterium is *Corynebacterium bulgaricum*, *Corynebacterium nonfermentatum*, *Corynebacterium ammoniagenicum*, *Corynebacterium amylopectinum*, *Corynebacterium aureum*, *Corynebacterium aquaticum*, *Corynebacterium otum*, *Corynebacterium bovis*, *Corynebacterium diphtheriae*, *Corynebacterium equineumoniae* (now *Rhodococcus equine*), *Corynebacterium viabilityense*, *Corynebacterium flavonoids*, *Corynebacterium glucoside*, *Corynebacterium glutamicum*, *Corynebacterium granulomatum*, *Corynebacterium hemolyticum*, *Corynebacterium halophyte*, *Corynebacterium kurstii*. The present invention relates to the following bacteria: *Corynebacterium jejuni*, *Corynebacterium medricularis*, *Corynebacterium martensii*, *Corynebacterium malformatum*, *Corynebacterium pustulosa*, *Corynebacterium micrometabolicum*, *Corynebacterium propionate*, *Corynebacterium pseudodiphtheriae* (*Corynebacterium hoffmannii*), *Corynebacterium pseudotuberculosis*, *Corynebacterium sheepii*, *Corynebacterium pyogenes*—*Cryptobacillus pyogenes*, *Corynebacterium urealyticum*, *Corynebacterium nephritis*, *Corynebacterium*, *Corynebacterium striatum*, *Corynebacterium microphyllum*, *Corynebacterium ulcerans*, *Corynebacterium urealyticum*, or *Corynebacterium sicca*. This invention further provides a method wherein the *Corynebacterium pseudodiphtheriae* strain is selected from the strains listed in Table 1. This invention further provides a method wherein *Coccidioidomyces laziensis* is selected from the strains listed in Table 2. This invention further provides a method wherein the *Corynebacterium pseudodiphtheriae* strain is selected from the strains listed in Table 1, and wherein *Coccidioidomyces laziensis* is selected from the strains listed in Table 2. This invention further provides a pharmaceutical composition comprising mixtures listed in Tables 4 to 7. This invention further provides a method wherein the subject is an infant. This paper further provides a method in which the subject is a child. This paper further provides a method in which the subject is an adult. This paper further provides a method in which the live, purified bacterial population is present in a total quantity of up to 10^15 CFU. This paper further provides a method in which the live, purified bacterial population is present in a total quantity of 10^3 CFU to 10^12 CFU.
[0056] In some embodiments, this document provides a method for treating MSSA, the method comprising: administering intranasal or oral administration of a live, purified bacterial population to a subject suffering from MSSA (MSSA positive), wherein the live, purified bacterial population comprises: a bacterial population of at least one Corynebacterium, optionally at least one Corynebacterium pseudodiphtheriae strain; and at least one Corynebacterium laziness strain. This document further provides a method wherein the Corynebacterium is *Corynebacterium bulgaricum*, *Corynebacterium nonfermentatum*, *Corynebacterium amyloliquefaciens*, *Corynebacterium amyloliquefaciens*, *Corynebacterium aureum*, *Corynebacterium auriculatum*, *Corynebacterium bovis*, *Corynebacterium diphtheriae*, *Corynebacterium equineumoniae* (now *Rhodococcus equine*), *Corynebacterium viabilityense*, *Corynebacterium flavonoids*, *Corynebacterium glucoside*, *Corynebacterium glutamicum*, *Corynebacterium granulomatum*, *Corynebacterium hemolyticum*, *Corynebacterium halophyte*, *Corynebacterium kurstii*. The present invention relates to the following bacteria: *Corynebacterium jejuni*, *Corynebacterium medricularis*, *Corynebacterium martensii*, *Corynebacterium malformatum*, *Corynebacterium pustulosa*, *Corynebacterium micrometabolicum*, *Corynebacterium propionate*, *Corynebacterium pseudodiphtheriae* (*Corynebacterium hoffmannii*), *Corynebacterium pseudotuberculosis*, *Corynebacterium sheepii*, *Corynebacterium pyogenes*—*Cryptobacillus pyogenes*, *Corynebacterium urealyticum*, *Corynebacterium nephritis*, *Corynebacterium*, *Corynebacterium striatum*, *Corynebacterium microphyllum*, *Corynebacterium ulcerans*, *Corynebacterium urealyticum*, or *Corynebacterium sicca*. This invention further provides a method wherein the *Corynebacterium pseudodiphtheriae* strain is selected from the strains listed in Table 1. This invention further provides a method wherein *Coccidioidomyces laziensis* is selected from the strains listed in Table 2. This invention further provides a method wherein the *Corynebacterium pseudodiphtheriae* strain is selected from the strains listed in Table 1, and wherein *Coccidioidomyces laziensis* is selected from the strains listed in Table 2. This invention further provides a pharmaceutical composition comprising mixtures listed in Tables 4 to 7. This invention further provides a method wherein the subject is an infant. This paper further provides a method in which the subject is a child. This paper further provides a method in which the subject is an adult. This paper further provides a method in which the live, purified bacterial population is present in a total quantity of up to 10^15 CFU. This paper further provides a method in which the live, purified bacterial population is present in a total quantity of 10^3 CFU to 10^12 CFU.
[0057] In some embodiments, this document provides a method for treating pneumonia, the method comprising: administering intranasal or oral administration to a subject suffering from pneumonia a live, purified bacterial population present in an amount of at least 10^3 cfu, wherein the live, purified bacterial population comprises: a bacterial population of at least one Corynebacterium, optionally at least one Corynebacterium pseudodiphtheriae strain; and at least one Corynebacterium laziness strain. This document further provides a method wherein the Corynebacterium is *Corynebacterium bulgaricum*, *Corynebacterium nonfermentatum*, *Corynebacterium ammoniagenicum*, *Corynebacterium amylopectinum*, *Corynebacterium aureum*, *Corynebacterium aquaticum*, *Corynebacterium otolactum*, *Corynebacterium bovis*, *Corynebacterium diphtheriae*, *Corynebacterium equineumoniae* (now *Rhodococcus equine*), *Corynebacterium viabilityense*, *Corynebacterium flavonoids*, *Corynebacterium glucoside*, *Corynebacterium glutamicum*, *Corynebacterium granulomatum*, *Corynebacterium hemolyticum*, *Corynebacterium halophyte*, *Corynebacterium kurstii*. The present invention relates to the following bacteria: *Corynebacterium jejuni*, *Corynebacterium medricularis*, *Corynebacterium martensii*, *Corynebacterium malformatum*, *Corynebacterium pustulosa*, *Corynebacterium micrometabolicum*, *Corynebacterium propionate*, *Corynebacterium pseudodiphtheriae* (*Corynebacterium hoffmannii*), *Corynebacterium pseudotuberculosis*, *Corynebacterium sheepii*, *Corynebacterium pyogenes*—*Cryptobacillus pyogenes*, *Corynebacterium urealyticum*, *Corynebacterium nephritis*, *Corynebacterium*, *Corynebacterium striatum*, *Corynebacterium microphyllum*, *Corynebacterium ulcerans*, *Corynebacterium urealyticum*, or *Corynebacterium sicca*. This invention further provides a method wherein the *Corynebacterium pseudodiphtheriae* strain is selected from the strains listed in Table 1. This invention further provides a method wherein *Coccidioidomyces laziensis* is selected from the strains listed in Table 2. This invention further provides a method wherein the *Corynebacterium pseudodiphtheriae* strain is selected from the strains listed in Table 1, and wherein *Coccidioidomyces laziensis* is selected from the strains listed in Table 2. This invention further provides a pharmaceutical composition comprising mixtures listed in Tables 4 to 7. This invention further provides a method wherein the subject is an infant. This article further provides a method in which the subject is a child. This article further provides a method in which the subject is an adult. This article further provides a method in which the live, purified bacterial population is present in a total quantity of up to 10^15 cfu. This article further provides a method in which the live, purified bacterial population is present in a total quantity of 10^3 to 10^12 cfu. This article further provides a method in which the pneumonia is hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), or community-acquired pneumonia (CAP).
[0058] In some embodiments, this document provides a method for treating rhinitis, the method comprising: administering to a subject suffering from rhinitis a live, purified bacterial population, wherein the live, purified bacterial population comprises: a bacterial population of at least one Corynebacterium, optionally at least one Corynebacterium pseudodiphtheriae strain; and optionally at least one Corynebacterium laziness strain. This document further provides a method wherein the rhinitis is allergic rhinitis or non-allergic rhinitis. This document further provides a method wherein the Corynebacterium is *Corynebacterium clausti*, *Corynebacterium nonfermentatum*, *Corynebacterium ammoniagenicum*, *Corynebacterium amylopectinum*, *Corynebacterium aureum*, *Corynebacterium aquaticum*, *Corynebacterium otolactum*, *Corynebacterium bovis*, *Corynebacterium diphtheriae*, *Corynebacterium equineumoniae* (now *Rhodococcus equine*), *Corynebacterium viabilityense*, *Corynebacterium flavonoids*, *Corynebacterium glucoside*, *Corynebacterium glutamicum*, *Corynebacterium granulomatum*, *Corynebacterium hemolyticum*, *Corynebacterium halophyte*, *Corynebacterium kurstii*. The bacteria include *Corynebacterium jejuni*, *Corynebacterium medroxysum*, *Corynebacterium martensii*, *Corynebacterium microfilii*, *Corynebacterium pustulosa* (Propionibacterium acnes), *Corynebacterium micrometabolicum*, *Corynebacterium propionate*, *Corynebacterium pseudodiphtheriae* (Corynebacterium hoffmannii), *Corynebacterium pseudotuberculosis*, *Corynebacterium sheepii*, *Corynebacterium pyogenes*—*Cryptobacillus pyogenes*, *Corynebacterium urealyticum*, *Corynebacterium nephritis*, *Corynebacterium*, *Corynebacterium striatum*, *Corynebacterium microfilii*, *Corynebacterium ulcerans*, *Corynebacterium urealyticum*, or *Corynebacterium sicca*. This document further provides a method wherein the *Corynebacterium pseudodiphtheriae* strain is selected from the strains listed in Table 1. This document further provides a method wherein *Coccidioidomyces laziensis* is selected from the strains listed in Table 2. This document further provides a method wherein the *Corynebacterium pseudodiphtheriae* strain is selected from the strains listed in Table 1, and wherein *Coccidioidomyces laziensis* is selected from the strains listed in Table 2. This document further provides a pharmaceutical composition comprising mixtures listed in Tables 4 to 7. This document further provides a method wherein the bacterial population is administered intranasally. This article further provides a method in which the live, purified bacterial population is administered orally. This article further provides a method in which the subject is an infant. This article further provides a method in which the subject is a child. This article further provides a method in which the subject is an adult. This article further provides a method in which the live, purified bacterial population is present in a total quantity of up to 10^15 cfu. This article further provides a method in which the live, purified bacterial population is present in a total quantity of 10^3 to 10^12 cfu.
[0059] In some embodiments, this document provides a method for treating COPD, the method comprising: administering to a subject suffering from COPD a live, purified bacterial population, wherein the live, purified bacterial population comprises: a bacterial population of at least one Corynebacterium, optionally at least one Corynebacterium pseudodiphtheriae strain; and optionally at least one Corynebacterium laziness strain. This document further provides a method wherein the Corynebacterium is *Corynebacterium bulgaricum*, *Corynebacterium nonfermentatum*, *Corynebacterium ammoniagenicum*, *Corynebacterium amylopectinum*, *Corynebacterium aureum*, *Corynebacterium aquaticum*, *Corynebacterium otolactum*, *Corynebacterium bovis*, *Corynebacterium diphtheriae*, *Corynebacterium equineumoniae* (now *Rhodococcus equine*), *Corynebacterium viabilityense*, *Corynebacterium flavonoids*, *Corynebacterium glucoside*, *Corynebacterium glutamicum*, *Corynebacterium granulomatum*, *Corynebacterium hemolyticum*, *Corynebacterium halophyte*, *Corynebacterium kurstii*. The bacteria include *Corynebacterium jejuni*, *Corynebacterium medroxysum*, *Corynebacterium martensii*, *Corynebacterium microfilii*, *Corynebacterium pustulosa* (Propionibacterium acnes), *Corynebacterium micrometabolicum*, *Corynebacterium propionate*, *Corynebacterium pseudodiphtheriae* (Corynebacterium hoffmannii), *Corynebacterium pseudotuberculosis*, *Corynebacterium sheepii*, *Corynebacterium pyogenes*—*Cryptobacillus pyogenes*, *Corynebacterium urealyticum*, *Corynebacterium nephritis*, *Corynebacterium*, *Corynebacterium striatum*, *Corynebacterium microfilii*, *Corynebacterium ulcerans*, *Corynebacterium urealyticum*, or *Corynebacterium sicca*. This document further provides a method wherein the *Corynebacterium pseudodiphtheriae* strain is selected from the strains listed in Table 1. This document further provides a method wherein *Coccidioidomyces laziensis* is selected from the strains listed in Table 2. This document further provides a method wherein the *Corynebacterium pseudodiphtheriae* strain is selected from the strains listed in Table 1, and wherein *Coccidioidomyces laziensis* is selected from the strains listed in Table 2. This document further provides a pharmaceutical composition comprising mixtures listed in Tables 4 to 7. This document further provides a method wherein the bacterial population is administered intranasally. This article further provides a method in which the live, purified bacterial population is administered orally. This article further provides a method in which the subject is an infant. This article further provides a method in which the subject is a child. This article further provides a method in which the subject is an adult. This article further provides a method in which the live, purified bacterial population is present in a total quantity of up to 10^15 cfu. This article further provides a method in which the live, purified bacterial population is present in a total quantity of 10^3 to 10^12 cfu.
[0060] In some embodiments, this document provides a method for treating cystic fibrosis, the method comprising: administering to a subject suffering from cystic fibrosis a live, purified bacterial population, wherein the live, purified bacterial population comprises: a bacterial population of at least one Corynebacterium, optionally at least one Corynebacterium pseudodiphtheriae strain; and optionally at least one Corynebacterium laziness strain. This document further provides a method wherein the Corynebacterium is *Corynebacterium bulgaricum*, *Corynebacterium nonfermentatum*, *Corynebacterium ammoniagenicum*, *Corynebacterium amylopectinum*, *Corynebacterium aureum*, *Corynebacterium auriculatum*, *Corynebacterium bovis*, *Corynebacterium diphtheriae*, *Corynebacterium equineumoniae* (now *Rhodococcus equine*), *Corynebacterium effica*, *Corynebacterium flavomarginatis*, *Corynebacterium glutamicum*, *Corynebacterium granulomatum*, *Corynebacterium hemolyticum*, *Corynebacterium halophyte*, *Corynebacterium kurstii*. The bacteria include *Corynebacterium jejuni*, *Corynebacterium medroxysum*, *Corynebacterium martensii*, *Corynebacterium microfilii*, *Corynebacterium pustulosa* (Propionibacterium acnes), *Corynebacterium micrometabolicum*, *Corynebacterium propionate*, *Corynebacterium pseudodiphtheriae* (Corynebacterium hoffmannii), *Corynebacterium pseudotuberculosis*, *Corynebacterium sheepii*, *Corynebacterium pyogenes*—*Cryptobacillus pyogenes*, *Corynebacterium urealyticum*, *Corynebacterium nephritis*, *Corynebacterium*, *Corynebacterium striatum*, *Corynebacterium microfilii*, *Corynebacterium ulcerans*, *Corynebacterium urealyticum*, or *Corynebacterium sicca*. This document further provides a method wherein the *Corynebacterium pseudodiphtheriae* strain is selected from the strains listed in Table 1. This document further provides a method wherein *Coccidioidomyces laziensis* is selected from the strains listed in Table 2. This document further provides a method wherein the *Corynebacterium pseudodiphtheriae* strain is selected from the strains listed in Table 1, and wherein *Coccidioidomyces laziensis* is selected from the strains listed in Table 2. This document further provides a pharmaceutical composition comprising mixtures listed in Tables 4 to 7. This document further provides a method wherein the bacterial population is administered intranasally. This article further provides a method in which the live, purified bacterial population is administered orally. This article further provides a method in which the subject is an infant. This article further provides a method in which the subject is a child. This article further provides a method in which the subject is an adult. This article further provides a method in which the live, purified bacterial population is present in a total quantity of up to 10^15 cfu. This article further provides a method in which the live, purified bacterial population is present in a total quantity of 10^3 to 10^12 cfu.
[0061] In some embodiments, this document provides a kit comprising: a first container comprising a live, purified, and lyophilized bacterial population, the live, purified, and lyophilized bacterial population including multiple strains of *Corynebacterium pseudodiphtheriae*; and a second container comprising a pharmaceutically acceptable excipient. This document further provides a kit wherein the *Corynebacterium pseudodiphtheriae* strain is selected from the strains listed in Table 1. This document further provides a kit wherein the live, purified, and lyophilized bacterial population is present in an amount sufficient to treat respiratory symptoms. This document further provides a kit wherein the live, purified, and lyophilized bacterial population is present in a total amount of up to 10^15 cfu. This document further provides a kit wherein the live, purified, and lyophilized bacterial population is present in a total amount of 10^3 to 10^12 cfu.
[0062] In some embodiments, this document provides a kit comprising: a first container comprising a live, purified, and lyophilized bacterial population, the live, purified, and lyophilized bacterial population comprising a variety of Corynebacterium species; and a second container comprising a pharmaceutically acceptable excipient. This document further provides a kit wherein the Corynebacterium species are selected from the strains listed in Table 1. This document further provides a kit wherein the live, purified, and lyophilized bacterial population is present in an amount sufficient to treat respiratory symptoms. This document further provides a kit wherein the live, purified, and lyophilized bacterial population is present in a total amount of up to 10^15 CFU. This document further provides a kit wherein the live, purified, and lyophilized bacterial population is present in a total amount of 10^3 to 10^12 CFU.
[0063] In some embodiments, this document provides a kit comprising: a first container comprising a live, purified, and lyophilized bacterial population, the live, purified, and lyophilized bacterial population including a variety of *Coccidia laziensis* strains; and a second container comprising a pharmaceutically acceptable excipient. This document further provides a kit wherein the *Coccidia laziensis* strains are selected from those listed in Table 2. This document further provides a kit wherein the live, purified, and lyophilized bacterial population is present in an amount sufficient to treat respiratory symptoms. This document further provides a kit wherein the live, purified, and lyophilized bacterial population is present in a total amount of up to 10^15 cfu. This document further provides a kit wherein the live, purified, and lyophilized bacterial population is present in a total amount of 10^3 to 10^12 cfu.
[0064] In some embodiments, this document provides a kit comprising: a first container comprising a live, purified, and lyophilized bacterial population, the live, purified, and lyophilized bacterial population comprising: multiple strains of *Corynebacterium pseudodiphtheriae*; and multiple strains of *Coccidioidomyces laziensis*; and a second container comprising a pharmaceutically acceptable excipient. This document further provides a kit wherein the *Corynebacterium pseudodiphtheriae* strain is selected from the strains listed in Table 1. This document further provides a kit wherein *Coccidioidomyces laziensis* is selected from the strains listed in Table 2. This document further provides pharmaceutical compositions comprising mixtures listed in Tables 4 to 7. This document further provides a kit wherein the live, purified, and lyophilized bacterial population is present in an amount sufficient to treat respiratory symptoms. This document further provides a kit wherein the live, purified, and lyophilized bacterial population is present in a total amount of up to 10^15 CFU. This document further provides a kit wherein the live, purified, and lyophilized bacterial population is present in a total amount of 10^3 to 10^12 CFU.
[0065] In some embodiments, this document provides a kit comprising: a first container comprising a live, purified, and lyophilized bacterial population present in a total amount of at least 10^3 cfu, the live, purified, and lyophilized bacterial population comprising: *Corynebacterium pseudodiphtheriae* strains; and *Coccidia laziensis* strains; and a second container comprising pharmaceutically acceptable excipients. This document further provides a kit wherein the *Corynebacterium pseudodiphtheriae* strain is selected from the strains listed in Table 1. This document further provides a kit wherein *Coccidia laziensis* is selected from the strains listed in Table 2. This document further provides a kit wherein the live, purified, and lyophilized bacterial population is present in an amount sufficient to treat respiratory symptoms.
