Algolifer sp., Bosea sp., Bravendimonas sp., Desulfovibrio sp., Microbacterium sp., Sphingomonas sp., and Variovorax sp. for use in the prevention and treatment of diseases.

Abstract

Therapeutic compounds and their use in the prevention and treatment of disease are disclosed. The compounds include one or more materials selected from algal biomass / supernatants (including both algae and bacteria), bacterial biomass, and isolated and purified compounds, as well as specific active sites or structures on those compounds. Therapeutic compounds derived from bacteria that appear to selectively alter one or more TLR pathways and the use of such compounds in the prevention and treatment of disease in both animals and humans. The bacteria are selected from the group consisting of Algoriphagus sp., Bosea sp., Brevundimonas sp., Desulfovibrio sp., Microbacterium sp., Sphingomonas sp., and Variovorax sp. The disclosed compounds and methods of treatment find particular use in treating diseases in poultry, particularly in the prevention and treatment of coccidiosis.

Description

Technical Field

[0001] The disclosed concept of the present invention relates to the use of novel compounds in the treatment of various diseases in animals and humans by selectively altering the TLR signaling pathway. More specifically, the disclosed concept of the present invention relates to methods of using and treating therapeutic compounds comprising one or more materials selected from algal biomass / supernatant (containing both algae and bacteria), bacterial biomass, and isolated and purified compounds, as well as specific active sites or structures on those compounds. Animals and humans treated with the therapeutic compounds of the present invention have a reduced severity or complete disappearance of a particular disease compared to untreated animal or human subjects. The therapeutic compounds may be administered orally as part of a natural feed composition or in the form of capsules or tablets. The therapeutic compounds may also be administered intravenously. The disclosed concept of the present invention is particularly applicable in the poultry industry, but can also find application in other animals other than poultry. The disclosed inventive concept can also be beneficial to humans.

Background Art

[0002] The commercial livestock industry is under constant economic pressure to develop breeding methods that maximize the commercially valuable numbers in a flock or herd. One such industry facing a dramatic increase in demand is the poultry industry. Chicken meat competes with pork and is the most consumed meat in the world. World chicken production is expected to need to meet a demand increase of over 120% by 2050.

[0003] [[ID=​​​​Among the diseases known to afflict poultry flocks, the most common are intestinal diseases, including coccidiosis, a disease caused by the parasitic protozoan Coccidia. The annual economic losses attributable solely to coccidiosis are estimated to exceed $3 billion, and these costs are expected to increase for a variety of reasons.

[0005] Firstly, the prevention of coccidiosis today is primarily achieved through the use of vaccines. A single dose of the vaccine is given very early in the broiler's life, especially on the day of hatching. While this approach has shown some effectiveness, vaccines are known to suffer from variability in controlling the disease over time. Experiments have shown that combining vaccines with supplements such as probiotics may improve prognosis, but this method has its own challenges.

[0006] Secondly, the treatment of coccidiosis today is conventionally carried out using both costly antibiotics and ionophores. The use of antibiotics and ionophores is under global pressure for many reasons, including environmental issues associated with the emergence of antibiotic-resistant pathogens. Drug resistance to antibiotics, ionophores, and synthetic therapeutic compounds is increasing, mainly due to misuse, and as a result, the effectiveness of these treatments is significantly impaired. Relatively recently, the European Union banned the use of certain antibiotics in amounts below therapeutic levels for use as feed additives. No new drugs have been approved in these categories for many years. Synthetic therapeutic compounds and other chemicals are also known, but they are not as effective as conventional antibiotics.

[0007] Thirdly, since the drug must be incorporated into the feed for the entire lifespan of the animal to achieve sufficient efficacy, known treatments would still be considered unsatisfactory, even if they remain economical and effective. This requirement results in significant costs for feed during the growth period.