[0066] In some embodiments, this document provides a method for treating neurological symptoms, the method comprising administering to a subject suffering from neurological symptoms: a purified, live bacterial population, said purified, live bacterial population comprising at least one bacterial strain present in an amount sufficient to reduce the incidence of pathogen colonization in the nasal cavity, said at least one bacterial strain isolated from the upper respiratory tract of a donor. This document further provides a method wherein said pathogens include Staphylococcus aureus, Streptococcus pneumoniae, Pseudomonas aeruginosa, or Burkholderia pseudomallei. This document further provides a method wherein said pathogens are strains listed in Table 3, including Corynebacterium pseudodiphtheriae; and at least one strain of *Desmodium lazinessum*. This article further provides a method wherein the neurological condition is Parkinson's disease (PD), iLY body syndrome (iLBD), Lewy body dementia (DLB), Alzheimer's disease (AD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP), frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), pure autonomic failure (PAF), schizophrenia, or Creutzfeldt-Jakob disease (CJD). This article further provides a method wherein the subject has olfactory perception impairment. This article further provides a method wherein the live, purified bacterial population is administered intranasally. This article further provides a method wherein the live, purified bacterial population is administered orally. This article further provides a method wherein the subject is an infant. This article further provides a method wherein the subject is a child. This article further provides a method wherein the subject is an adult. This article further provides a method wherein the adult is 65 years of age or older. This article further provides a method wherein the live, purified bacterial population is present in a total amount of up to 10^15 cfu. This paper further provides a method in which the live, purified bacterial population is present in a total amount of 10^3 to 10^12 cfu. This paper further provides a method in which the Corynebacterium species include: crowded Corynebacterium, non-fermenting Corynebacterium, ammonia-producing Corynebacterium, amycotic Corynebacterium, silver Corynebacterium, aquatic Corynebacterium, auricular Corynebacterium, bovine Corynebacterium, diphtheria Corynebacterium, equine Corynebacterium (now *Rhodococcus equi*), effective Corynebacterium, paleo Corynebacterium, glucosinolate Corynebacterium, glutamate Corynebacterium, granulomatous Corynebacterium, hemolytic Corynebacterium, halophyte Corynebacterium, and *Corynebacterium koraiensis*. Corynebacterium jejuni, Corynebacterium medrelli, Corynebacterium martensii, Corynebacterium microfilii, Corynebacterium pustulosa (Propionibacterium pustulosa), Corynebacterium micrometabolicum, Corynebacterium propionate, Corynebacterium pseudodiphtheriae (Corynebacterium hoffmannii), Corynebacterium pseudotuberculosis, Corynebacterium sheepii, Corynebacterium pyogenes—Cryptospirosis, Corynebacterium urealyticum, Corynebacterium nephritis, Corynebacterium, Corynebacterium striatum, Corynebacterium microfilii, Corynebacterium ulcerans, Corynebacterium urealyticum, or Corynebacterium sicca.This document further provides a method wherein the *Corynebacterium pseudodiphtheriae* strain is selected from the strains listed in Table 1. This document further provides a method wherein *Coccidioidomyces laziensis* is selected from the strains listed in Table 2. This document further provides a method wherein the *Corynebacterium pseudodiphtheriae* strain is selected from the strains listed in Table 1, and wherein *Coccidioidomyces laziensis* is selected from the strains listed in Table 2. This document further provides pharmaceutical compositions comprising mixtures listed in Tables 4 to 7.
[0067] In some embodiments, this document provides a method for microbiome modification of a subject, the method comprising administering intranasal administration to a subject in need of: a purified, live bacterial population, the purified, live bacterial population comprising at least one bacterial strain present in an amount sufficient to treat a neurological condition, wherein the at least one bacterial strain is isolated from the upper respiratory tract of a donor. *Corynebacterium pseudodiphtheriae*; and at least one *Coccidioidomyces laziensis* strain. This document further provides a method wherein the neurological condition is Parkinson's disease (PD), iLY body syndrome (iLBD), Lewy body dementia (DLB), Alzheimer's disease (AD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP), frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), pure autonomic failure (PAF), schizophrenia, Creutzfeldt-Jakob disease (CJD), autism spectrum disorder (ASD), post-traumatic stress disorder (PTSD), anxiety disorder, or depression. In some embodiments, ASD is autism, pervasive developmental disorder (PDD-NOS) not otherwise specified, Asperger's syndrome, childhood disintegration disorder (CDD), or Rett syndrome. In some embodiments, anxiety disorder is generalized anxiety disorder, obsessive-compulsive disorder, panic disorder, post-traumatic stress disorder, or social phobia. This document further provides a method wherein the subject has an olfactory perception deficit. This document further provides a method wherein the live, purified bacterial population is administered intranasally. This document further provides a method wherein the live, purified bacterial population is administered orally. This document further provides a method wherein the subject is an infant. This document further provides a method wherein the subject is a child. This document further provides a method wherein the subject is an adult. This document further provides a method wherein the adult is 65 years of age or older. This document further provides a method wherein the live, purified bacterial population is present in a total quantity of up to 10^15 cfu. This document further provides a method wherein the live, purified bacterial population is present in a total quantity of 10^3 to 10^12 cfu.This article further provides a method in which the *Corynebacterium* species include: *Corynebacterium claustrophoides*, *Corynebacterium non-fermenting*, *Corynebacterium ammoniagenic*, *Corynebacterium amylopectinum*, *Corynebacterium auriculatum*, *Corynebacterium bovis*, *Corynebacterium diphtheriae*, *Corynebacterium equineumoniae* (now *Rhodococcus equi*), *Corynebacterium viabilityense*, *Corynebacterium flavonoids*, *Corynebacterium glucoside*, *Corynebacterium glutamicum*, *Corynebacterium granulomatum*, *Corynebacterium hemolyticum*, *Corynebacterium halophyte*, and *Corynebacterium kurstii*. The present invention relates to the following strains of Corynebacterium jejuni, Corynebacterium medricularis, Corynebacterium martensii, Corynebacterium microfiliis, Corynebacterium pustulosa (Propionibacterium acnes), Corynebacterium micrometabolicum, Corynebacterium propionate, Corynebacterium pseudodiphtheriae (Corynebacterium hoffmannii), Corynebacterium pseudotuberculosis, Corynebacterium sheepii, Corynebacterium pyogenes—Cryptospirosis, Corynebacterium urealyticum, Corynebacterium nephrostomyense, Corynebacterium, Corynebacterium striatum, Corynebacterium microfiliis, Corynebacterium ulcerans, Corynebacterium urealyticum, or Corynebacterium sicca. The present invention further provides a method wherein the Corynebacterium pseudodiphtheriae strain is selected from the strains listed in Table 1. The present invention further provides a method wherein *Coccidioidomyces laziensis* is selected from the strains listed in Table 2. The present invention further provides a method wherein the Corynebacterium pseudodiphtheriae strain is selected from the strains listed in Table 1, and wherein *Coccidioidomyces laziensis* is selected from the strains listed in Table 2. The present invention further provides a pharmaceutical composition comprising mixtures listed in Tables 4 to 7.
[0068] In some embodiments, this document provides a method for treating a neurological condition, the method comprising: administering to a subject suffering from a neurological infection a live, purified bacterial population, wherein the live, purified bacterial population comprises: *Corynebacterium pseudodiphtheriae* strains; and *Coccidioidomyces laziensis* strains. *Corynebacterium pseudodiphtheriae*; and at least one *Coccidioidomyces laziensis* strain. This document further provides a method wherein the neurological condition is Parkinson's disease (PD), iLY body syndrome (iLBD), Lewy body dementia (DLB), Alzheimer's disease (AD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP), frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), pure autonomic failure (PAF), schizophrenia, or Creutzfeldt-Jakob disease (CJD). This document further provides a method wherein the subject suffers from olfactory perception impairment. This document further provides a method wherein the live, purified bacterial population is administered intranasally. This document further provides a method wherein the live, purified bacterial population is administered orally. This document further provides a method wherein the subject is an infant. This article further provides a method in which the subject is a child. This article further provides a method in which the subject is an adult. This article further provides a method in which the adult is 65 years of age or older. This article further provides a method in which the live, purified bacterial population is present in a total quantity of up to 10^15 cfu. This article further provides a method in which the live, purified bacterial population is present in a total quantity of 10^3 to 10^12 cfu. This article further provides a method in which the Corynebacterium is crowded Corynebacterium, non-fermenting Corynebacterium, ammonia-producing Corynebacterium, amycotic Corynebacterium, silver Corynebacterium, aquatic Corynebacterium, auricularia Corynebacterium, bovine Corynebacterium, diphtheria Corynebacterium, horse Corynebacterium (now Rhodococcus equi), effective Corynebacterium, paleo Corynebacterium, glucosinolate Corynebacterium, glutamate Corynebacterium, granulomatous Corynebacterium, hemolytic Corynebacterium, halophyte Corynebacterium, Corynebacterium koraiensis. The list includes *Corynebacterium jejuni*, *Corynebacterium medroxyn*, *Corynebacterium martensii*, *Corynebacterium microfilii*, *Corynebacterium pustulosa* (Propionibacterium acnes), *Corynebacterium micrometabolicum*, *Corynebacterium propionate*, *Corynebacterium pseudodiphtheriae* (Corynebacterium hoffmannii), *Corynebacterium pseudotuberculosis*, *Corynebacterium sheepii*, *Corynebacterium pyogenes*—*Cryptobacillus pyogenes*, *Corynebacterium urealyticum*, *Corynebacterium nephritis*, *Corynebacterium*, *Corynebacterium striatum*, *Corynebacterium microfilii*, *Corynebacterium ulcerans*, *Corynebacterium urealyticum*, or *Corynebacterium sicca*. This document further provides a method wherein the *Corynebacterium pseudodiphtheriae* strain is selected from the strains listed in Table 1. This document further provides a method wherein *Coccidioidomyces laziensis* is selected from the strains listed in Table 2. This document further provides a method wherein the *Corynebacterium pseudodiphtheriae* strain is selected from the strains listed in Table 1, and wherein *Coccidioidomyces laziensis* is selected from the strains listed in Table 2.This article further provides pharmaceutical compositions comprising the mixtures listed in Tables 4 to 7.
[0069] In some embodiments, this document provides a method for treating a neurological condition, the method comprising: administering to a subject suffering from a neurological condition a live, purified bacterial population, wherein the live, purified bacterial population comprises a variety of Corynebacterium species, *Corynebacterium pseudodiphtheriae*, and at least one strain of *Coccidia laziensis*. This document further provides a method wherein the neurological condition is Parkinson's disease (PD), iLY body syndrome (iLBD), Lewy body dementia (DLB), Alzheimer's disease (AD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP), frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), pure autonomic failure (PAF), schizophrenia, Creutzfeldt-Jakob disease (CJD), or autism spectrum disorder (ASD). This document further provides a method wherein ASD is autism, pervasive developmental disorder not otherwise specified (PDD-NOS), Asperger's syndrome, childhood disintegration disorder (CDD), or Rett syndrome. This document further provides a method wherein the subject suffers from olfactory perception deficits. This article further provides a method wherein the live, purified bacterial population is administered intranasally. This article further provides a method wherein the live, purified bacterial population is administered orally. This article further provides a method wherein the subject is an infant. This article further provides a method wherein the subject is a child. This article further provides a method wherein the subject is an adult. This article further provides a method wherein the adult is 65 years of age or older. This article further provides a method wherein the live, purified bacterial population is present in a total quantity of up to 10^15 cfu. This article further provides a method wherein the live, purified bacterial population is present in a total quantity of 10^3 to 10^12 cfu. This article further provides a method in which the *Corynebacterium* species include: *Corynebacterium claustrophoides*, *Corynebacterium non-fermenting*, *Corynebacterium ammoniagenic*, *Corynebacterium amylopectinum*, *Corynebacterium auriculatum*, *Corynebacterium bovis*, *Corynebacterium diphtheriae*, *Corynebacterium equineumoniae* (now *Rhodococcus equi*), *Corynebacterium viabilityense*, *Corynebacterium flavonoids*, *Corynebacterium glucoside*, *Corynebacterium glutamicum*, *Corynebacterium granulomatum*, *Corynebacterium hemolyticum*, *Corynebacterium halophyte*, and *Corynebacterium kurstii*. The bacteria include *Corynebacterium jejuni*, *Corynebacterium medroxyn*, *Corynebacterium martensii*, *Corynebacterium microfilii*, *Corynebacterium pustulosa* (Propionibacterium acnes), *Corynebacterium micrometabolicum*, *Corynebacterium propionate*, *Corynebacterium pseudodiphtheriae* (Corynebacterium hoffmannii), *Corynebacterium pseudotuberculosis*, *Corynebacterium sheepii*, *Corynebacterium pyogenes*—*Cryptobacillus pyogenes*, *Corynebacterium urealyticum*, *Corynebacterium nephritis*, *Corynebacterium*, *Corynebacterium striatum*, *Corynebacterium microfilii*, *Corynebacterium ulcerans*, *Corynebacterium urealyticum*, or *Corynebacterium sicca*. This article further provides a method in which the *Corynebacterium pseudodiphtheriae* strain is selected from the strains listed in Table 1. This article further provides a method in which *Corynebacterium lazinessum* is selected from the strains listed in Table 2.This document further provides a method wherein the *Corynebacterium pseudodiphtheriae* strain is selected from the strains listed in Table 1, and wherein *Coccidioidomyces laziensis* is selected from the strains listed in Table 2. This document further provides pharmaceutical compositions comprising mixtures listed in Tables 4 to 7.
[0070] In some embodiments, this document provides a method for treating a neurological condition, the method comprising: administering to a subject suffering from a neurological condition a live, purified bacterial population, wherein the live, purified bacterial population comprises multiple strains of *Corynebacterium laziness*, *Corynebacterium pseudodiphtheriae*, and at least one strain of *Corynebacterium laziness*. This document further provides a method wherein the neurological condition is Parkinson's disease (PD), iLBD, Lewy body dementia (DLB), Alzheimer's disease (AD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP), frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), pure autonomic failure (PAF), schizophrenia, or Creutzfeldt-Jakob disease (CJD). This document further provides a method wherein the subject suffers from olfactory perception impairment. This document further provides a method wherein the live, purified bacterial population is administered intranasally. This document further provides a method wherein the live, purified bacterial population is administered orally. This document further provides a method wherein the subject is an infant. This article further provides a method in which the subject is a child. This article further provides a method in which the subject is an adult. This article further provides a method in which the adult is 65 years of age or older. This article further provides a method in which the live, purified bacterial population is present in a total quantity of up to 10^15 cfu. This article further provides a method in which the live, purified bacterial population is present in a total quantity of 10^3 to 10^12 cfu. This article further provides a method in which the Corynebacterium is crowded Corynebacterium, non-fermenting Corynebacterium, ammonia-producing Corynebacterium, amycotic Corynebacterium, silver Corynebacterium, aquatic Corynebacterium, auricularia Corynebacterium, bovine Corynebacterium, diphtheria Corynebacterium, horse Corynebacterium (now Rhodococcus equi), effective Corynebacterium, paleo Corynebacterium, glucosinolate Corynebacterium, glutamate Corynebacterium, granulomatous Corynebacterium, hemolytic Corynebacterium, halophyte Corynebacterium, Corynebacterium koraiensis. The present invention relates to the following strains of Corynebacterium jejuni, Corynebacterium medricularis, Corynebacterium martensii, Corynebacterium microfiliis, Corynebacterium pustulosa (Propionibacterium acnes), Corynebacterium micrometabolicum, Corynebacterium propionate, Corynebacterium pseudodiphtheriae (Corynebacterium hoffmannii), Corynebacterium pseudotuberculosis, Corynebacterium sheepii, Corynebacterium pyogenes—Cryptospirosis, Corynebacterium urealyticum, Corynebacterium nephrostomyense, Corynebacterium, Corynebacterium striatum, Corynebacterium microfiliis, Corynebacterium ulcerans, Corynebacterium urealyticum, or Corynebacterium sicca. The present invention further provides a method wherein the Corynebacterium pseudodiphtheriae strain is selected from the strains listed in Table 1. The present invention further provides a method wherein *Coccidioidomyces laziensis* is selected from the strains listed in Table 2. The present invention further provides a method wherein the Corynebacterium pseudodiphtheriae strain is selected from the strains listed in Table 1, and wherein *Coccidioidomyces laziensis* is selected from the strains listed in Table 2. The present invention further provides a pharmaceutical composition comprising mixtures listed in Tables 4 to 7.
[0071] In some embodiments, this document provides a method for treating a neurological condition, the method comprising administering to a subject suffering from a neurological condition a live, purified bacterial population, wherein the live, purified bacterial population comprises: multiple strains of Corynebacterium pseudodiphtheriae; and at least one strain of Coccidia laziensis. This document further provides a method wherein the neurological condition is Parkinson's disease (PD), iLY body syndrome (iLBD), Lewy body dementia (DLB), Alzheimer's disease (AD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP), frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), pure autonomic failure (PAF), schizophrenia, Creutzfeldt-Jakob disease (CJD), autism spectrum disorder (ASD) or post-traumatic stress disorder (PTSD), anxiety disorder, or depression. In some embodiments, ASD is autism, pervasive developmental disorder not otherwise specified (PDD-NOS), Asperger's syndrome, childhood disintegration disorder (CDD), or Rett syndrome. In some embodiments, the anxiety disorder is generalized anxiety disorder, obsessive-compulsive disorder, panic disorder, post-traumatic stress disorder, or social phobia. This document further provides a method wherein the subject has an olfactory perception deficit. This document further provides a method wherein the live, purified bacterial population is administered intranasally. This document further provides a method wherein the live, purified bacterial population is administered orally. This document further provides a method wherein the subject is an infant. This document further provides a method wherein the subject is a child. This document further provides a method wherein the subject is an adult. This document further provides a method wherein the adult is 65 years of age or older. This document further provides a method wherein the live, purified bacterial population is present in a total quantity of up to 10^15 cfu. This document further provides a method wherein the live, purified bacterial population is present in a total quantity of 10^3 to 10^12 cfu. This article further provides a method in which the *Corynebacterium* species include: *Corynebacterium claustrophoides*, *Corynebacterium non-fermenting*, *Corynebacterium ammoniagenic*, *Corynebacterium amylopectinum*, *Corynebacterium auriculatum*, *Corynebacterium bovis*, *Corynebacterium diphtheriae*, *Corynebacterium equineumoniae* (now *Rhodococcus equi*), *Corynebacterium viabilityense*, *Corynebacterium flavonoids*, *Corynebacterium glucoside*, *Corynebacterium glutamicum*, *Corynebacterium granulomatum*, *Corynebacterium hemolyticum*, *Corynebacterium halophyte*, and *Corynebacterium kurstii*. Corynebacterium jejuni, Corynebacterium medrelli, Corynebacterium martensii, Corynebacterium microfilii, Corynebacterium pustulosa (Propionibacterium pustulosa), Corynebacterium micrometabolicum, Corynebacterium propionate, Corynebacterium pseudodiphtheriae (Corynebacterium hoffmannii), Corynebacterium pseudotuberculosis, Corynebacterium sheepii, Corynebacterium pyogenes—Cryptospirosis, Corynebacterium urealyticum, Corynebacterium nephritis, Corynebacterium, Corynebacterium striatum, Corynebacterium microfilii, Corynebacterium ulcerans, Corynebacterium urealyticum, or Corynebacterium sicca.This document further provides a method wherein the *Corynebacterium pseudodiphtheriae* strain is selected from the strains listed in Table 1. This document further provides a method wherein *Coccidioidomyces laziensis* is selected from the strains listed in Table 2. This document further provides a method wherein the *Corynebacterium pseudodiphtheriae* strain is selected from the strains listed in Table 1, and wherein *Coccidioidomyces laziensis* is selected from the strains listed in Table 2. This document further provides pharmaceutical compositions comprising mixtures listed in Tables 4 to 7.
[0072] In some embodiments, this document provides a method for treating Parkinson's disease, the method comprising: administering to a subject suffering from Parkinson's disease a live, purified bacterial population, wherein the live, purified bacterial population comprises: a bacterial population of at least one Corynebacterium, optionally at least one Corynebacterium pseudodiphtheriae strain; and optionally at least one Coccidia laziensis strain. This document further provides a method wherein the live, purified bacterial population is administered intranasally. This document further provides a method wherein the live, purified bacterial population is administered orally. This document further provides a method wherein the subject is an infant. This document further provides a method wherein the subject is a child. This document further provides a method wherein the subject is an adult. This document further provides a method wherein the adult is 65 years of age or older. This document further provides a method wherein the live, purified bacterial population is present in a total quantity of up to 10^15 cfu. This document further provides a method wherein the live, purified bacterial population is present in a total quantity of 10^3 cfu to 10^12 cfu. This article further provides a method in which the *Corynebacterium* species include: *Corynebacterium claustrophoides*, *Corynebacterium non-fermenting*, *Corynebacterium ammoniagenic*, *Corynebacterium amylopectinum*, *Corynebacterium auriculatum*, *Corynebacterium bovis*, *Corynebacterium diphtheriae*, *Corynebacterium equineumoniae* (now *Rhodococcus equi*), *Corynebacterium viabilityense*, *Corynebacterium flavonoids*, *Corynebacterium glucoside*, *Corynebacterium glutamicum*, *Corynebacterium granulomatum*, *Corynebacterium hemolyticum*, *Corynebacterium halophyte*, and *Corynebacterium kurstii*. The present invention relates to the following strains of Corynebacterium jejuni, Corynebacterium medricularis, Corynebacterium martensii, Corynebacterium microfiliis, Corynebacterium pustulosa (Propionibacterium acnes), Corynebacterium micrometabolicum, Corynebacterium propionate, Corynebacterium pseudodiphtheriae (Corynebacterium hoffmannii), Corynebacterium pseudotuberculosis, Corynebacterium sheepii, Corynebacterium pyogenes—Cryptospirosis, Corynebacterium urealyticum, Corynebacterium nephrostomyense, Corynebacterium, Corynebacterium striatum, Corynebacterium microfiliis, Corynebacterium ulcerans, Corynebacterium urealyticum, or Corynebacterium sicca. The present invention further provides a method wherein the Corynebacterium pseudodiphtheriae strain is selected from the strains listed in Table 1. The present invention further provides a method wherein *Coccidioidomyces laziensis* is selected from the strains listed in Table 2. The present invention further provides a method wherein the Corynebacterium pseudodiphtheriae strain is selected from the strains listed in Table 1, and wherein *Coccidioidomyces laziensis* is selected from the strains listed in Table 2. The present invention further provides a pharmaceutical composition comprising mixtures listed in Tables 4 to 7.
[0073] In some embodiments, this document provides a method for treating occasional Lewy body syndrome, the method comprising: administering to a subject suffering from occasional Lewy body syndrome a live, purified bacterial population, wherein the live, purified bacterial population comprises: a bacterial population of at least one Corynebacterium, optionally at least one Corynebacterium pseudodiphtheriae strain; and optionally at least one Coccidia laziensis strain. This document further provides a method wherein the live, purified bacterial population is administered intranasally. This document further provides a method wherein the live, purified bacterial population is administered orally. This document further provides a method wherein the subject is an infant. This document further provides a method wherein the subject is a child. This document further provides a method wherein the subject is an adult. This document further provides a method wherein the adult is 65 years of age or older. This document further provides a method wherein the live, purified bacterial population is present in a total quantity of up to 10^15 cfu. This document further provides a method wherein the live, purified bacterial population is present in a total quantity of 10^3 cfu to 10^12 cfu. This article further provides a method in which the *Corynebacterium* species include: *Corynebacterium claustrophoides*, *Corynebacterium non-fermenting*, *Corynebacterium ammoniagenic*, *Corynebacterium amylopectinum*, *Corynebacterium auriculatum*, *Corynebacterium bovis*, *Corynebacterium diphtheriae*, *Corynebacterium equineumoniae* (now *Rhodococcus equi*), *Corynebacterium viabilityense*, *Corynebacterium flavonoids*, *Corynebacterium glucoside*, *Corynebacterium glutamicum*, *Corynebacterium granulomatum*, *Corynebacterium hemolyticum*, *Corynebacterium halophyte*, and *Corynebacterium kurstii*. The present invention relates to the following strains of Corynebacterium jejuni, Corynebacterium medricularis, Corynebacterium martensii, Corynebacterium microfiliis, Corynebacterium pustulosa (Propionibacterium acnes), Corynebacterium micrometabolicum, Corynebacterium propionate, Corynebacterium pseudodiphtheriae (Corynebacterium hoffmannii), Corynebacterium pseudotuberculosis, Corynebacterium sheepii, Corynebacterium pyogenes—Cryptospirosis, Corynebacterium urealyticum, Corynebacterium nephrostomyense, Corynebacterium, Corynebacterium striatum, Corynebacterium microfiliis, Corynebacterium ulcerans, Corynebacterium urealyticum, or Corynebacterium sicca. The present invention further provides a method wherein the Corynebacterium pseudodiphtheriae strain is selected from the strains listed in Table 1. The present invention further provides a method wherein *Coccidioidomyces laziensis* is selected from the strains listed in Table 2. The present invention further provides a method wherein the Corynebacterium pseudodiphtheriae strain is selected from the strains listed in Table 1, and wherein *Coccidioidomyces laziensis* is selected from the strains listed in Table 2. The present invention further provides a pharmaceutical composition comprising mixtures listed in Tables 4 to 7.
[0074] In some embodiments, this document provides a method for treating Lewy body dementia, the method comprising: administering to a subject suffering from Lewy body dementia a live, purified bacterial population, wherein the live, purified bacterial population comprises: a bacterial population of at least one Corynebacterium, optionally at least one Corynebacterium pseudodiphtheriae strain; and optionally at least one Coccidia laziensis strain. This document further provides a method wherein the live, purified bacterial population is administered intranasally. This document further provides a method wherein the live, purified bacterial population is administered orally. This document further provides a method wherein the subject is an infant. This document further provides a method wherein the subject is a child. This document further provides a method wherein the subject is an adult. This document further provides a method wherein the adult is 65 years of age or older. This document further provides a method wherein the live, purified bacterial population is present in a total quantity of up to 10^15 cfu. This document further provides a method wherein the live, purified bacterial population is present in a total quantity of 10^3 cfu to 10^12 cfu. This article further provides a method in which the *Corynebacterium* species include: *Corynebacterium claustrophoides*, *Corynebacterium non-fermenting*, *Corynebacterium ammoniagenic*, *Corynebacterium amylopectinum*, *Corynebacterium auriculatum*, *Corynebacterium bovis*, *Corynebacterium diphtheriae*, *Corynebacterium equineumoniae* (now *Rhodococcus equi*), *Corynebacterium viabilityense*, *Corynebacterium flavonoids*, *Corynebacterium glucoside*, *Corynebacterium glutamicum*, *Corynebacterium granulomatum*, *Corynebacterium hemolyticum*, *Corynebacterium halophyte*, and *Corynebacterium kurstii*. The present invention relates to the following strains of Corynebacterium jejuni, Corynebacterium medricularis, Corynebacterium martensii, Corynebacterium microfiliis, Corynebacterium pustulosa (Propionibacterium acnes), Corynebacterium micrometabolicum, Corynebacterium propionate, Corynebacterium pseudodiphtheriae (Corynebacterium hoffmannii), Corynebacterium pseudotuberculosis, Corynebacterium sheepii, Corynebacterium pyogenes—Cryptospirosis, Corynebacterium urealyticum, Corynebacterium nephrostomyense, Corynebacterium, Corynebacterium striatum, Corynebacterium microfiliis, Corynebacterium ulcerans, Corynebacterium urealyticum, or Corynebacterium sicca. The present invention further provides a method wherein the Corynebacterium pseudodiphtheriae strain is selected from the strains listed in Table 1. The present invention further provides a method wherein *Coccidioidomyces laziensis* is selected from the strains listed in Table 2. The present invention further provides a method wherein the Corynebacterium pseudodiphtheriae strain is selected from the strains listed in Table 1, and wherein *Coccidioidomyces laziensis* is selected from the strains listed in Table 2. The present invention further provides a pharmaceutical composition comprising mixtures listed in Tables 4 to 7.
[0075] In some embodiments, this document provides a method for treating Alzheimer's disease, the method comprising: administering to a subject suffering from Alzheimer's disease a live, purified bacterial population, wherein the live, purified bacterial population comprises: a bacterial population of at least one Corynebacterium, optionally at least one Corynebacterium pseudodiphtheriae strain; and optionally at least one Coccidia laziensis strain. This document further provides a method wherein the live, purified bacterial population is administered intranasally. This document further provides a method wherein the live, purified bacterial population is administered orally. This document further provides a method wherein the subject is an infant. This document further provides a method wherein the subject is a child. This document further provides a method wherein the subject is an adult. This document further provides a method wherein the adult is 65 years of age or older. This document further provides a method wherein the live, purified bacterial population is present in a total quantity of up to 10^15 cfu. This document further provides a method wherein the live, purified bacterial population is present in a total quantity of 10^3 cfu to 10^12 cfu. This article further provides a method in which the *Corynebacterium* species include: *Corynebacterium claustrophoides*, *Corynebacterium non-fermenting*, *Corynebacterium ammoniagenic*, *Corynebacterium amylopectinum*, *Corynebacterium auriculatum*, *Corynebacterium bovis*, *Corynebacterium diphtheriae*, *Corynebacterium equineumoniae* (now *Rhodococcus equi*), *Corynebacterium viabilityense*, *Corynebacterium flavonoids*, *Corynebacterium glucoside*, *Corynebacterium glutamicum*, *Corynebacterium granulomatum*, *Corynebacterium hemolyticum*, *Corynebacterium halophyte*, and *Corynebacterium kurstii*. The present invention relates to the following strains of Corynebacterium jejuni, Corynebacterium medricularis, Corynebacterium martensii, Corynebacterium microfiliis, Corynebacterium pustulosa (Propionibacterium acnes), Corynebacterium micrometabolicum, Corynebacterium propionate, Corynebacterium pseudodiphtheriae (Corynebacterium hoffmannii), Corynebacterium pseudotuberculosis, Corynebacterium sheepii, Corynebacterium pyogenes—Cryptospirosis, Corynebacterium urealyticum, Corynebacterium nephrostomyense, Corynebacterium, Corynebacterium striatum, Corynebacterium microfiliis, Corynebacterium ulcerans, Corynebacterium urealyticum, or Corynebacterium sicca. The present invention further provides a method wherein the Corynebacterium pseudodiphtheriae strain is selected from the strains listed in Table 1. The present invention further provides a method wherein *Coccidioidomyces laziensis* is selected from the strains listed in Table 2. The present invention further provides a method wherein the Corynebacterium pseudodiphtheriae strain is selected from the strains listed in Table 1, and wherein *Coccidioidomyces laziensis* is selected from the strains listed in Table 2. The present invention further provides a pharmaceutical composition comprising mixtures listed in Tables 4 to 7.
[0076] In some embodiments, this document provides a method for treating multiple system atrophy, the method comprising: administering to a subject suffering from multiple system atrophy a live, purified bacterial population, wherein the live, purified bacterial population comprises: a bacterial population of at least one Corynebacterium, optionally at least one Corynebacterium pseudodiphtheriae strain; and optionally at least one Coccus laziensis strain. This document further provides a method wherein the live, purified bacterial population is administered intranasally. This document further provides a method wherein the live, purified bacterial population is administered orally. This document further provides a method wherein the subject is an infant. This document further provides a method wherein the subject is a child. This document further provides a method wherein the subject is an adult. This document further provides a method wherein the adult is 65 years of age or older. This document further provides a method wherein the live, purified bacterial population is present in a total quantity of up to 10^15 cfu. This document further provides a method wherein the live, purified bacterial population is present in a total quantity of 10^3 cfu to 10^12 cfu. This article further provides a method in which the *Corynebacterium* species include: *Corynebacterium claustrophoides*, *Corynebacterium non-fermenting*, *Corynebacterium ammoniagenic*, *Corynebacterium amylopectinum*, *Corynebacterium auriculatum*, *Corynebacterium bovis*, *Corynebacterium diphtheriae*, *Corynebacterium equineumoniae* (now *Rhodococcus equi*), *Corynebacterium viabilityense*, *Corynebacterium flavonoids*, *Corynebacterium glucoside*, *Corynebacterium glutamicum*, *Corynebacterium granulomatum*, *Corynebacterium hemolyticum*, *Corynebacterium halophyte*, and *Corynebacterium kurstii*. The present invention relates to the following strains of Corynebacterium jejuni, Corynebacterium medricularis, Corynebacterium martensii, Corynebacterium microfiliis, Corynebacterium pustulosa (Propionibacterium acnes), Corynebacterium micrometabolicum, Corynebacterium propionate, Corynebacterium pseudodiphtheriae (Corynebacterium hoffmannii), Corynebacterium pseudotuberculosis, Corynebacterium sheepii, Corynebacterium pyogenes—Cryptospirosis, Corynebacterium urealyticum, Corynebacterium nephrostomyense, Corynebacterium, Corynebacterium striatum, Corynebacterium microfiliis, Corynebacterium ulcerans, Corynebacterium urealyticum, or Corynebacterium sicca. The present invention further provides a method wherein the Corynebacterium pseudodiphtheriae strain is selected from the strains listed in Table 1. The present invention further provides a method wherein *Coccidioidomyces laziensis* is selected from the strains listed in Table 2. The present invention further provides a method wherein the Corynebacterium pseudodiphtheriae strain is selected from the strains listed in Table 1, and wherein *Coccidioidomyces laziensis* is selected from the strains listed in Table 2. The present invention further provides a pharmaceutical composition comprising mixtures listed in Tables 4 to 7.
[0077] In some embodiments, this document provides a method for treating progressive supranuclear palsy, the method comprising: administering to a subject suffering from progressive supranuclear palsy a live, purified bacterial population, wherein the live, purified bacterial population comprises: a bacterial population of at least one Corynebacterium, optionally at least one Corynebacterium pseudodiphtheriae strain; and optionally at least one Coccidia laziensis strain. This document further provides a method wherein the live, purified bacterial population is administered intranasally. This document further provides a method wherein the live, purified bacterial population is administered orally. This document further provides a method wherein the subject is an infant. This document further provides a method wherein the subject is a child. This document further provides a method wherein the subject is an adult. This document further provides a method wherein the adult is 65 years of age or older. This document further provides a method wherein the live, purified bacterial population is present in a total quantity of up to 10^15 cfu. This document further provides a method wherein the live, purified bacterial population is present in a total quantity of 10^3 cfu to 10^12 cfu. This article further provides a method in which the *Corynebacterium* species include: *Corynebacterium claustrophoides*, *Corynebacterium non-fermenting*, *Corynebacterium ammoniagenic*, *Corynebacterium amylopectinum*, *Corynebacterium auriculatum*, *Corynebacterium bovis*, *Corynebacterium diphtheriae*, *Corynebacterium equineumoniae* (now *Rhodococcus equi*), *Corynebacterium viabilityense*, *Corynebacterium flavonoids*, *Corynebacterium glucoside*, *Corynebacterium glutamicum*, *Corynebacterium granulomatum*, *Corynebacterium hemolyticum*, *Corynebacterium halophyte*, and *Corynebacterium kurstii*. The present invention relates to the following strains of Corynebacterium jejuni, Corynebacterium medricularis, Corynebacterium martensii, Corynebacterium microfiliis, Corynebacterium pustulosa (Propionibacterium acnes), Corynebacterium micrometabolicum, Corynebacterium propionate, Corynebacterium pseudodiphtheriae (Corynebacterium hoffmannii), Corynebacterium pseudotuberculosis, Corynebacterium sheepii, Corynebacterium pyogenes—Cryptospirosis, Corynebacterium urealyticum, Corynebacterium nephrostomyense, Corynebacterium, Corynebacterium striatum, Corynebacterium microfiliis, Corynebacterium ulcerans, Corynebacterium urealyticum, or Corynebacterium sicca. The present invention further provides a method wherein the Corynebacterium pseudodiphtheriae strain is selected from the strains listed in Table 1. The present invention further provides a method wherein *Coccidioidomyces laziensis* is selected from the strains listed in Table 2. The present invention further provides a method wherein the Corynebacterium pseudodiphtheriae strain is selected from the strains listed in Table 1, and wherein *Coccidioidomyces laziensis* is selected from the strains listed in Table 2. The present invention further provides a pharmaceutical composition comprising mixtures listed in Tables 4 to 7.
[0078] In some embodiments, this document provides a method for treating frontotemporal dementia, the method comprising: administering to a subject suffering from frontotemporal dementia a live, purified bacterial population, wherein the live, purified bacterial population comprises: a bacterial population of at least one Corynebacterium, optionally at least one Corynebacterium pseudodiphtheriae strain; and optionally at least one Coccidia laziensis strain. This document further provides a method wherein the live, purified bacterial population is administered intranasally. This document further provides a method wherein the live, purified bacterial population is administered orally. This document further provides a method wherein the subject is an infant. This document further provides a method wherein the subject is a child. This document further provides a method wherein the subject is an adult. This document further provides a method wherein the adult is 65 years of age or older. This document further provides a method wherein the live, purified bacterial population is present in a total quantity of up to 10^15 cfu. This document further provides a method wherein the live, purified bacterial population is present in a total quantity of 10^3 cfu to 10^12 cfu. This article further provides a method in which the *Corynebacterium* species include: *Corynebacterium claustrophoides*, *Corynebacterium non-fermenting*, *Corynebacterium ammoniagenic*, *Corynebacterium amylopectinum*, *Corynebacterium auriculatum*, *Corynebacterium bovis*, *Corynebacterium diphtheriae*, *Corynebacterium equineumoniae* (now *Rhodococcus equi*), *Corynebacterium viabilityense*, *Corynebacterium flavonoids*, *Corynebacterium glucoside*, *Corynebacterium glutamicum*, *Corynebacterium granulomatum*, *Corynebacterium hemolyticum*, *Corynebacterium halophyte*, and *Corynebacterium kurstii*. The present invention relates to the following strains of Corynebacterium jejuni, Corynebacterium medricularis, Corynebacterium martensii, Corynebacterium microfiliis, Corynebacterium pustulosa (Propionibacterium acnes), Corynebacterium micrometabolicum, Corynebacterium propionate, Corynebacterium pseudodiphtheriae (Corynebacterium hoffmannii), Corynebacterium pseudotuberculosis, Corynebacterium sheepii, Corynebacterium pyogenes—Cryptospirosis, Corynebacterium urealyticum, Corynebacterium nephrostomyense, Corynebacterium, Corynebacterium striatum, Corynebacterium microfiliis, Corynebacterium ulcerans, Corynebacterium urealyticum, or Corynebacterium sicca. The present invention further provides a method wherein the Corynebacterium pseudodiphtheriae strain is selected from the strains listed in Table 1. The present invention further provides a method wherein *Coccidioidomyces laziensis* is selected from the strains listed in Table 2. The present invention further provides a method wherein the Corynebacterium pseudodiphtheriae strain is selected from the strains listed in Table 1, and wherein *Coccidioidomyces laziensis* is selected from the strains listed in Table 2. The present invention further provides a pharmaceutical composition comprising mixtures listed in Tables 4 to 7.
[0079] In some embodiments, this document provides a method for treating amyotrophic lateral sclerosis (ALS), the method comprising: administering to a subject suffering from ALS a live, purified bacterial population, wherein the live, purified bacterial population comprises: a bacterial population of at least one Corynebacterium, optionally at least one Corynebacterium pseudodiphtheriae strain; and optionally at least one Coccus laziensis strain. This document further provides a method wherein the live, purified bacterial population is administered intranasally. This document further provides a method wherein the live, purified bacterial population is administered orally. This document further provides a method wherein the subject is an infant. This document further provides a method wherein the subject is a child. This document further provides a method wherein the subject is an adult. This document further provides a method wherein the adult is 65 years of age or older. This document further provides a method wherein the live, purified bacterial population is present in a total quantity of up to 10^15 cfu. This document further provides a method wherein the live, purified bacterial population is present in a total quantity of 10^3 cfu to 10^12 cfu. This article further provides a method in which the *Corynebacterium* species include: *Corynebacterium claustrophoides*, *Corynebacterium non-fermenting*, *Corynebacterium ammoniagenic*, *Corynebacterium amylopectinum*, *Corynebacterium auriculatum*, *Corynebacterium bovis*, *Corynebacterium diphtheriae*, *Corynebacterium equineumoniae* (now *Rhodococcus equi*), *Corynebacterium viabilityense*, *Corynebacterium flavonoids*, *Corynebacterium glucoside*, *Corynebacterium glutamicum*, *Corynebacterium granulomatum*, *Corynebacterium hemolyticum*, *Corynebacterium halophyte*, and *Corynebacterium kurstii*. The present invention relates to the following strains of Corynebacterium jejuni, Corynebacterium medricularis, Corynebacterium martensii, Corynebacterium microfiliis, Corynebacterium pustulosa (Propionibacterium acnes), Corynebacterium micrometabolicum, Corynebacterium propionate, Corynebacterium pseudodiphtheriae (Corynebacterium hoffmannii), Corynebacterium pseudotuberculosis, Corynebacterium sheepii, Corynebacterium pyogenes—Cryptospirosis, Corynebacterium urealyticum, Corynebacterium nephrostomyense, Corynebacterium, Corynebacterium striatum, Corynebacterium microfiliis, Corynebacterium ulcerans, Corynebacterium urealyticum, or Corynebacterium sicca. The present invention further provides a method wherein the Corynebacterium pseudodiphtheriae strain is selected from the strains listed in Table 1. The present invention further provides a method wherein *Coccidioidomyces laziensis* is selected from the strains listed in Table 2. The present invention further provides a method wherein the Corynebacterium pseudodiphtheriae strain is selected from the strains listed in Table 1, and wherein *Coccidioidomyces laziensis* is selected from the strains listed in Table 2. The present invention further provides a pharmaceutical composition comprising mixtures listed in Tables 4 to 7.
[0080] In some embodiments, this document provides a method for treating pure autonomic nervous system failure, the method comprising: administering to a subject suffering from pure autonomic nervous system failure a live, purified bacterial population, wherein the live, purified bacterial population comprises: at least one Corynebacterium, optionally at least one Corynebacterium pseudodiphtheriae strain; and optionally at least one Coccidia laziensis strain. This document further provides a method wherein the live, purified bacterial population is administered intranasally. This document further provides a method wherein the live, purified bacterial population is administered orally. This document further provides a method wherein the subject is an infant. This document further provides a method wherein the subject is a child. This document further provides a method wherein the subject is an adult. This document further provides a method wherein the adult is 65 years of age or older. This document further provides a method wherein the live, purified bacterial population is present in a total quantity of up to 10^15 cfu. This document further provides a method wherein the live, purified bacterial population is present in a total quantity of 10^3 cfu to 10^12 cfu. This article further provides a method in which the *Corynebacterium* species include: *Corynebacterium claustrophoides*, *Corynebacterium non-fermenting*, *Corynebacterium ammoniagenic*, *Corynebacterium amylopectinum*, *Corynebacterium auriculatum*, *Corynebacterium bovis*, *Corynebacterium diphtheriae*, *Corynebacterium equineumoniae* (now *Rhodococcus equi*), *Corynebacterium viabilityense*, *Corynebacterium flavonoids*, *Corynebacterium glucoside*, *Corynebacterium glutamicum*, *Corynebacterium granulomatum*, *Corynebacterium hemolyticum*, *Corynebacterium halophyte*, and *Corynebacterium kurstii*. The present invention relates to the following strains of Corynebacterium jejuni, Corynebacterium medricularis, Corynebacterium martensii, Corynebacterium microfiliis, Corynebacterium pustulosa (Propionibacterium acnes), Corynebacterium micrometabolicum, Corynebacterium propionate, Corynebacterium pseudodiphtheriae (Corynebacterium hoffmannii), Corynebacterium pseudotuberculosis, Corynebacterium sheepii, Corynebacterium pyogenes—Cryptospirosis, Corynebacterium urealyticum, Corynebacterium nephrostomyense, Corynebacterium, Corynebacterium striatum, Corynebacterium microfiliis, Corynebacterium ulcerans, Corynebacterium urealyticum, or Corynebacterium sicca. The present invention further provides a method wherein the Corynebacterium pseudodiphtheriae strain is selected from the strains listed in Table 1. The present invention further provides a method wherein *Coccidioidomyces laziensis* is selected from the strains listed in Table 2. The present invention further provides a method wherein the Corynebacterium pseudodiphtheriae strain is selected from the strains listed in Table 1, and wherein *Coccidioidomyces laziensis* is selected from the strains listed in Table 2. The present invention further provides a pharmaceutical composition comprising mixtures listed in Tables 4 to 7.
[0081] In some embodiments, this document provides a method for treating schizophrenia, the method comprising: administering to a subject suffering from schizophrenia a live, purified bacterial population, wherein the live, purified bacterial population comprises: a bacterial population of at least one Corynebacterium, optionally at least one Corynebacterium pseudodiphtheriae strain; and optionally at least one Coccidia laziensis strain. This document further provides a method wherein the live, purified bacterial population is administered intranasally. This document further provides a method wherein the live, purified bacterial population is administered orally. This document further provides a method wherein the subject is an infant. This document further provides a method wherein the subject is a child. This document further provides a method wherein the subject is an adult. This document further provides a method wherein the adult is 65 years of age or older. This document further provides a method wherein the live, purified bacterial population is present in a total quantity of up to 10^15 cfu. This document further provides a method wherein the live, purified bacterial population is present in a total quantity of 10^3 cfu to 10^12 cfu. This article further provides a method in which the *Corynebacterium* species include: *Corynebacterium claustrophoides*, *Corynebacterium non-fermenting*, *Corynebacterium ammoniagenic*, *Corynebacterium amylopectinum*, *Corynebacterium auriculatum*, *Corynebacterium bovis*, *Corynebacterium diphtheriae*, *Corynebacterium equineumoniae* (now *Rhodococcus equi*), *Corynebacterium viabilityense*, *Corynebacterium flavonoids*, *Corynebacterium glucoside*, *Corynebacterium glutamicum*, *Corynebacterium granulomatum*, *Corynebacterium hemolyticum*, *Corynebacterium halophyte*, and *Corynebacterium kurstii*. The present invention relates to the following strains of Corynebacterium jejuni, Corynebacterium medricularis, Corynebacterium martensii, Corynebacterium microfiliis, Corynebacterium pustulosa (Propionibacterium acnes), Corynebacterium micrometabolicum, Corynebacterium propionate, Corynebacterium pseudodiphtheriae (Corynebacterium hoffmannii), Corynebacterium pseudotuberculosis, Corynebacterium sheepii, Corynebacterium pyogenes—Cryptospirosis, Corynebacterium urealyticum, Corynebacterium nephrostomyense, Corynebacterium, Corynebacterium striatum, Corynebacterium microfiliis, Corynebacterium ulcerans, Corynebacterium urealyticum, or Corynebacterium sicca. The present invention further provides a method wherein the Corynebacterium pseudodiphtheriae strain is selected from the strains listed in Table 1. The present invention further provides a method wherein *Coccidioidomyces laziensis* is selected from the strains listed in Table 2. The present invention further provides a method wherein the Corynebacterium pseudodiphtheriae strain is selected from the strains listed in Table 1, and wherein *Coccidioidomyces laziensis* is selected from the strains listed in Table 2. The present invention further provides a pharmaceutical composition comprising mixtures listed in Tables 4 to 7.
[0082] In some embodiments, this document provides a method for treating Creutzfeldt-Jakobacter pylori (CJD), the method comprising: administering to a subject suffering from CJD a live, purified bacterial population, wherein the live, purified bacterial population comprises: a bacterial population of at least one Corynebacterium, optionally at least one Corynebacterium pseudodiphtheriae strain; and optionally at least one Coccus laziensis strain. This document further provides a method wherein the live, purified bacterial population is administered intranasally. This document further provides a method wherein the live, purified bacterial population is administered orally. This document further provides a method wherein the subject is an infant. This document further provides a method wherein the subject is a child. This document further provides a method wherein the subject is an adult. This document further provides a method wherein the adult is 65 years of age or older. This document further provides a method wherein the live, purified bacterial population is present in a total quantity of up to 10^15 cfu. This document further provides a method wherein the live, purified bacterial population is present in a total quantity of 10^3 cfu to 10^12 cfu. This article further provides a method in which the *Corynebacterium* species include: *Corynebacterium claustrophoides*, *Corynebacterium non-fermenting*, *Corynebacterium ammoniagenic*, *Corynebacterium amylopectinum*, *Corynebacterium auriculatum*, *Corynebacterium bovis*, *Corynebacterium diphtheriae*, *Corynebacterium equineumoniae* (now *Rhodococcus equi*), *Corynebacterium viabilityense*, *Corynebacterium flavonoids*, *Corynebacterium glucoside*, *Corynebacterium glutamicum*, *Corynebacterium granulomatum*, *Corynebacterium hemolyticum*, *Corynebacterium halophyte*, and *Corynebacterium kurstii*. The present invention relates to the following strains of Corynebacterium jejuni, Corynebacterium medricularis, Corynebacterium martensii, Corynebacterium microfiliis, Corynebacterium pustulosa (Propionibacterium acnes), Corynebacterium micrometabolicum, Corynebacterium propionate, Corynebacterium pseudodiphtheriae (Corynebacterium hoffmannii), Corynebacterium pseudotuberculosis, Corynebacterium sheepii, Corynebacterium pyogenes—Cryptospirosis, Corynebacterium urealyticum, Corynebacterium nephrostomyense, Corynebacterium, Corynebacterium striatum, Corynebacterium microfiliis, Corynebacterium ulcerans, Corynebacterium urealyticum, or Corynebacterium sicca. The present invention further provides a method wherein the Corynebacterium pseudodiphtheriae strain is selected from the strains listed in Table 1. The present invention further provides a method wherein *Coccidioidomyces laziensis* is selected from the strains listed in Table 2. The present invention further provides a method wherein the Corynebacterium pseudodiphtheriae strain is selected from the strains listed in Table 1, and wherein *Coccidioidomyces laziensis* is selected from the strains listed in Table 2. The present invention further provides a pharmaceutical composition comprising mixtures listed in Tables 4 to 7.
[0083] In some embodiments, this document provides a method for treating autism spectrum disorder (ASD), the method comprising: administering to a subject suffering from ASD a live, purified bacterial population, wherein the live, purified bacterial population comprises: a bacterial population of at least one Corynebacterium, optionally at least one Corynebacterium pseudodiphtheriae strain; and optionally at least one Coccus laziensis strain. This document further provides a method wherein ASD is autism, pervasive developmental disorder (PDD-NOS), Asperger's syndrome, childhood disintegration disorder (CDD), or Rett syndrome. This document further provides a method wherein the live, purified bacterial population is administered intranasally. This document further provides a method wherein the live, purified bacterial population is administered orally. This document further provides a method wherein the subject is an infant. This document further provides a method wherein the subject is a child. This document further provides a method wherein the subject is an adult. This document further provides a method wherein the adult is 65 years of age or older. This document further provides a method wherein the live, purified bacterial population is present in a total amount of up to 10^15 cfu. This paper further provides a method in which the live, purified bacterial population is present in a total amount of 10^3 to 10^12 cfu. This paper further provides a method in which the Corynebacterium species include: crowded Corynebacterium, non-fermenting Corynebacterium, ammonia-producing Corynebacterium, amycotic Corynebacterium, silver Corynebacterium, aquatic Corynebacterium, auricular Corynebacterium, bovine Corynebacterium, diphtheria Corynebacterium, equine Corynebacterium (now *Rhodococcus equi*), effective Corynebacterium, paleo Corynebacterium, glucosinolate Corynebacterium, glutamate Corynebacterium, granulomatous Corynebacterium, hemolytic Corynebacterium, halophyte Corynebacterium, and *Corynebacterium koraiensis*. The present invention relates to the following strains of Corynebacterium jejuni, Corynebacterium medricularis, Corynebacterium martensii, Corynebacterium microfiliis, Corynebacterium pustulosa (Propionibacterium acnes), Corynebacterium micrometabolicum, Corynebacterium propionate, Corynebacterium pseudodiphtheriae (Corynebacterium hoffmannii), Corynebacterium pseudotuberculosis, Corynebacterium sheepii, Corynebacterium pyogenes—Cryptospirosis, Corynebacterium urealyticum, Corynebacterium nephrostomyense, Corynebacterium, Corynebacterium striatum, Corynebacterium microfiliis, Corynebacterium ulcerans, Corynebacterium urealyticum, or Corynebacterium sicca. The present invention further provides a method wherein the Corynebacterium pseudodiphtheriae strain is selected from the strains listed in Table 1. The present invention further provides a method wherein *Coccidioidomyces laziensis* is selected from the strains listed in Table 2. The present invention further provides a method wherein the Corynebacterium pseudodiphtheriae strain is selected from the strains listed in Table 1, and wherein *Coccidioidomyces laziensis* is selected from the strains listed in Table 2. The present invention further provides a pharmaceutical composition comprising mixtures listed in Tables 4 to 7.
[0084] In some embodiments, this document provides a method for treating post-traumatic stress disorder (PTSD), the method comprising: administering to a subject suffering from PTSD a live, purified bacterial population, wherein the live, purified bacterial population comprises: a bacterial population of at least one Corynebacterium, optionally at least one Corynebacterium pseudodiphtheriae strain; and optionally at least one Coccidia laziensis strain. This document further provides a method wherein the live, purified bacterial population is administered intranasally. This document further provides a method wherein the live, purified bacterial population is administered orally. This document further provides a method wherein the subject is an infant. This document further provides a method wherein the subject is a child. This document further provides a method wherein the subject is an adult. This document further provides a method wherein the adult is 65 years of age or older. This document further provides a method wherein the live, purified bacterial population is present in a total quantity of up to 10^15 cfu. This document further provides a method wherein the live, purified bacterial population is present in a total quantity of 10^3 cfu to 10^12 cfu. This article further provides a method in which the *Corynebacterium* species include: *Corynebacterium claustrophoides*, *Corynebacterium non-fermenting*, *Corynebacterium ammoniagenic*, *Corynebacterium amylopectinum*, *Corynebacterium auriculatum*, *Corynebacterium bovis*, *Corynebacterium diphtheriae*, *Corynebacterium equineumoniae* (now *Rhodococcus equi*), *Corynebacterium viabilityense*, *Corynebacterium flavonoids*, *Corynebacterium glucoside*, *Corynebacterium glutamicum*, *Corynebacterium granulomatum*, *Corynebacterium hemolyticum*, *Corynebacterium halophyte*, and *Corynebacterium kurstii*. The present invention relates to the following strains of Corynebacterium jejuni, Corynebacterium medricularis, Corynebacterium martensii, Corynebacterium microfiliis, Corynebacterium pustulosa (Propionibacterium acnes), Corynebacterium micrometabolicum, Corynebacterium propionate, Corynebacterium pseudodiphtheriae (Corynebacterium hoffmannii), Corynebacterium pseudotuberculosis, Corynebacterium sheepii, Corynebacterium pyogenes—Cryptospirosis, Corynebacterium urealyticum, Corynebacterium nephrostomyense, Corynebacterium, Corynebacterium striatum, Corynebacterium microfiliis, Corynebacterium ulcerans, Corynebacterium urealyticum, or Corynebacterium sicca. The present invention further provides a method wherein the Corynebacterium pseudodiphtheriae strain is selected from the strains listed in Table 1. The present invention further provides a method wherein *Coccidioidomyces laziensis* is selected from the strains listed in Table 2. The present invention further provides a method wherein the Corynebacterium pseudodiphtheriae strain is selected from the strains listed in Table 1, and wherein *Coccidioidomyces laziensis* is selected from the strains listed in Table 2. The present invention further provides a pharmaceutical composition comprising mixtures listed in Tables 4 to 7.
[0085] In some embodiments, this document provides a method for treating anxiety disorders, the method comprising: administering to a subject suffering from an anxiety disorder a live, purified bacterial population, wherein the live, purified bacterial population comprises: a bacterial population of at least one Corynebacterium, optionally at least one Corynebacterium pseudodiphtheriae strain; and optionally at least one Coccus laziensis strain. In some embodiments, the anxiety disorder is generalized anxiety disorder, obsessive-compulsive disorder, panic disorder, post-traumatic stress disorder, or social phobia. This document further provides a method wherein the live, purified bacterial population is administered intranasally. This document further provides a method wherein the live, purified bacterial population is administered orally. This document further provides a method wherein the subject is an infant. This document further provides a method wherein the subject is a child. This document further provides a method wherein the subject is an adult. This document further provides a method wherein the adult is 65 years of age or older. This document further provides a method wherein the live, purified bacterial population is present in a total quantity of up to 10^15 cfu. This document further provides a method wherein the live, purified bacterial population is present in a total quantity of 10^3 cfu to 10^12 cfu. This article further provides a method in which the *Corynebacterium* species include: *Corynebacterium claustrophoides*, *Corynebacterium non-fermenting*, *Corynebacterium ammoniagenic*, *Corynebacterium amylopectinum*, *Corynebacterium auriculatum*, *Corynebacterium bovis*, *Corynebacterium diphtheriae*, *Corynebacterium equineumoniae* (now *Rhodococcus equi*), *Corynebacterium viabilityense*, *Corynebacterium flavonoids*, *Corynebacterium glucoside*, *Corynebacterium glutamicum*, *Corynebacterium granulomatum*, *Corynebacterium hemolyticum*, *Corynebacterium halophyte*, and *Corynebacterium kurstii*. The present invention relates to the following strains of Corynebacterium jejuni, Corynebacterium medricularis, Corynebacterium martensii, Corynebacterium microfiliis, Corynebacterium pustulosa (Propionibacterium acnes), Corynebacterium micrometabolicum, Corynebacterium propionate, Corynebacterium pseudodiphtheriae (Corynebacterium hoffmannii), Corynebacterium pseudotuberculosis, Corynebacterium sheepii, Corynebacterium pyogenes—Cryptospirosis, Corynebacterium urealyticum, Corynebacterium nephrostomyense, Corynebacterium, Corynebacterium striatum, Corynebacterium microfiliis, Corynebacterium ulcerans, Corynebacterium urealyticum, or Corynebacterium sicca. The present invention further provides a method wherein the Corynebacterium pseudodiphtheriae strain is selected from the strains listed in Table 1. The present invention further provides a method wherein *Coccidioidomyces laziensis* is selected from the strains listed in Table 2. The present invention further provides a method wherein the Corynebacterium pseudodiphtheriae strain is selected from the strains listed in Table 1, and wherein *Coccidioidomyces laziensis* is selected from the strains listed in Table 2. The present invention further provides a pharmaceutical composition comprising mixtures listed in Tables 4 to 7.
[0086] In some embodiments, this document provides a method for treating depression, the method comprising: administering to a subject suffering from depression a live, purified bacterial population, wherein the live, purified bacterial population comprises: a bacterial population of at least one Corynebacterium, optionally at least one Corynebacterium pseudodiphtheriae strain; and optionally at least one Coccus laziensis strain. This document further provides a method wherein the live, purified bacterial population is administered intranasally. This document further provides a method wherein the live, purified bacterial population is administered orally. This document further provides a method wherein the subject is an infant. This document further provides a method wherein the subject is a child. This document further provides a method wherein the subject is an adult. This document further provides a method wherein the adult is 65 years of age or older. This document further provides a method wherein the live, purified bacterial population is present in a total quantity of up to 10^15 cfu. This document further provides a method wherein the live, purified bacterial population is present in a total quantity of 10^3 cfu to 10^12 cfu. This article further provides a method in which the *Corynebacterium* species include: *Corynebacterium claustrophoides*, *Corynebacterium non-fermenting*, *Corynebacterium ammoniagenic*, *Corynebacterium amylopectinum*, *Corynebacterium auriculatum*, *Corynebacterium bovis*, *Corynebacterium diphtheriae*, *Corynebacterium equineumoniae* (now *Rhodococcus equi*), *Corynebacterium viabilityense*, *Corynebacterium flavonoids*, *Corynebacterium glucoside*, *Corynebacterium glutamicum*, *Corynebacterium granulomatum*, *Corynebacterium hemolyticum*, *Corynebacterium halophyte*, and *Corynebacterium kurstii*. The present invention relates to the following strains of Corynebacterium jejuni, Corynebacterium medricularis, Corynebacterium martensii, Corynebacterium microfiliis, Corynebacterium pustulosa (Propionibacterium acnes), Corynebacterium micrometabolicum, Corynebacterium propionate, Corynebacterium pseudodiphtheriae (Corynebacterium hoffmannii), Corynebacterium pseudotuberculosis, Corynebacterium sheepii, Corynebacterium pyogenes—Cryptospirosis, Corynebacterium urealyticum, Corynebacterium nephrostomyense, Corynebacterium, Corynebacterium striatum, Corynebacterium microfiliis, Corynebacterium ulcerans, Corynebacterium urealyticum, or Corynebacterium sicca. The present invention further provides a method wherein the Corynebacterium pseudodiphtheriae strain is selected from the strains listed in Table 1. The present invention further provides a method wherein *Coccidioidomyces laziensis* is selected from the strains listed in Table 2. The present invention further provides a method wherein the Corynebacterium pseudodiphtheriae strain is selected from the strains listed in Table 1, and wherein *Coccidioidomyces laziensis* is selected from the strains listed in Table 2. The present invention further provides a pharmaceutical composition comprising mixtures listed in Tables 4 to 7. Example
[0087] Example 1: Bacterial mixture i. Separates and mixtures. This document describes combinations of bacterial strains that can be used to generate compositions comprising pharmaceutical compositions for treating respiratory symptoms. In subsequent mixtures, each of the live, purified strains is present in the same amount of CFU as the other live, purified strains in each mixture.
[0088] First, mixtures with two strain combinations were generated. Each mixture contained two Corynebacterium strains listed in Table 1, where “X” indicates inclusion, and 44 mixtures (A1 to A44) are listed in Table 4.
[0089] Table 4.
[0090] Next, mixtures containing the two strains of Lazy Coccidia listed in Table 2, where “X” indicates inclusion, are prepared among the 66 mixtures (B1 to B66) listed in Table 5.
[0091] Table 5.
[0092] Third, each of the Corynebacterium genus mixtures listed in Table 1 is combined with one of the 12 Lazy Coccidia strains listed in Table 2, where “X” indicates inclusion, and is listed in Table 6 among the 66 mixtures (C1 to C130).
[0093] Table 6.
[0094] Fourth, prepare a mixture of various Corynebacterium strains from Table 1. In this example, 2, 3, 4, or 5 strains from different Corynebacterium species are included in the composition. The strains are selected from: Corynebacterium pseudodiphtheriae ATCC 10700 and / or JCM1320; Corynebacterium amylopectin ATCC 49358; Corynebacterium glutamicum ATCC 13032; and Corynebacterium striatum ATCC 6940. The composition may contain strains other than those from ATCC 10700 and / or JCM 1320.
[0095] Fifth, prepare a mixture of two Corynebacterium pseudodiphtheriae strains from Table 1: ATCC 10700 and JCM1320, namely "mixture D1".
[0096] Sixth, combine mixture D1 with one of the 12 strains of *Lazy Coccidia* listed in Table 2, where “X” indicates inclusion, listed in Table 7 among the 66 mixtures (E1 to E12).
[0097] Table 7.
[0098] Combine the seventh mixture of Corynebacterium species listed in Table 1 to include at least one strain of each of Corynebacterium pseudodiphtheriae, Corynebacterium crowdingii, and Corynebacterium amylopectinum. For example: ATCC 10700 and / or JCM 1320 plus ATCC 49725 and ATCC 49368.
[0099] iii. Culture from cryogenic stock solution. Bacterial strains were grown at 37°C using 5% CO2. *Lazidos nigra* strains were cultured from cryogenic stock on BBL Columbia polymyxin nalidixic acid (CNA) agar and 5% sheep blood (BD Diagnostics) for 2 days. Corynebacterium strains were cultured from cryogenic stock on BHI agar (e.g., for *Corynebacterium pseudodiphtheriae* and *Corynebacterium propionate*) or BHI agar supplemented with 1% Tween 80 (e.g., for *Corynebacterium bulgaricum*) for 1 day. Resuspension, as described below, was performed by collecting colonies from agar medium and resuspending them in 1X phosphate-buffered saline (PBS).
[0100] Example 2: MRSA Model System i. Exposure dependence determination Clinical isolates of *Corynebacterium pseudodiphtheriae* and *Corynebacterium laziness* from subjects (e.g., strains listed in Tables 1 and 2 and mixtures from Example 1) were assayed to determine whether anti-Staphylococcal activity depended on direct physical contact between the bacteria. Briefly, a sterile 0.2 μm filter tray was placed on top of BHIT agar (Brain Heart Infusion (BHI) agar (Becton Dickinson)) inoculated with one *Staphylococcus* strain from the strains provided in Table 3 (JE2, LAC, Mu50, or USA 900). Each clinical isolate in suspension was individually sampled on top of the filter tray, ensuring no physical contact between the cell suspension and the *Staphylococcus*-inoculated agar plate. The plate was incubated at 28°C, and the absence or presence of the zone of elimination (ZOC) was visually assessed at 24, 72, and 120 hours. The absence of ZOC in the presence of a filter disc indicates that physical contact is necessary for the anti-Staphylococcal activity of the most susceptible Staphylococcus aureus strain.
[0101] ii. Preparation of conditional cell-free medium (CCFM) and disk diffusion assay.Clinical isolates exhibiting contact-independent bactericidal activity against Staphylococcus aureus (e.g., strains listed in Tables 1 and 2, and mixtures from Example 1) were individually cultured overnight in 10 mL BHIT broth at 37°C with shaking at 190 rpm. The cultures were precipitated by centrifugation, and the supernatant was sterilized by filtration through a 2 μm filter (Corning). One mL of sterile supernatant was retained, and the remaining supernatant was concentrated by ammonium sulfate precipitation (50X). For heat treatment, 50 μL aliquots of unconcentrated or 50X CCFM were incubated at 90°C for 10 minutes, followed by cooling. For disk diffusion assays, the Staphylococcus aureus strain most sensitive to the corresponding inhibitory activity was cultured overnight on BHI agar at 37°C. The next day, the cells grown on the plates were recovered and diluted in BHI broth to 1 × 10^8 cells / mL (OD600 = 0.1). Then, using a sterile swab, a Staphylococcus aureus cell suspension was spread onto BHIT agar to form a bacterial growth. The plate was dried in a laminar flow hood for 30 minutes. Next, a sterile 5 mm diffusion plate was placed on top of the Staphylococcus aureus bacterial growth, and 50 μL of unconcentrated CCFM or 50X CCFM was inoculated onto the plate. The plate was incubated at 28°C, and images were taken after 72 hours of incubation.
[0102] iii. Staphylococcus aureus infection and CCFM treatment in the large wax moth caterpillar. Staphylococcus aureus strains JE2, LAC, Mu50, or USA 900 were cultured overnight on BHI agar at 37°C. The next day, Staphylococcus aureus cells were recovered and diluted in PBS to 1 × 10⁸ cells / ml (OD600 = 0.1). The total CFU was then further adjusted to obtain the desired dose; i.e., 10⁷ or 10⁶ CFU in 5 μL PBS + 0.01% bromophenol dye. For infection, large wax moth caterpillars (Vanderhorst Wholesale Inc.) were used within 1 day of receipt. Caterpillars of a dose between 200 and 300 mg were selected for infection. In short, using a 10 μL glass syringe fitted with a 31G needle (Hamilton), 5 μL of inoculum containing 10⁷ or 10⁶ total CFU of Staphylococcus aureus was injected into the last left foreleg. For caterpillars treated with CCFM using strains from Tables 1 and 2 and a mixture of those from Example 1, the caterpillars were maintained at room temperature for 1 hour after injection of Staphylococcus aureus, then refrigerated at 4°C for 12 minutes, and subsequently injected with 5 μL of freshly prepared 50X CCFM or 50X concentrated BHIT (sham-operated) from the clinical isolate (treated). These injections were performed in the last right foreleg. All caterpillars were incubated at 37°C, and survival was monitored over 120 hours. Caterpillars containing untreated and PBS-injected caterpillars served as controls.
[0103] iv. Assay for intranasal colonization of methicillin-resistant Staphylococcus aureus in mice.Staphylococcus aureus strains JE2, LAC, Mu50, or USA 900 were cultured at 37°C in Todd-Hewitt broth (THB) or Todd-Hewitt agar (THA) (Difco). Brain-Heart Infusion (BHI) broth and agar (Difco) were used to culture strains of Corynebacterium pseudodiphtheriae and Coccidia laziensis (e.g., strains listed in Tables 1, 2, and Example 1). CD1 mice were obtained (Charles River Laboratories, Wilmington, MA). Mice were intranasally inoculated with 10 µl drops of the specified concentration of inoculum. Mice were administered a total of 1 × 10^9 CFU of bacteria. CD1 mice were intranasally inoculated with: (i) Corynebacterium pseudodiphtheriae; (ii) Coccidia laziensis; (iii) Corynebacterium pseudodiphtheriae and Coccidia laziensis or (iv) PBS. Two days later, mice were administered streptomycin-resistant MRSA (JE2, LAC, Mu50, or USA 900) intranasally and sacrificed two days later. For bacterial counting, isoflurane was used, followed by euthanasia via cervical dislocation, and nasal tissue was homogenized and vortexed in PBS for 5 minutes. The homogenate was then plated onto THA with or without streptomycin after appropriate serial dilutions. Bacterial identification was based on antibiotic resistance patterns, colony morphology, and color.
[0104] Example 3: Pneumonia Model System i . Growth assay of Streptococcus pneumoniae in cell-free liquid culture medium. After growth in BHI, *Coccidioidomyces laziensis* or *Corynebacterium pseudodiphtheriae* cells (e.g., from strains listed in Tables 1 and 2, and mixtures from Example 1) were removed using a 0.22 μM sterile filter to produce cell-free conditioned medium (CFCM). The pH of the CFCM was adjusted using 2 N H₂SO₄ and 10 M KOH to match the pH of the BHI broth alone within 0.02 pH units. *Streptococcus pneumoniae* strains TIGR4, DBL5, and M270-8 (see Table 3) were each grown on BBL Columbia CNA agar containing 5% sheep blood for 1 day, collected with sterile swabs, resuspended in 1x PBS to an OD₆₀ of 0.30, inoculated 1:100 into *Coccidioidomyces laziensis* or *Corynebacterium pseudodiphtheriae* CFCM and BHI broth, and grown in static (*Streptococcus pneumoniae*) cultures at 37°C under atmospheric conditions for 19–20 hours. The growth yield was quantified as OD600 absorbance.
[0105] ii. Growth assay of Streptococcus pneumoniae under single culture medium and co-culture medium conditions.*Lazy Coccidia laziensis* and *Corynebacterium pseudodiphtheriae* strains (e.g., strains listed in Tables 1 and 2, and mixtures from Example 1) were grown from frozen stock solutions. Cells were collected using sterile swabs and resuspended in sterile PBS to an OD600 nm of 0.5. Cells were then spotted onto polycarbonate membranes on BHI agar medium containing 400 U / mL bovine liver catalase in a 1:1 resuspension. After 2 days of growth, the polycarbonate membranes containing *Lazy Coccidia laziensis* and / or *Corynebacterium pseudodiphtheriae* were removed from each plate, leaving cell-free conditioned agar medium. *Streptococcus pneumoniae* was grown overnight on BBL Columbia CNA agar containing 5% sheep blood using sterile swabs, the bacterial colony was streaked onto cell-free conditioned agar medium and allowed to grow for 24 hours. Growth / inhibition was assessed daily and photographic records were taken.
[0106] iii. Mouse model. Immediately before surgery, 6- to 8-week-old FVB / N mice were orally fed 200 µL of (i) *Corynebacterium pseudodiphtheriae*; (ii) *Coccidioidomyces laziensis*; (iii) *Corynebacterium pseudodiphtheriae* and *Coccidioidomyces laziensis* (e.g., strains listed in Tables 1 and 2, and mixtures from Example 1) or (iv) sterile water (medium) (for bacteria: 1 × 10^9 colony-forming units (CFU) / mL). Pneumonia was induced by direct intratracheal instillation of *Pseudomonas aeruginosa* (ATCC 27853) or *Streptococcus pneumoniae* (TIGR4, M270-8, or DBL5). Under isoflurane anesthesia, mice underwent a midline cervical incision, and *Pseudomonas aeruginosa* or *Streptococcus pneumoniae* was introduced into the trachea using a 29-gauge syringe. Forty µL of 4 × 10^8 CFU of bacteria diluted in sterile saline was used. The mice were then held upright for 5 seconds to enhance delivery into the lungs. The sham-operated mice underwent the same treatment except that they received intratracheal injections of saline. All mice received antibiotic therapy (gentamicin 0.2 mg / mL, subcutaneously) postoperatively to simulate a clinical environment. Animals were euthanized at 12 or 24 hours (for acute studies) or 7 days (for survival). For acute studies, mice received a single dose of (i) *Corynebacterium pseudodiphtheriae*; (ii) *Coccidioidomyces laziensis* or (iii) both *Corynebacterium pseudodiphtheriae* and *Coccidioidomyces laziensis*. For survival studies, mice were treated daily with (i) *Corynebacterium pseudodiphtheriae*; (ii) *Coccidioidomyces laziensis* or (iii) both *Corynebacterium pseudodiphtheriae* and *Coccidioidomyces laziensis* for 7 days, with antibiotic treatment at 0, 12, and 24 hours. The presence of *Pseudomonas aeruginosa* or *Streptococcus pneumoniae* was examined in the lungs.
[0107] Example 4: Rhinitis Model System Two-month-old female BALB / cA mice were used. Animals were fed a standard rodent diet in a temperature-controlled chamber with a 12-hour light / dark cycle (23°C). Immune responses in mice were suppressed by subcutaneous injection of hydrocortisone (hydrocortisone hemisuccinate 100, Polfa, PL, Poland, 100 mg / kg / day) on days 0 and 4. Staphylococcus aureus (JE2, LAC, Mu50, or USA 900) was administered intranasally on day 5. Bacterial treatment was performed on day 10. Forty μL of 4 × 10⁸ CFU of bacteria diluted in sterile saline was used. Mice received a single dose of (i) *Corynebacterium pseudodiphtheriae*; (ii) *Coccidioidomyces laziensis*; or (iii) *Corynebacterium pseudodiphtheriae* and *Coccidioidomyces laziensis* (e.g., strains listed in Tables 1 and 2, and mixtures from Example 1) or (iv) saline (medium). Animals were euthanized after 12 or 24 hours or 7 days (for surviving animals), and tissue samples were collected. The presence of Staphylococcus aureus was tested in blood and internal organ samples (e.g., lungs, kidneys, liver, and spleen); the presence of Staphylococcus aureus was also tested in nasal epithelium in both control and experimental animals.
[0108] Example 5: Allergic Asthma Model System i. Mouse model of allergic asthma Female C57BL / 6 mice (Charles River), aged 6–8 weeks, were housed in a laminar flow chamber under constant temperature and humidity, with free access to food and water. Mice were treated with vancomycin and / or neomycin (5 days / week, 12-hour intervals) or bacteria ((i) Corynebacterium pseudodiphtheriae; (ii) Coccidia laziensis or (iii) Corynebacterium pseudodiphtheriae and Coccidia laziensis (e.g., strains listed in Tables 1 and 2 and mixtures from Example 1)) (3 times / week), starting 2 weeks before intravenous injection of 5 × 10^5 B16 melanoma cells and continuing throughout the experiment.
[0109] To deplete effector cells, mice were intravenously injected with a CD3 F(ab')2 fragment (145-2C11 f(ab')2) (BioXcell) at a dose of 50 μg / day, starting one day before tumor injection, for 5 days / week to deplete T cells. Alternatively, 500 μg of α-NK1.1 antibody (PK136) (BioXcell) was injected intraperitoneally (ip) one day before tumor injection, followed by 200 μg every 5 days to deplete NK cells throughout the experiment. The efficacy of cell depletion was validated by staining a specific subset of peripheral blood leukocytes after depletion. In the treatment experiments, mice were intravenously injected with 5 × 10^5 B16 melanoma cells and treated with antibiotics (vancomycin and neomycin) or probiotics ((i) Corynebacterium pseudodiphtheriae; (ii) Coccidia laziensis or (iii) Corynebacterium pseudodiphtheriae and Coccidia laziensis) alone or in combination with DTIC administered intraperitoneally at 70 mg / kg (5 days / week) starting 7 days after tumor cell injection. Mice were weighed twice weekly and euthanized on day 21 after tumor injection to count gross lung metastases.
[0110] Example 6: Asthma Model System i. Acute asthma model system. Six-week-old female BALB / c mice were sensitized by intraperitoneal (ip) administration of a mixture of ovalbumin (OVA; 10 µg, Grade V; Sigma Chemical Co., St. Louis, MO, USA) and alum (2.25 mg; Impject; Pierce, Rockford, IL, USA)). A second administration of the mixture was given one week after the first sensitization. Seven days later, the mice were challenged by inhaling 1% OVA for 30 minutes daily for three consecutive days via an ultrasonic nebulizer (Nescosonic UN-511; Alfresa, Osaka, Japan). From one week prior to initial sensitization until the study endpoint, mice were intranasally administered 1 × 10^9 colony-forming units / mouse / day of bacteria (i) *Corynebacterium pseudodiphtheriae*; (ii) *Coccidioidomyces laziensis*; or (iii) *Corynebacterium pseudodiphtheriae* and *Coccidioidomyces laziensis* (e.g., strains listed in Tables 1 and 2, and mixtures from Example 1) or (iv) PBS (mediator). Negative controls received saline instead of OVA during sensitization and airway challenge. Positive controls received nothing after OVA sensitization.
[0111] In vivo clinical evaluation.Airway hyperresponsiveness (AHR) in response to inhaled methacholine (MeCh; Sigma Chemicals) administered 24 hours after OVA challenge was measured in conscious, unrestrained mice using a pneumatic whole-body plethysmography (Buxco; EMKA Technologies, Paris, France). Briefly, mice were placed in a whole-body chamber, and baseline readings were obtained over 3 minutes and averaged. After each MeCh inhalation, nebulized saline was inhaled, followed by 5–50 mg / mL MeCh over 3 minutes. Treg cells were depleted using an anti-CD25 monoclonal antibody (mAb). Briefly, one day prior to 1% OVA challenge, mice were intraperitoneally administered 400 µL of normal saline containing 250 µg of rat anti-mouse CD25 mAb (clone PC61; eBioscience, San Diego, CA, USA). Control mice were injected with 250 µg of rat IgG1 (Sigma Chemicals).
[0112] Bronchoalveolar lavage (BAL) fluid analysis. After measuring AHR, mice were anesthetized by intraperitoneal administration of ketamine-toluidine and the trachea was immediately exposed. The airway was lavaged through endotracheal intubation, twice with 1 mL aliquots of warmed, 37°C pyrothermal saline. The recovered lavage fluid was collected, and cells were collected by centrifugation (5,000 rpm, 4°C, 5 min) and resuspended in 100 mL of cold PBS. Cell viability was determined by trypan blue staining, and total nucleated cells were counted using a hemocytometer.
[0113] For differential BAL cell counting, cell centrifugation smears were prepared and stained with Diff-Quik (Sysmex, Takatsukadai, Japan). After sample coding, all cell centrifugation smears were evaluated using an oil immersion microscope (magnification, ×1,000). At least 200 cells were counted for each preparation, and the absolute number of each cell type was calculated.
[0114] Serum IgG analysis.Serum was obtained from blood collected during exsanguination of mice following airway measurements, and 100 µL (1 / 10 dilution in carbonate-bicarbonate buffer) was added to each well of a 96-well plate. Total IgE in the serum was quantified using an IgE-specific enzyme-linked immunosorbent assay (ELISA) with matched antibody pairs (eBioSciences) according to the manufacturer's instructions. For the ELISA, the 96-well plate was first coated overnight with rat anti-mouse IgE (10 µL in 100 µL PBS; PharMingen, San Diego, CA, USA), rat anti-mouse IgG1 (20 µg in 100 µL PBS; PharMingen), or rat anti-mouse IgG2a (20 µg in 100 µL PBS; PharMingen). Remaining binding sites were blocked, and the plate was incubated with 100 µL of diluted serum (1:5 for IgE, 1:10 for IgG1 or IgG2a). After washing the plate, each of the following was added, incubated, and removed by washing in sequence: OVA (1 µg / 100 µL), peroxidase-labeled rabbit anti-OVA Ig (240 ng / 100 µL, PharMingen), and 3,3,5,5-tetramethylbenzidine solution (Sigma Chemicals). Optical density was measured at 450 nm, and Ig levels were determined relative to the level in the serum reference pool of OVA-sensitized BALB / c mice (specified value: 100 experimental units / mL).
[0115] Cytokine assay A commercial formulation of paired antibodies and protein standards for measuring mouse IL-4, IL-5, IL-13 and IFN-γ (eBioSciences) in serum was developed for use in ELISA development according to the manufacturer’s instructions.
[0116] Lymphocyte proliferation assay. Following BAL, the mouse spleen was removed. Mouse spleen cells were separated using a Histopaque (Sigma Chemicals) gradient, and the collected cells were washed with PBS. RBCs were lysed by gently mixing the cells with 3.6 mL of 0.24% NaCl for 20 seconds, followed by rapid addition of 0.3 mL of 8.7% NaCl and further dilution with PBS. The pellet was resuspended in Iskov's Modified Dalberg's Medium (IMDM) and incubated overnight at 4°C. The following morning, the cells were centrifuged at 4°C, resuspended in cold PBS, stained with trypan blue, and counted using a hemocytometer.
[0117] Splenic T cells were cultured in IMDM supplemented with 25 mM HEPES, 10% (v / v) heat-inactivated fetal bovine serum (FBS), 60 mg / L (100 U / mL) penicillin, 100 mg / L streptomycin, and 0.29 g / L L-glutamine. Splenic T cells were adjusted to 1 × 10^5 cells / 200 µL / well, transferred to 96-well plates, and incubated at 37°C in a humidified 5% CO2 incubator for 72 h. Cells were stimulated with OVA (100 µg / mL) for 72 h. Twelve h before the end of incubation, 1 µCi of [3H]-thymidine was added to each well. Cells were collected onto glass microfiber filters (Simport, Beloeil, Canada) and radioactivity was measured using a liquid scintillation counter. Incorporation (counted per minute) during the last 12 h of culture was used as the proliferation index.
[0118] Flow cytometry. According to the manufacturer's instructions, mouse Treg cells were collected from the spleen, and CD4+CD25+Foxp3+ expression was analyzed using a mouse Treg cell staining kit containing FITC-labeled anti-CD4, APC-labeled anti-CD25, and PE-labeled anti-Foxp3 (eBioSciences). Briefly, the prepared cells (1 × 10^6) were washed with cold PBS by centrifugation, resuspended in 1 mL of fixation / permeabilization solution, and incubated in the dark at 4°C for 30–60 min. The cells were washed once with 2 mL of permeabilization buffer, collected by centrifugation, resuspended in 20 mL of permeabilization buffer containing a blocking agent (2% (2 mL) of normal rat serum) and incubated in the dark at 4°C for 15 min. Next, 20 mL of permeabilization buffer containing a fluorescent dye-conjugated antibody or isotype control was added, followed by incubation in the dark at 4°C for 30 min. Finally, the cells were washed with 2 mL of permeabilization buffer, resuspended in flow cytometry buffer (PBS with 2% FBS), and analyzed by flow cytometry using FACSCalibur with CellQuest software (BD Biosciences, Mountain View, CA, USA).
[0119] Lung histopathology.For histological evaluation of lung tissue, the left lung of each mouse was embedded in paraffin, sectioned at a thickness of 5 µm, and stained with hematoxylin and eosin (H&E) to assess eosinophilic infiltration. Inflammation was scored. The degree of peribronchial and perivascular inflammation was assessed using a subjective scale of 0–3. Cellular infiltration in five randomly selected fields of view was evaluated under a Zeiss Axiophot microscope (magnification, ×100; Carl Zeiss, Inc., Thornwood, NY, USA).
[0120] ii. A mouse model of allergic asthma induced by birch pollen. Mice were intranasally administered the following: (i) *Corynebacterium pseudodiphtheriae*; (ii) *Coccidioidomyces laziensis*; or (iii) *Corynebacterium pseudodiphtheriae* and *Coccidioidomyces laziensis* (e.g., strains listed in Tables 1 and 2 and mixtures from Example 1) or (iv) PBS (mediator), eight times at 5 × 10^8 CFU / dose on days 1–4 and 8–11, followed by a 2-week asthma induction protocol using birch pollen extract every other day. The efficacy of prophylactic treatment was analyzed based on serum antibody levels, bronchoalveolar lavage cell counts, lung histology, lung cytokine levels, and airway hyperresponsiveness. Colonization and translocation of the administered bacteria were assessed by bacterial cell counts in nasal mucosa, fecal samples, cervical lymph nodes, and blood.
[0121] Example 7: COPD Model System COPD was induced in C57Bl / 6 mice by inhalation of cigarette smoke from 14 cigarettes twice daily for 7 days over 60 days. During the same period, mice were intranasally administered 1 × 10^8 colony-forming units / mouse / day of bacteria (i) *Corynebacterium pseudodiphtheriae*; (ii) *Coccidioidomyces laziensis*; or (iii) *Corynebacterium pseudodiphtheriae* and *Coccidioidomyces laziensis* (e.g., strains listed in Tables 1 and 2 and mixtures from Example 1) or (iv) PBS (mediator). Pro-inflammatory mediators IL-6, TNF, IL-1β, CXCL1, CXCL8, CXCL10, KC, CXCL9, CXCL11, and the anti-inflammatory mediator IL-10 in bronchoalveolar lavage fluid (BALF) were measured by ELISA. MMP9, as well as MMP12, NF-κB, STAT3, and TLRs 2, 4, and 9, were analyzed in the lungs by quantitative RT-PCR. NF-κB was also analyzed by immunolocalization. Lung tissue is used for histological and morphological analysis.
[0122] Example 8: Influenza Model System Seven-week-old female BALB / c mice were purchased from SLC Co., Ltd. (Hamamatsu, Japan). Mice were housed at 23–25°C under a 12-hour light / dark cycle and fed a standard laboratory rodent diet (Oriental Yeast, Tokyo, Japan). Mice were randomly assigned to a control group (virus infection only) and three treatment groups (infected mice treated with (i) Corynebacterium pseudodiphtheriae; (ii) Coccidia laziensis; or (iii) both Corynebacterium pseudodiphtheriae and Coccidia laziensis) (e.g., strains listed in Tables 1 and 2 and mixtures from Example 1). Mice were administered intranasally at a dose of 1 × 10^8 colony-forming units / 600 µL / mouse / day for three days.
[0123] Influenza A / PR / 8 / 34 (PR8, H1N1) virus was cultured in the allantoic fluid of 11-day-old chicken embryos at 34°C for 2 days. The allantoic fluid was removed and stored at -80°C. For PR8, the viral titer in the allantoic fluid is expressed as the 50% tissue culture infectious dose (TCID50). The PR8 viral titer in the allantoic fluid was 10^7.4 TCID50 / ml.
[0124] Mice were infected with the PR8 virus. In short, mice were anesthetized by intraperitoneal injection of sodium amobarbital (0.25 mg per mouse) on the second day after three consecutive days of intranasal administration of the treated bacterial solution, and then infected by instilling 1 μl of PR8 into each nostril (2 μl per mouse). To examine the survival rate of mice inoculated with the PR8 solution, 10 μl of PBS (20 μl per mouse) was administered intranasally for 3 days after PR8 inoculation. Morbidity and mortality were observed in infected mice for 2 weeks. Morbidity was assessed by fur wrinkling, slow movement, and weight loss.
[0125] Mice were anesthetized with ether and euthanized the day after exsanguination. Lungs were removed, finely chopped, and incubated with 300 U collagenase (Yakult Honsha Co., Tokyo, Japan) in 15 ml RPMI 1640 medium (Sigma-Aldrich, Tokyo, Japan) for 90 minutes. To separate the tissue into single cells, the collagenase-treated, chopped lung was gently tapped into a plastic dish. After removing debris, red blood cells were depleted by hypotonic lysis. Cells were washed with RPMI medium supplemented with 100 U penicillin and 100 mg streptomycin per ml, and then resuspended in medium supplemented with 10% heat-inactivated fetal bovine serum (FCS). Cells were counted using the trypan blue exclusion method and then resuspended at an appropriate concentration of 5 × 10^6 cells per ml.
[0126] The cytotoxic activity of isolated lung cells was analyzed in a natural killer (NK) cell cytotoxicity assay. Briefly, YAC-1 cells were first labeled with 3,3'-dioctadecyloxacarbonylcyanine perchlorate (Dio) (Molecular Probes, Eugene, OR, USA) at a concentration of 1.0 × 10^6 cells per μl and incubated in a CO2 incubator for 10 minutes. The Dio-labeled YAC-1 cells were then mixed with propidium iodide (PI) (Molecular Probes) at a concentration of 1.0 × 10^6 cells per ml. An appropriate number of lung cells were added to 2 × 10^4 Dio-labeled and PI-stained YAC-1 cells in a 96-part microtiter plate (Corning Hydraulics, NY, USA) containing 10% FCS in a total volume of 0.1 ml. The plate was then incubated at 750 °C. g Gently centrifuge for 3 minutes, then incubate at 37°C in 5% CO2 for 4 hours. After incubation, mix the cultured cells with 400 μl PBS in a tube and analyze by flow cytometry.
[0127] Lungs were harvested on day 4. Total RNA was isolated using the FastPure Isolation Kit (Takara Bio Inc., Ohtsu, Japan). Reverse transcription was performed using the PrimeScript RT Kit (Takara Bio Inc.). The mRNA levels of interferon (IFN)-α, IFN-β, IFN-γ, interleukin (IL)-1β, IL-12, IL-18, tumor necrosis factor (TNF), and monocyte chemoattractant protein (MCP)-1 were determined using quantitative RT-PCR. Fluorescent reporter genes were detected using the Dice Real-Time System (Takara Bio Inc.), and primers were designed using the Perfect Real-Time Support System (Takara Bio Inc.). Actin-β mRNA levels were measured in all samples to normalize gene expression. All data are expressed as fold induction compared to data obtained from control mice.
[0128] Example 9: Idiopathic Pulmonary Fibrosis (IPF) Model System Eight to ten-week-old C57BL / 6J mice were purchased from The Jackson Laboratory and housed under specific pathogen-free conditions. Germ-free (GF) mice with a C57BL / 6 background were housed. Bleomycin was delivered to the oropharynx of the mice to induce acute inflammation (days 0–7), fibrosis (days 7–14), and fibrosis (days 14–21). Bleomycin-treated mice were randomly assigned to a control group (PBS only) and three treatment groups (treated with (i) Corynebacterium pseudodiphtheriae; (ii) Coccidia laziensis or (iii) both Corynebacterium pseudodiphtheriae and Coccidia laziensis) (e.g., mice treated with bleomycin from the strains listed in Tables 1 and 2 and mixtures from Example 1). Mice were intranasally administered 20 μl of the treated bacterial solution at a concentration of 10 mg / ml (200 μg per mouse) three times daily for three consecutive days. Tissue collection (including lungs), processing, and staining were performed. Collagen deposition was measured using a hydroxyproline assay. Genomic DNA was extracted from mouse lung tissue and human bronchoalveolar lavage fluid. In vivo lung inflammation was assessed using cytokine measurements from human BALF and mouse lung homogenates via the Luminex platform (MilliporeSigma).
[0129] Example 10: Olfactory Nerve Infection Model System Bacterial strains. Burkholderia pseudomeliformis strain MSHR520 was a clinical isolate from human meliformis cases. Allelic substitution mutants of MSHR520 lacking a capsule (MSHR520ΔCap) were generated. Clinical isolates of Corynebacterium pseudodiphtheriae (Table 1) and Coccidia laziensis (Table 2) were also prepared.
[0130] Mice. S100β-DsRed transgenic reporter mice were obtained, in which the human S100β promoter drives the expression of DsRed fluorescent protein, causing cells expressing the S100β promoter to express DsRed in the cytoplasm. In these mice, glial cells containing olfactory ensheathing cells (OECs) and Schwann cells of other peripheral nerves express DsRed protein.
[0131] i. Methimazole treatment and intranasal inoculation. S100β-DsRed mice aged 5 to 10 weeks were injected intraperitoneally with methimazole (Sigma-Aldrich, phosphate-buffered saline, PBS 50 mg / kg, 10 mg / ml) or a mordant (PBS). Three days later, the animals were intranasally inoculated with MSHR520ΔCap or the mordant. A small amount of cryopreservative (-80°C, in 20% glycerol; 10–50 μl) was streaked onto LB agar containing streptomycin (100 μg / ml), incubated at 30°C for several days, and single colonies were inoculated into liquid RB broth and grown by shaking at 37°C for 16 hours to reach the stable phase. A portion was used for live cell count (CFU) assay on LB agar to ensure that the inoculum used was consistently a total of 3 × 10^5 cells, which were resuspended in PBS and delivered as 10 μl drops / nasal cavity. Isolates D1-D30 of *Corynebacterium pseudodiphtheriae* and *C. laziensis* were prepared as described in Example 2, totaling 1 × 10^8 cells, which were resuspended in PBS and delivered as 10 μl drops / nasal cavity. Intranasal administration to mice was performed three times daily for three days: (i) *Corynebacterium pseudodiphtheriae*; (ii) *C. laziensis*; (iii) *C. laziensis* / *Corynebacterium pseudodiphtheriae* or (iv) PBS. Five days later, mice were administered: (i) control (PBS injection + PBS inoculation); (ii) methimazole alone (methimazole injection + PBS inoculation); (iii) *Corynebacterium pseudodiphtheriae* alone (PBS injection + *Corynebacterium pseudodiphtheriae* inoculation); (iv) methimazole + *Burkholderia pseudomereus* group (methimazole injection + *Burkholderia pseudomereus* inoculation).
[0132] Animals were housed in individually ventilated HEPA-filtered cages (IsoCage N Bioprotection, Tecniplast) with aspen bedding. They were provided with food pellets (standard rat and mouse feed, Speciality Feeds) and water at will. Cage conditions were maintained at constant temperature (19–23°C) and humidity (40–60%), with a 12-hour light and 12-hour dark cycle.
[0133] Tissue preparation. Seven days after intranasal inoculation with methimazole / Burkholderia pseudomallei, mice were euthanized by lethal intraperitoneal injection of sodium pentobarbital (Lethabarb). The heads were fixed overnight at 4°C in PBS containing 4% paraformaldehyde (PFA), followed by decalcification in 20% EDTA for four weeks. The heads were then embedded in optimal cutting temperature (OCT) medium (ProSciTech) and frozen. Coronal sections (50 μm) were cut using a cryostat (Leica CM1860).
[0134] Immunohistochemistry. Rabbit anti-Burkholderia pseudomereus (1:2,000) was used to label Burkholderia pseudomereus. This antibody was generated against the sarcodyl-insoluble fraction rich in outer membrane proteins (RRID: AB_2736920). The secondary antibody was donkey anti-rabbit Alexa Fluor 488 (Abcam ab150073; 1:300). Class III β-tubulin was detected using rabbit anti-β III tubulin (Abcam ab18207; 1:200); the secondary antibody was donkey anti-rabbit Alexa Fluor 647 (Thermofisher A31573; 1:400). The antibodies were diluted in PBS containing 2% bovine serum albumin (BSA) and 0.3% Triton X-100 (TX). Cryostat sections were first incubated with 2% BSA / TX / PBS at room temperature for 60 minutes, followed by overnight incubation with the primary antibody at 4°C. The slides were washed and incubated with secondary antibodies for 1 hour. Cell nuclei were stained with 4',6-diamidinyl-2-phenylindole (DAPI). Images were captured using epifluorescence microscopy and laser scanning confocal microscopy. The presence of bacteria in the olfactory epithelium, olfactory nerve, and olfactory bulb was detected.
[0135] Example 11: Autism Spectrum Disorder Model System mice Adult mice of both sexes (2-4 months old) were used. Experimental. Cntnap2 and Shank3 Mice were obtained through heterozygous-to-heterozygous breeding, resulting in litters containing wild-type (WT;+ / +), heterozygous (HET;+ / -), and homozygous (KO;- / -) mice. Primitive breeding mice were obtained from the Jackson Laboratory (Bozdagi et al. 2010; Poliak et al. 2003).
[0136] AAV-GCaMP6 injection.Following the method described by Kuhlman and Huang (2008), AAV2 / 1.Syn.GCaMP6f.WPRE.SV40 (Penn VectorCore, University of Pennsylvania; titer approximately 2 × 10^13 GC / mL, volume approximately 0.1 µL) was injected into the dorsal olfactory bulb using Picospritzer III. A glass pipette (tip size approximately 10 µm) was lowered through a pore in the skull to approximately 300 µm below the pia mater surface; 20 pulses (approximately 10 ms long) were injected at a pressure of 0.3 Hz, and then the pipette was retracted 50 µm towards the surface and the injection was repeated at each site as before. This sequence was repeated until the pipette reached approximately 50 µm below the surface. This injection protocol resulted in extensive and dense expression of GCaMP6 in the cell bodies and dendritic processes of the mitral valve and cluster cells. Viral expression was allowed to persist for 2 to 3 weeks post-injection before craniotomy and imaging.
[0137] WT and KO mice were randomly assigned to a control group (PBS only) and three treatment groups: (i) Corynebacterium pseudodiphtheriae; (ii) Coccidia laziensis; or (iii) Corynebacterium pseudodiphtheriae and Coccidia laziensis (e.g., strains listed in Tables 1 and 2 and mixtures from Example 1). Mice were administered intranasally at a dose of 1 × 10^8 colony-forming units / 600 µL / mouse / day for three days.
[0138] In vivo two-photon calcium imaging.Mice were anesthetized with ketamine (20 mg / mL) and toluenethiazide (3.3 mg / mL), followed by ketamine supplementation. Ketamine (20 mg / mL) was re-injected every 30 minutes to maintain a stable level of anesthesia throughout the surgery and imaging process (6–7 hours). A window (1 mm × 1 mm) was created on the left dorsal olfactory bulb of the mouse and covered with a 1.5-gauge coverslip (Zeiss) sealed with dental acrylic. A thin layer of low-melting-point agarose gel was placed between the craniotomy and the coverslip to reduce movement during imaging. The craniotomy was performed on the same area of the animal's dorsal surface to ensure consistent placement for glomerular sampling. Two-photon imaging of the glomerular dendritic process was performed on head-fixed mice using a Chameleon UltraII laser tuned to 935 nm and an in vivo two-photon platform from Intelligent Imaging Innovations (3I) with Zeiss W-plane apochromatic ×20 / 1.0 objectives. Data analysis of GCaMP6 activity was performed within a single glomerulus. Since GCaMP6 is widely expressed in all layers of the major olfactory bulb (MOB), GCaMP6 activity recorded in superficial glomeruli was considered population activity and could be attributed to various cell types. A 1-minute video was captured prior to each odor presentation to assess the spontaneous event rate. For each odor presentation trial, a 20-second video was collected at a frequency of 4.7 Hz in Slidebook 5.5 (3I), capturing 5 seconds of baseline and 15 seconds of post-stimulation fluorescence activity. The imaging field resolution was 200 × 200 pixels^2, corresponding to a 520 × 520 μm^2 window. The localization of the cranial window under the microscope was consistent, allowing for similar dorsal field-of-view partitioning in animals.
[0139] The odor is pungent.A brief pulse of isoamyl acetate (IAA; 100% saturated vapor, flow rate approximately 7.5 L / min) was delivered to anesthetized mice via a custom-designed olfactory meter through the left nostril of the animal. The odor pulse was controlled by a valve (Lee Valves) that opened via a transistor-transistor logic pulse. In each experiment and animal, the distance from the tube outlet to the nostril was maintained at approximately 5 mm. The stimulus consisted of a single pulse of IAA. In the initial tests, the stimulus duration varied between 5 and 1,000 ms. Single-trial responses of multiple glomeruli in the field of vision were obtained over a series of stimulus durations to establish a relationship between stimulus duration and glomerular activation fractions. In a typical experiment, a 200 ms stimulus was presented first, followed by a 20 ms stimulus, followed by intervals of 1.5–2 minutes, for 15 trials. Photoionization detector (PID) measurements of the odor plume were collected using a MiniRAE 3000 (RAE Systems, Inc., Sunnyvale, CA). The PID was placed approximately 5 mm from the end of the pipe. This distance was designed to simulate the distance from the pipe to an animal's nostril. The PID measurements were digitized at 10 kHz using an ITC-18 (InstruTECH) controlled by custom software written by IgorPro (Wavemetrics).
[0140] Example 12: Parkinson's Disease Model System Male C57BL / 6 mice aged 4 weeks and 2 months were used. Fifteen mice were used in each group. All mice were housed in a pathogen-free environment, randomly fed with food and water, and fed in a temperature-controlled room (25±2℃) with a 12 / 12-hour light / dark cycle for 1 week prior to experimental procedures.
[0141] From one week prior to MPTP sensitization until the study endpoint, mice were intranasally administered 1 × 10^9 colony-forming units / mouse / day of bacteria (i) *Corynebacterium pseudodiphtheriae*; (ii) *Coccidioidomyces laziensis*; or (iii) *Corynebacterium pseudodiphtheriae* and *Coccidioidomyces laziensis* (e.g., strains listed in Tables 1 and 2, and mixtures from Example 1) or (iv) PBS (mediator). Mice received MPTP (1 mg / nasal cavity) from Sigma-Aldrich, Inc., USA. One month after MPTP administration, motor behavior was analyzed using a rotating rod test and a pole-climbing test.
[0142] Rotating bar test.All sessions were conducted within the designated timeframe (8:00 AM and 12:00 PM). To learn how to maintain balance, mice were first trained for 300 seconds on a slowly rotating bar (16 rpm). One hour later, the mice were placed back on the bar, and the time it took for them to fall off the bar with continuously accelerating rotation (waiting time) was measured (increasing by 30 seconds, from 16 rpm to 32 rpm over 5 minutes). Combined measurements of the rotating bar performance for each mouse were generated as the area under the mean time curve on the bar versus rotational speed (Overall Bar Performance Score, ORP).
[0143] Pole climbing test. To assess bradykinesia in mice, a pole-climbing test was performed. Mice were placed on top of a pole (10 mm in diameter and 58 cm high) perpendicular to a rough surface. The time to turn and reach the floor was recorded. Two days prior to the test, each mouse was trained to climb the pole. On the day of the test, mice were allowed five attempts, followed by three, each lasting a maximum of four minutes.
[0144] Example 13: Lung Cancer Model System i. Mouse model Female C57BL / 6 mice (Charles River) aged 6–8 weeks were housed in a laminar flow chamber under constant temperature and humidity, with free access to food and water. Mice were treated with vancomycin and / or neomycin (5 days / week, 12-hour intervals) or bacteria ((i) Corynebacterium pseudodiphtheriae; (ii) Coccidia laziensis or (iii) Corynebacterium pseudodiphtheriae and Coccidia laziensis) (e.g., strains listed in Tables 1 and 2 and mixtures from Example 1) (3 times / week), starting 2 weeks before intravenous injection of 5 × 10^5 B16 melanoma cells and continuing throughout the experiment.
[0145] To deplete effector cells, mice were intravenously injected with a CD3 F(ab')2 fragment (145-2C11 f(ab')2) (BioXcell) at a dose of 50 μg / day, starting one day before tumor injection, for 5 days / week to deplete T cells. Alternatively, 500 μg of α-NK1.1 antibody (PK136) (BioXcell) was injected intraperitoneally (ip) one day before tumor injection, followed by 200 μg every 5 days to deplete NK cells throughout the experiment. The efficacy of cell depletion was verified by staining a specific subset of peripheral blood leukocytes after depletion. In the treatment experiment, mice were intravenously injected with 5 × 10^5 B16 melanoma cells and treated with antibiotics (vancomycin and neomycin) or probiotics ((i) Corynebacterium pseudodiphtheriae; (ii) Coccidia laziensis or (iii) Corynebacterium pseudodiphtheriae and Coccidia laziensis) alone or in combination with DTIC administered intraperitoneally at 70 mg / kg (5 days / week) starting 7 days after tumor cell injection. Mice were weighed twice a week and euthanized on day 21 after tumor injection to count gross lung metastases.
[0146] ii. Sheep model. Obtain adult female sheep (Highlander, Scotland). n = 1; Scottish blackface. n = 7; Scotch Mule. n = 1), weighing 39-65 kg, and diagnosed with spontaneously occurring preclinical OPA. Sheep were allowed to sleep on straw in groups of at least two, with free access to food and water, and given at least a 24-hour acclimatization period before anesthesia.
[0147] Subjects were randomly assigned to a control group (PBS only) and three treatment groups (infected with (i) *Corynebacterium pseudodiphtheriae*; (ii) *Coccidioidomyces laziensis*; or (iii) both *Corynebacterium pseudodiphtheriae* and *Coccidioidomyces laziensis*). Subjects received intranasal administration of 1 × 10^8 colony-forming units / 600 µL / day for three days, followed by a 14-day washout period. In additional assays, a similar protocol was followed, with the addition of chemotherapy to screen for combined treatment efficacy.
[0148] Computed tomography imaging. The single-segment SOMATOM Definition AS 64-slice spiral CT scanner (Siemens Healthcare Ltd, Camberley, UK) is used for all advanced imaging procedures.
[0149] Histopathology OPA tissues were fixed in 4% formaldehyde (Genta Medical, UK) for at least 24 hours (depending on tissue thickness), then processed using the Thermo Fisher Scientific Excelsior AS tissue processor (Thermo Fisher Scientific, UK) and embedded in paraffin. Tissue sections were prepared using a Leica RM2235 rotary microtome (Leica Microsystems Ltd, UK); 4 μm sections were placed on SuperFrost Plus slides (Thermo Fisher Scientific, UK) and dried at 53°C for at least 4 hours.
[0150] For hematoxylin and eosin staining, slides were deparaffinized in 100% xylene by three alternations for 5 minutes each, followed by rehydration in alcohol; then by two alternations in 100% ethanol, followed by 80% and then 50%, each for 2 minutes. Slides were washed in running water for 2 minutes, then placed in hematoxylin (Shandong Harris Hematoxylin, Thermo Fisher Scientific, UK) for up to 10 minutes. Slides were washed in running water for 2 minutes, then placed in Scott's tap water substitute for up to 10 minutes, until the tissue sections turned blue. Counterstaining was performed by placing the slides in eosin Y (Shandong Eosin Y Cytoplasmic Counterstain, Thermo Fisher Scientific, UK) for 5 minutes. Dehydration was performed by placing the slides in alcohol; 50% ethanol for 30 seconds, 80% ethanol for 30 seconds, then two alternations in 100% ethanol for 2 minutes each. Place the slide in xylene for 10 minutes, then seal it with a coverslip using DXP sealing agent (Sigma-Aldrich, UK).
[0151] Example 14: Corynebacterium spp. growth test The following steps were performed to determine the growth rate properties of *Corynebacterium pseudodiphtheriae* strains. *Corynebacterium pseudodiphtheriae* colonies were inoculated into 9 mL of 1% Colombian Tween broth and incubated overnight at 37°C with shaking at 200 rpm. OD600 was measured on the overnight culture, and 30 mL of fresh 1% Colombian Tween broth was inoculated to achieve an initial OD600 of 0.04. The culture was then incubated at 37°C with shaking at 200 rpm. OD600 measurements were performed over a 14.5-hour period. The results of OD600 measurements for ATCC 10700 growth are shown in... Figure 2A In the middle, and Figure 2BThe Y-axis is shown as Log(OD600). As can be seen, the doubling time for the logarithmic phase (2 to 6 hours) is approximately 86 minutes. The results of OD600 measurements for JCM 1320 growth are shown in... Figure 3A In the middle, and Figure 3B The Y-axis is shown as Log(OD600). As can be seen, the doubling time for the logarithmic period (2 to 6 hours) is approximately 129 minutes.
[0152] To determine co-culture growth, the starting inoculum was modified to achieve a mixed culture while maintaining an initial OD600 of 0.04. For example, for a 75% JCM 1320 / 25% ATCC 10700 mixture, diluting the overnight culture to 0.04 with 400 μL required 300 μL of JCM 1320 culture and 100 μL of ATCC 10700 culture. OD600 measurements were performed over a 14.5-hour period. The results of the OD600 measurements during growth are shown in... Figure 4A Among them, samples A, B, C, D, and E are 100% ATCC 10700, 25% JCM 1320, 75% ATCC 10700, 50% JCM 1320, 75% JCM 1320, 25% ATCC 10700, and 100% JCM 1320, respectively. The results of the Log(OD600) measurement of growth are shown in... Figure 4B In, among which Figure 4A The samples were ordered sequentially, showing the same data trend line. Doubling times were as follows: 100% ATCC 10700 [86 min], 25% JCM 1320 and 75% ATCC 10700 [89 min], 50% JCM 1320 and 50% ATCC 10700 [91 min], 75% JCM 1320 and 25% ATCC 10700 [98 min], and 100% JCM 1320 [129 min]. Doubling times appeared to be primarily driven by the ATCC 10700 strain. The final stationary phase cell density of the mixed cultures was within a similar range (OD). 600 ± 0.1).
[0153] Example 15: Polymer Growth Test The following steps were performed to determine the co-culture properties of *Corynebacterium pseudodiphtheriae* strains. First, direct co-culture of *Corynebacterium pseudodiphtheriae* strains ATCC 10700 and JCM 1320 was conducted. Two very similar *Corynebacterium pseudodiphtheriae* strains were simultaneously spotted on Columbia 1% Tween agar plates: four ATCC 10700 spots on the upper left and four JCM 1320 spots on the upper right. Images were taken 24 hours after spotting, as shown below. Figure 5 As shown. Figure 5 As can be seen, the cultures do not show antagonistic characteristics between different strains. This is an unexpected result, as co-culture of clinical isolates of Corynebacterium pseudodiphtheriae has not been reported to date.
[0154] Second, perform direct co-culture of *Corynebacterium pseudodiphtheriae* strains ATCC 10700 or JCM 1320 and *Coccidia laziensis*. Images are taken 24 hours after sample application, such as... Figure 6 As shown. Reference Figure 6 The left side of the image shows a column after two spottings with ATCC 10700, and the right side shows a column after two spottings with *Coccus laziensis*. The right side of the image shows a column after two spottings with *Coccus laziensis*, and the right side shows a column after two spottings with JCM 1320. (The last sentence appears to be incomplete and possibly refers to a different image.) Figure 6 As can be seen, the cultures do not show antagonistic characteristics between different strains.
[0155] Although some embodiments of the invention have been shown and described herein, it will be apparent to those skilled in the art that such embodiments are provided by way of example only. Many variations, modifications, and substitutions will now be apparent to those skilled in the art without departing from the invention. It should be understood that various alternatives to the embodiments of the invention described herein can be used to practice the invention. The appended claims are intended to define the scope of the invention and thereby cover the methods and structures within the scope of these claims and their equivalents.
[0156] This application provides the following: 1. A pharmaceutical composition, wherein the pharmaceutical composition comprises: A live, purified bacterial population, wherein the live, purified bacterial population includes various Corynebacterium pseudodiphtheriae ( ). Corynebacterium pseudodiphtheriticum ) strains; and Pharmaceutically acceptable excipients.
[0157] 2. A pharmaceutical composition, wherein the pharmaceutical composition comprises: A live, purified bacterial population, wherein the live, purified bacterial population includes various corynebacteria; and Pharmaceutically acceptable excipients.
[0158] 3. A pharmaceutical composition, wherein the pharmaceutical composition comprises: A live, purified bacterial population, wherein the live, purified bacterial population includes: Various lazy and cunning cocci ( Dolosigranulum pigrum ) strains; and Pharmaceutically acceptable excipients.
[0159] 4. A pharmaceutical composition, wherein the pharmaceutical composition comprises: A live, purified bacterial population, wherein the live, purified bacterial population includes: Multiple strains of Corynebacterium pseudodiphtheriae; and At least one strain of *Lazy Cunning Cocci*; and Pharmaceutically acceptable excipients.
[0160] 5. A pharmaceutical composition, wherein the pharmaceutical composition comprises: A live, purified bacterial population, said live, purified bacterial population being present in a total amount of at least 10^3 cfu, and said live, purified bacterial population comprising: At least one strain of Corynebacterium pseudodiphtheriae; and At least one strain of *Lazy Cunning Cocci*; and Pharmaceutically acceptable excipients, wherein the pharmaceutical composition is formulated for intranasal administration.
[0161] 6. A pharmaceutical composition, wherein the pharmaceutical composition comprises: A live, purified bacterial population, said live, purified bacterial population being present in a total amount of at least 10^3 cfu, and said live, purified bacterial population comprising: At least one strain of Corynebacterium pseudodiphtheriae; and At least one strain of *Lazy Cunning Cocci*; and Pharmaceutically acceptable excipients, wherein the pharmaceutical composition is formulated for oral administration.
[0162] 7. The pharmaceutical composition according to any one of items 1 to 4, wherein the pharmaceutical composition is formulated for intranasal administration.
[0163] 8. The pharmaceutical composition according to any one of items 1 to 4, wherein the pharmaceutical composition is formulated for oral administration.
[0164] 9. The pharmaceutical composition according to any one of items 1 to 4, wherein the pharmaceutical composition is in the form of a liquid, solid, semi-solid or aerosol dosage form.
[0165] 10. The pharmaceutical composition according to any one of items 1 to 4, wherein the pharmaceutical composition is in the dosage form of a suspension, capsule, gel, tablet, lozenge, pill or powder.
[0166] 11. The pharmaceutical composition according to any one of items 1 to 4 and 7, wherein the live, purified bacterial population is lyophilized.
[0167] 12. The pharmaceutical composition according to item 1, wherein the plurality of Corynebacterium pseudodiphtheriae strains include the plurality of strains listed in Table 1.
[0168] 13. The pharmaceutical composition according to item 1, wherein the plurality of Corynebacterium pseudodiphtheriae strains include JCM1320 or ATCC 10700.
[0169] 14. The pharmaceutical composition according to item 1, wherein the plurality of Corynebacterium pseudodiphtheriae strains include JCM1320 and ATCC 10700.
[0170] 15. The pharmaceutical composition according to item 14, wherein the live, purified bacterial population is lyophilized.
[0171] 16. The pharmaceutical composition according to item 1, wherein the live, purified bacterial population is present in a total amount of at least 10^3 cfu.
[0172] 17. The pharmaceutical composition according to any one of items 1 to 15, wherein the pharmaceutical composition is in a nasal spray bottle.
[0173] 18. The pharmaceutical composition according to any one of items 1 to 17, wherein the live, purified bacterial population is present in a total amount of up to 10^15 cfu.
[0174] 19. The pharmaceutical composition according to any one of items 1 to 4 and 7 to 12, wherein the live, purified bacterial population is present in a total amount of at least 10^3 cfu.
[0175] 20. The pharmaceutical composition according to any one of items 1 to 12, wherein the live, purified bacterial population is present in a total amount of 10^3 cfu to 10^12 cfu.
[0176] 21. The pharmaceutical composition according to item 2, wherein the plurality of corynebacteria includes *Corynebacterium clausti* (…). C. accolens Corynebacterium pseudodiphtheriae, Corynebacterium amylopectinum ( C. amycolatum ), Corynebacterium propionate ( C. propinquum ), Corynebacterium glutamicum ( C. glutamicum ) or Corynebacterium bandingense (C. striatum ).
[0177] 22. The pharmaceutical composition according to item 2, wherein the plurality of corynebacteria includes species selected from the strains listed in Table 1.
[0178] 23. The pharmaceutical composition according to any one of items 1 and 4 to 6, wherein the pseudocorynebacterium is selected from the strains listed in Table 1.
[0179] 24. The pharmaceutical composition according to any one of items 3 to 6, wherein the *Lazy Coccidia* is selected from the strains listed in Table 2.
[0180] 25. The pharmaceutical composition according to any one of items 1 to 24, wherein the live, purified bacterial community comprises up to 10 strains, optionally wherein the live, purified bacterial community comprises a mixture listed in Tables 4 to 7.
[0181] 26. A method comprising administering a pharmaceutical composition according to any one of items 1 to 25 to a subject in need, wherein the subject suffers from respiratory symptoms.
[0182] 27. The method according to Item 26, wherein the respiratory symptoms are MRSA, MSSA, asthma, COPD, rhinitis, lung cancer, pneumonia (optionally, hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), or community-acquired pneumonia (CAP)), cystic fibrosis, idiopathic pulmonary fibrosis, or interstitial lung disease.
[0183] 28. Use of a pharmaceutical composition according to any one of items 1 to 25 in the manufacture of a medicament for treating a subject with MRSA, MSSA, asthma, COPD, rhinitis, lung cancer, pneumonia (optionally, hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), or community-acquired pneumonia (CAP)), cystic fibrosis, idiopathic pulmonary fibrosis, or interstitial lung disease.
[0184] 29. A method for microbiome modification in a subject, the method comprising: Administer to subjects in need: a purified, live bacterial population comprising at least one bacterial strain present in an amount sufficient to prevent or treat lung symptoms, wherein the at least one bacterial strain is isolated from the upper respiratory tract of a donor, and optionally wherein the live, purified bacterial population comprises a mixture listed in Tables 4 to 7.
[0185] 30. A method for treating inflammatory lung symptoms, the method comprising: Administer to a subject with symptoms of inflammatory lung disease: a purified, live bacterial population comprising at least one bacterial strain present in an amount sufficient to reduce the incidence of pathogen colonization in the nasal cavity, wherein the at least one bacterial strain was isolated from the upper respiratory tract of a donor, and optionally wherein the purified, live bacterial population comprises a mixture listed in Tables 4 to 7.
[0186] 31. The method according to item 30, wherein the pathogenic bacteria include Staphylococcus aureus ( Staphylococcus aureusStreptococcus pneumoniae () Streptococcus pneumoniae ) or Pseudomonas aeruginosa ( Pseudomonas aeruginosa ).
[0187] 32. The method according to item 30, wherein the pathogen is a strain listed in Table 3.
[0188] 33. A method for treating lower respiratory tract symptoms, the method comprising: A live, purified bacterial population was administered intranasally to a subject suffering from a lower respiratory tract infection, wherein the live, purified bacterial population included: At least one strain of Corynebacterium pseudodiphtheriae; and At least one strain of Lazy Cunning Cocci.
[0189] 34. A method for reducing the colonization of pathogenic microorganisms in the anterior nasal cavity or nasal cavity of a subject, the method comprising the following steps: A live, purified bacterial population is administered to the subject who has pathogenic microorganisms in the subject's anterior nasal cavity or nasal cavity, wherein the live, purified bacterial population includes a variety of Corynebacterium pseudodiphtheriae strains.
[0190] 35. The method according to item 34, wherein the pathogenic microorganism includes Staphylococcus aureus, Streptococcus pneumoniae, or Pseudomonas aeruginosa.
[0191] 36. The method according to item 34, wherein the live, purified bacterial population comprises the mixtures listed in Tables 4 to 7.
[0192] 37. The method according to item 34, wherein the live, purified bacterial population comprises the mixtures listed in Tables 4 to 7.
[0193] 38. The method according to item 34, wherein the plurality of Corynebacterium pseudodiphtheriae strains include JCM 1320 or ATCC 10700.
[0194] 39. The method according to item 34, wherein the plurality of Corynebacterium pseudodiphtheriae strains include JCM 1320 and ATCC 10700.
[0195] 40. The method according to item 34, wherein the plurality of Corynebacterium pseudodiphtheriae strains include strains selected from those listed in Table 1.
[0196] 41. A method for reducing the colonization of pathogenic microorganisms in the anterior nasal cavity or nasal cavity of a subject, the method comprising the steps of: A live, purified bacterial population, comprising a variety of Corynebacterium species, is administered to the subject who has pathogenic microorganisms in the subject's anterior nostril or nasal cavity.
[0197] 42. The method according to item 41, wherein the plurality of rod-shaped bacteria includes *Corynebacterium bulgaricum*, *Corynebacterium pseudodiphtheriae*, *Corynebacterium amylopectinum*, *Corynebacterium propionate*, *Corynebacterium glutamicum*, or *Corynebacterium bandingense*.
[0198] 43. The method according to item 41, wherein the pathogenic microorganism includes Staphylococcus aureus, Streptococcus pneumoniae, or Pseudomonas aeruginosa.
[0199] 44. A method for restoring the sense of smell, the method comprising: A live, purified bacterial population, comprising a variety of Corynebacterium species, was administered to subjects with symptoms of airway inflammation.
[0200] 45. A method for treating inflammatory symptoms of the airways, the method comprising: A live, purified bacterial population, comprising a variety of Corynebacterium species, was administered to subjects with symptoms of airway inflammation.
[0201] 46. A method for treating inflammatory symptoms of the airways, the method comprising: Live, purified bacterial populations were administered to subjects with airway inflammatory symptoms, wherein the live, purified bacterial populations included multiple strains of *Lola nigra*.
[0202] 47. A method for treating inflammatory symptoms of the airways, the method comprising: Administering live, purified bacterial populations to subjects in need, wherein the live, purified bacterial populations include: multiple strains of Corynebacterium pseudodiphtheriae; and at least one strain of Coccidia laziensis.
[0203] 48. The method according to any one of items 28 to 35, wherein the airway inflammatory condition is asthma, COPD, rhinitis, MRSA, MSSA, pneumonia (optionally, hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), or community-acquired pneumonia (CAP)), cystic fibrosis, idiopathic pulmonary fibrosis, or interstitial lung disease.
[0204] 49. A method for treating lung cancer, the method comprising: A live, purified bacterial population was administered to a subject with lung cancer, wherein the live, purified bacterial population included: At least one Corynebacterium, optionally at least one strain of Corynebacterium pseudodiphtheriae; and Optionally, at least one strain of Lazy Cunningcoccus.
[0205] 50. A method for treating cancer, the method comprising: Administering live, purified bacterial cultures as adjunctive therapy to subjects with cancer, wherein the live, purified bacterial cultures include: At least one Corynebacterium, optionally at least one strain of Corynebacterium pseudodiphtheriae; and Optionally, at least one strain of Lazy Cunningcoccus.
[0206] 51. The method according to item 50, wherein the adjunctive therapy is chemotherapy, radiation therapy, or checkpoint inhibitor therapy.
[0207] 52. The method according to item 51, wherein the live, purified bacterial population is applied before or after the application of the chemotherapy, the radiation therapy, or the checkpoint inhibitor therapy.
[0208] 53. The method according to item 50, wherein the cancer is a solid cancer or a hematopoietic system cancer.
[0209] 54. The method described in Item 53, wherein the solid cancer is carcinoma or sarcoma.
[0210] 55. The method described in Item 53, wherein the hematopoietic system cancer is leukemia, myeloma, or lymphoma.
[0211] 56. A method for treating asthma, the method comprising: A live, purified bacterial population was administered to a subject suffering from asthma, wherein the live, purified bacterial population included: At least one Corynebacterium, optionally at least one strain of Corynebacterium pseudodiphtheriae; and Optionally, at least one strain of Lazy Cunningcoccus.
[0212] 57. A method for treating symptoms of viral infection, the method comprising: Administering live, purified bacterial cultures to subjects suffering from viral infection symptoms, wherein the live, purified bacterial cultures include: At least one Corynebacterium, optionally at least one strain of Corynebacterium pseudodiphtheriae; and Optionally, at least one strain of Lazy Cunningcoccus.
[0213] 58. The method according to Item 57, wherein the viral infection is influenza A, influenza B, adenovirus, respiratory syncytial virus (RSV), enterovirus (EVs), human rhinovirus (HRV), human metapneumovirus (HMPV), human bocavirus (HBoV), coronavirus (CoV), or parainfluenza virus (PIV).
[0214] 59. A method for treating idiopathic pulmonary fibrosis, the method comprising: A live, purified bacterial population was administered to a subject with idiopathic pulmonary fibrosis, wherein the live, purified bacterial population included: At least one Corynebacterium, optionally at least one strain of Corynebacterium pseudodiphtheriae; and Optionally, at least one strain of Lazy Cunningcoccus.
[0215] 60. A method for treating COPD, the method comprising: A live, purified bacterial population was administered to a subject with COPD, wherein the live, purified bacterial population included: At least one Corynebacterium, optionally at least one strain of Corynebacterium pseudodiphtheriae; and Optionally, at least one strain of Lazy Cunningcoccus.
[0216] 61. A method for treating cystic fibrosis, the method comprising: A live, purified bacterial population was administered to a subject with cystic fibrosis, wherein the live, purified bacterial population included: At least one Corynebacterium, optionally at least one strain of Corynebacterium pseudodiphtheriae; and Optionally, at least one strain of Lazy Cunningcoccus.
[0217] 62. A method for treating MRSA, the method comprising: A purified bacterial population, present in a total amount of at least 10^3 cfu, was administered intranasally to a subject with MRSA, wherein the live, purified bacterial population comprised: At least one Corynebacterium, optionally at least one strain of Corynebacterium pseudodiphtheriae; and At least one strain of Lazy Cunning Cocci.
[0218] 63. A method for treating pneumonia, the method comprising: A live, purified bacterial population was administered intranasally to a subject suffering from pneumonia, the live, purified bacterial population being present in a total amount of at least 10^3 cfu, wherein the live, purified bacterial population comprised: At least one Corynebacterium, optionally at least one strain of Corynebacterium pseudodiphtheriae; and At least one strain of Lazy Cunning Cocci.
[0219] 64. The method according to any one of items 29 to 61, wherein the live, purified bacterial population is administered intranasally.
[0220] 65. The method according to any one of items 29 to 61, wherein the live, purified bacterial population is administered orally.
[0221] 66. The method according to any one of items 26 to 63, wherein the subject is an infant.
[0222] 67. The method according to any one of items 26 to 63, wherein the subject is a child.
[0223] 68. The method according to any one of items 26 to 63, wherein the subject is an adult.
[0224] 69. A kit, wherein the kit comprises: A first container, wherein the first container comprises a live, purified, and lyophilized bacterial population, the live, purified, and lyophilized bacterial population comprising: multiple strains of Corynebacterium pseudodiphtheriae; and A second container, wherein the second container comprises a pharmaceutically acceptable excipient.
[0225] 70. A kit, wherein the kit comprises: A first container, wherein the first container comprises a live, purified, and lyophilized bacterial population, the live, purified, and lyophilized bacterial population comprising: various Corynebacteria; and A second container, wherein the second container comprises a pharmaceutically acceptable excipient.
[0226] 71. A kit, wherein the kit comprises: A first container, wherein the first container comprises a live, purified, and lyophilized bacterial population, the live, purified, and lyophilized bacterial population comprising: multiple strains of *Coccidia laziensis*; and A second container, wherein the second container comprises a pharmaceutically acceptable excipient.
[0227] 72. A kit, wherein the kit comprises: A first container, wherein the first container comprises a live, purified, and lyophilized bacterial population, the live, purified, and lyophilized bacterial population comprising: Multiple strains of Corynebacterium pseudodiphtheriae; and Multiple strains of lazy and deceitful cocci and; and A second container, wherein the second container comprises a pharmaceutically acceptable excipient.
[0228] 73. A kit, wherein the kit comprises: A first container, wherein the first container comprises a live, purified, and lyophilized bacterial population present in a total amount of at least 10^3 cfu, the live, purified, and lyophilized bacterial population comprising: Corynebacterium pseudodiphtheriae strains; and Lazy and Deceitful Cocci strains; and A second container, wherein the second container comprises a pharmaceutically acceptable excipient.
[0229] 74. The kit according to any one of items 69 to 73, wherein the live, purified and lyophilized bacterial population is present in a total amount of up to 10^15 cfu.
[0230] 75. The kit according to any one of items 69 to 73, wherein the live, purified and lyophilized bacterial population is present in a total amount of 10^3 cfu to 10^12 cfu.
[0231] 76. Use of a pharmaceutical composition according to any one of items 1 to 25 in the manufacture of a medicament for treating Parkinson's disease (PD), incidental Lewybody disorder (iLBD), dementia with Lewy bodies (DLB), Alzheimer's disease (AD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP), frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), pure autonomic failure (PAF), schizophrenia or Creutzfeldt-Jakob disease (CJD), autism spectrum disorder (ASD), post-traumatic stress disorder (PTSD), anxiety disorder, or depression.
[0232] 77. A method for treating neurological symptoms, the method comprising: Administered to subjects with neurological symptoms: a purified, live bacterial population comprising at least one bacterial strain present in an amount sufficient to reduce the incidence of pathogen colonization in the nasal cavity, wherein the at least one bacterial strain was isolated from the upper respiratory tract of a donor.
[0233] 78. The method according to item 77, wherein the pathogenic bacteria include Staphylococcus aureus, Streptococcus pneumoniae, Pseudomonas aeruginosa, or Burkholderia pseudomallei (…). Burkholderia pseudomallei ).
[0234] 79. The method according to item 78, wherein the pathogen is a strain listed in Table 3.
[0235] 80. A method for microbiome modification in a subject, the method comprising: Intranasal administration to a subject in need: a purified, live bacterial population comprising at least one bacterial strain present in an amount sufficient to treat neurological symptoms, wherein the at least one bacterial strain was isolated from the upper respiratory tract of a donor.
[0236] 81. A method for treating neurological symptoms, the method comprising: A live, purified bacterial population was administered to a subject suffering from a nervous system infection, wherein the live, purified bacterial population included: At least one strain of Corynebacterium pseudodiphtheriae; and At least one strain of Lazy Cunning Cocci.
[0237] 82. A method for treating neurological symptoms, the method comprising: A live, purified bacterial population, comprising a variety of Corynebacterium species, was administered to a subject suffering from neurological symptoms.
[0238] 83. A method for treating neurological symptoms, the method comprising: Live, purified bacterial populations were administered to subjects with neurological symptoms, wherein the live, purified bacterial populations included multiple strains of *Lola cuneiformis*.
[0239] 84. A method for treating neurological symptoms, the method comprising: A live, purified bacterial population was administered to a subject with neurological symptoms, wherein the live, purified bacterial population included: multiple strains of Corynebacterium pseudodiphtheriae; and at least one strain of Coccidia laziensis.
[0240] 85. The method according to any one of items 66 to 73, wherein the neurological condition is Parkinson's disease (PD), iLY body syndrome (iLBD), Lewy body dementia (DLB), Alzheimer's disease (AD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP), frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), pure autonomic failure (PAF), schizophrenia, Creutzfeldt-Jakob disease (CJD), autism spectrum disorder (ASD), post-traumatic stress disorder (PTSD), anxiety disorder, or depression.
[0241] 86. The method according to any one of items 77 to 85, wherein the subject suffers from olfactory perception deficit.
[0242] 87. A method for treating Parkinson's disease, the method comprising: Administering live, purified bacterial cultures to subjects with Parkinson's disease, wherein the live, purified bacterial cultures include: At least one Corynebacterium, optionally at least one strain of Corynebacterium pseudodiphtheriae; and Optionally, at least one strain of Lazy Cunningcoccus.
[0243] 88. A method for treating occasional Lewy body symptoms, the method comprising: A live, purified bacterial population was administered to a subject suffering from occasional Lewy body syndrome, wherein the live, purified bacterial population included: At least one Corynebacterium, optionally at least one strain of Corynebacterium pseudodiphtheriae; and Optionally, at least one strain of Lazy Cunningcoccus.
[0244] 89. A method for treating Lewy body dementia, the method comprising: A live, purified bacterial population was administered to subjects with Lewy body dementia, wherein the live, purified bacterial population included: At least one Corynebacterium, optionally at least one strain of Corynebacterium pseudodiphtheriae; and Optionally, at least one strain of Lazy Cunningcoccus.
[0245] 90. A method for treating Alzheimer's disease, the method comprising: A live, purified bacterial population was administered to a subject with Alzheimer's disease, wherein the live, purified bacterial population included: At least one Corynebacterium, optionally at least one strain of Corynebacterium pseudodiphtheriae; and Optionally, at least one strain of Lazy Cunningcoccus.
[0246] 91. A method for treating multiple system atrophy, the method comprising: A live, purified bacterial population was administered to a subject suffering from multiple system atrophy, wherein the live, purified bacterial population included: At least one Corynebacterium, optionally at least one strain of Corynebacterium pseudodiphtheriae; and Optionally, at least one strain of Lazy Cunningcoccus.
[0247] 92. A method for treating progressive supranuclear palsy, the method comprising: A live, purified bacterial population was administered to a subject suffering from progressive supranuclear palsy, wherein the live, purified bacterial population included: At least one Corynebacterium, optionally at least one strain of Corynebacterium pseudodiphtheriae; and Optionally, at least one strain of Lazy Cunningcoccus.
[0248] 93. A method for treating frontotemporal dementia, the method comprising: A live, purified bacterial population was administered to subjects with frontotemporal dementia, wherein the live, purified bacterial population included: At least one Corynebacterium, optionally at least one strain of Corynebacterium pseudodiphtheriae; and Optionally, at least one strain of Lazy Cunningcoccus.
[0249] 94. A method for treating amyotrophic lateral sclerosis (ALS), the method comprising: A live, purified bacterial population was administered to a subject suffering from amyotrophic lateral sclerosis (ALS), wherein the live, purified bacterial population included: At least one Corynebacterium, optionally at least one strain of Corynebacterium pseudodiphtheriae; and Optionally, at least one strain of Lazy Cunningcoccus.
[0250] 95. A method for treating pure autonomic nervous system failure, the method comprising: A live, purified bacterial population was administered to subjects suffering from pure autonomic nervous system failure, wherein the live, purified bacterial population included: At least one Corynebacterium, optionally at least one strain of Corynebacterium pseudodiphtheriae; and Optionally, at least one strain of Lazy Cunningcoccus.
[0251] 96. A method for treating schizophrenia, the method comprising: A live, purified bacterial population was administered to a subject suffering from schizophrenia, wherein the live, purified bacterial population included: At least one Corynebacterium, optionally at least one strain of Corynebacterium pseudodiphtheriae; and Optionally, at least one strain of Lazy Cunningcoccus.
[0252] 97. A method for treating Creutzfeldt-Jakob disease (CJD), the method comprising: A live, purified bacterial population was administered to a subject with Creutzfeldt-Jakob disease, wherein the live, purified bacterial population included: At least one Corynebacterium, optionally at least one strain of Corynebacterium pseudodiphtheriae; and Optionally, at least one strain of Lazy Cunningcoccus.
[0253] 98. A method for treating autism spectrum disorder (ASD), the method comprising: A live, purified bacterial population was administered to a subject with ASD, wherein the live, purified bacterial population included: At least one Corynebacterium, optionally at least one strain of Corynebacterium pseudodiphtheriae; and Optionally, at least one strain of Lazy Cunningcoccus.
[0254] 99. A method for treating post-traumatic stress disorder (PTSD), the method comprising: Administering live, purified bacterial cultures to subjects suffering from PTSD, wherein the live, purified bacterial cultures include: At least one Corynebacterium, optionally at least one strain of Corynebacterium pseudodiphtheriae; and Optionally, at least one strain of Lazy Cunningcoccus.
[0255] 100. A method for treating anxiety disorder, the method comprising: A live, purified bacterial population was administered to subjects suffering from anxiety disorders, wherein the live, purified bacterial population included: At least one Corynebacterium, optionally at least one strain of Corynebacterium pseudodiphtheriae; and Optionally, at least one strain of Lazy Cunningcoccus.
[0256] 101. A method for treating depression, the method comprising: A live, purified bacterial population was administered to a subject suffering from depression, wherein the live, purified bacterial population included: At least one Corynebacterium, optionally at least one strain of Corynebacterium pseudodiphtheriae; and Optionally, at least one strain of Lazy Cunningcoccus.
[0257] 102. The method according to any one of items 81 to 101, wherein the live, purified bacterial population is administered intranasally.
[0258] 103. The method according to any one of items 81 to 101, wherein the live, purified bacterial population is administered orally.
[0259] 104. The method according to any one of items 77 to 101, wherein the subject is an infant.
[0260] 105. The method according to any one of items 77 to 101, wherein the subject is a child.
[0261] 106. The method according to any one of items 77 to 101, wherein the subject is an adult.
[0262] 107. The method according to item 106, wherein the adult is 65 years of age or older.
[0263] 108. The method according to any one of items 41 to 45, 49 to 68, 82, 87 to 101, wherein the genus Corynebacterium includes 1, 2, 3, 4, 5 or more species listed in Table 1.
[0264] 109. The method according to any one of items 41 to 45, 49 to 68, 82, 87 to 101, wherein the genus Corynebacterium includes strains 1, 2, 3, 4, 5 or more listed in Table 1.
[0265] 110. The method according to any one of items 33 to 40, 47 to 68, 81 and 84 to 101, wherein the pseudocorynebacterium includes JCM 1320 and / or ATCC 10700.
Claims
1. Use of live, purified bacterial populations in the preparation of medicaments for reducing the colonization of pathogenic microorganisms in the anterior nasal cavity or nasal cavity of a subject. The live, purified bacterial population is administered to the subject who has pathogenic microorganisms in the nostrils or nasal cavity of the subject, and the live, purified bacterial population includes: Various lazy and cunning cocci ( Dolosigranulum pigrum ) strains, wherein the various lazy and deceitful cocci strains provide multiple bactericidal mechanisms; and At least one Corynebacterium pseudodiphtheriae ( Corynebacterium pseudodiphtheriticum ) strain.
2. The use according to claim 1, wherein the plurality of Lazy Coccidia strains include strains 1, 2, 3, 4, 5 or more listed in Table 2.
3. The use according to claim 1, wherein the plurality of Lazy Coccidia strains comprises at least three Lazy Coccidia strains.
4. The use according to claim 1, wherein the plurality of *Lola dell'assima* strains include four *Lola dell'assima* strains.
5. The use according to claim 1, wherein the pathogenic microorganism includes Staphylococcus aureus (… Staphylococcus aureus Streptococcus pneumoniae () Streptococcus pneumoniae ) or Pseudomonas aeruginosa ( Pseudomonas aeruginosa ).
6. The use according to claim 1, wherein the at least one Corynebacterium pseudodiphtheriae strain comprises JCM 1320 or ATCC 10700.
7. The use according to claim 1, wherein the live, purified bacterial community is in a nasal spray bottle.
8. The use according to claim 1, wherein the live, purified bacterial population is present in a total amount of at least 10^3 cfu.
9. The use according to claim 1, wherein the live, purified bacterial population is present in a total amount of up to 10^15 cfu.
10. The use according to claim 1, wherein the live, purified bacterial population is present in a total amount of 10^3 cfu to 10^12 cfu.
11. The use according to claim 1, wherein the live, purified bacterial population is in the form of a gel.
12. The use according to claim 1, wherein the live, purified bacterial population is in liquid form.
13. Use of live, purified bacterial populations in the preparation of medicaments for reducing the colonization of pathogenic microorganisms in the anterior nasal cavity or nasal cavity of a subject. The live, purified bacterial population is administered to the subject who has pathogenic microorganisms in the nostrils or nasal cavity of the subject, and the live, purified bacterial population includes: Various lazy and cunning cocci ( Dolosigranulum pigrum ) strain; and At least one type of rod-shaped bacterium ( Corynebacterium ) strain.
14. The use according to claim 13, wherein the plurality of *Lazy Coccidia* strains include strains 1, 2, 3, 4, 5 or more listed in Table 2.
15. The use according to claim 13, wherein the plurality of *Lola dell'assima* strains comprises at least three *Lola dell'assima* strains.
16. The use according to claim 13, wherein the plurality of *Lola dell'ovarian* strains comprises four *Lola dell'ovarian* strains.
17. The use according to claim 13, wherein the plurality of Lazy Cunning Cocci strains provide a plurality of bactericidal mechanisms.
18. The use according to claim 13, wherein the pathogenic microorganism comprises Staphylococcus aureus ( Staphylococcus aureus Streptococcus pneumoniae () Streptococcus pneumoniae ) or Pseudomonas aeruginosa ( Pseudomonas aeruginosa ).
19. The use according to claim 13, wherein the at least one Corynebacterium strain comprises *Corynebacterium bulgaricum* (…). C. accolens ), Corynebacterium amylopectin ( C. amycolatum ), Corynebacterium propionate ( C. propinquum ), Corynebacterium glutamicum ( C. glutamicum ) or Corynebacterium bandingense ( C. striatum At least one strain of the species.
20. The use according to claim 13, wherein the live, purified bacterial community is in a nasal spray bottle.
21. The use according to claim 13, wherein the live, purified bacterial population is present in a total amount of at least 10^3 cfu.
22. The use according to claim 13, wherein the live, purified bacterial population is present in a total amount of up to 10^15 cfu.
23. The use according to claim 13, wherein the live, purified bacterial population is present in a total amount of 10^3 cfu to 10^12 cfu.
24. The use according to claim 13, wherein the live, purified bacterial population is in the form of a gel.
25. The use according to claim 13, wherein the live, purified bacterial population is in liquid form.
26. A pharmaceutical composition, wherein the pharmaceutical composition comprises: A live, purified bacterial population, wherein the live, purified bacterial population includes various Corynebacterium pseudodiphtheriae ( Corynebacterium pseudodiphtheriticum ) strains; and Pharmaceutically acceptable excipients.
27. A pharmaceutical composition, wherein the pharmaceutical composition comprises: A live, purified bacterial community, wherein the live, purified bacterial community includes a variety of corynebacteria; as well as Pharmaceutically acceptable excipients.
28. A pharmaceutical composition, wherein the pharmaceutical composition comprises: A live, purified bacterial population, wherein the live, purified bacterial population includes: Various lazy and cunning cocci ( Dolosigranulum pigrum ) strains; and Pharmaceutically acceptable excipients.
29. A pharmaceutical composition, wherein the pharmaceutical composition comprises: A live, purified bacterial population, wherein the live, purified bacterial population includes: Multiple strains of Corynebacterium pseudodiphtheriae; and At least one strain of *Lazy Cunning Cocci*; and Pharmaceutically acceptable excipients.
30. A pharmaceutical composition, wherein the pharmaceutical composition comprises: A live, purified bacterial population, wherein the live, purified bacterial population is present in a total amount of at least 10^3 cfu, and wherein the live, purified bacterial population comprises: At least one strain of Corynebacterium pseudodiphtheriae; and At least one strain of *Lazy Cunning Cocci*; and Pharmaceutically acceptable excipients, wherein the pharmaceutical composition is formulated for intranasal administration.
31. A pharmaceutical composition, wherein the pharmaceutical composition comprises: A live, purified bacterial population, said live, purified bacterial population being present in a total amount of at least 10^3 cfu, and said live, purified bacterial population comprising: At least one strain of Corynebacterium pseudodiphtheriae; and At least one strain of *Lazy Cunning Cocci*; and Pharmaceutically acceptable excipients, wherein the pharmaceutical composition is formulated for oral administration.