[0008] Therefore, there is a need to develop practical and cost-effective non-antibiotic-based treatments for pathogenic infections such as coccidiosis in poultry. [Overview of the project]

[0009] The disclosed compounds and therapeutic methods of the present invention relate to bacterial-based compounds for use in the prevention and treatment of a wide range of diseases, including coccidiosis in poultry. More specifically, the present invention relates to bacterial-derived compounds that selectively alter one or more TLR pathways in the prevention and treatment of diseases in both animals and humans, and to the use of such compounds. The bacteria are selected from the group consisting of Algolifera sp., Bosea sp., Brevundimonas sp., Desulfovibrio sp., Microbacterium sp., Sphingomonas sp., and Variovorax sp.

[0010] The disclosed inventive compounds are incorporated into conventional feeds for administration to animals such as poultry for the treatment of diseases. The use of the disclosed inventive compounds may also be used in the treatment of various human diseases. The combination of the disclosed inventive compounds and conventional feeds treats disease conditions by altering one or more TLR pathways. The disclosed inventive compounds are natural products and therefore have no adverse effects on the environment.

[0011] During the treatment period, the disclosed compounds of the present invention are administered to animals via poultry feed, in the form of tablets or capsules, in drinking water, or both, together with corn-soybean-based feed. The therapeutic compounds may also be administered intravenously. Studies based on the use of animal feed stocks containing specific variations of the disclosed compounds of the present invention have revealed improved health and disease prevention in animals. The data show that feeding chickens (specifically broiler chickens) with corn / soybean feed supplemented with biomass containing the compounds of the present invention improves disease resistance in healthy animals while providing improved treatment in diseased animals. While conventional corn and soybean feeds are referred to herein, it should be understood that the disclosed compounds are not limited to wheat, but can also be advantageously used in combination with other forms of conventional animal feed. The evidence supports the conclusion that the compounds of the present invention alter the modulation of various TLR pathways.

[0012] The disclosed concept of the present invention has numerous advantageous uses in humans and animals, including, but not limited to, (1) preventing animal diseases, particularly coccidiosis in poultry; (2) providing treatment for diseased animals, particularly poultry suffering from coccidiosis; and (3) providing both disease prevention and disease treatment, all with natural compounds.

[0013] To fully understand the present invention, please refer to the attached diagrams. As shown in the diagrams, the notation "No Tx, No Challenge" means a study in which no treatment was administered to target animals that were not intentionally infected with coccidiosis. The notation "No Tx, Cocci" means a study in which no treatment was administered to target animals that were intentionally infected with coccidiosis. The notation "Anti-cocci, Cocci" means a study in which the target animals were infected with coccidiosis and administered an anticoccidial agent.

[0014] The designation "ZIVO VP-UG" refers to the first test in which a composition containing algal biomass-derived components, including V. paradoxus, was administered to the target animals. The designation "ZIVO VP-BS" refers to the second test in which a composition containing algal biomass-derived components, including V. paradoxus, was administered to the target animals. The designation "ZIVO Sym-VP" refers to the test in which a composition containing algal biomass-derived components, including Variovorax sp., Brevandimonas sp., Sphingomonas sp., and Microbacterium sp., was administered to the target animals. The designation "ZIVO Sym" refers to the test in which a composition containing algal biomass-derived components, including Brevandimonas sp., Sphingomonas sp., and Microbacterium sp., was administered to the target animals.

[0015] The attached diagram is explained as follows: [Brief explanation of the drawing]

[0016] [Figure 1] Figure 1 is a graph showing the feed conversion rate data for the experimental subjects from day 1 to day 28;

[0017] [Figure 2] Figure 2 is a graph showing the feed conversion rate data for the experimental subjects from day 1 to day 21;

[0018] [Figure 3] Figure 3 is a graph showing the feed conversion rate data for the experimental subjects from day 1 to day 14;

[0019] [Figure 4] Figure 4 is a graph showing the feed conversion rate data for the experimental subjects from day 15 to day 21;

[0020] [Figure 5]Figure 5 is a graph showing the feed conversion rate data of the experimental subjects from the 22nd day to the 28th day;

[0021] [Figure 6] Figure 6 is a graph showing the mortality rate of the experimental subjects from the 1st day to the 28th day;

[0022] [Figure 7] Figure 7 is a graph showing the mortality rate of the experimental subjects from the 1st day to the 21st day;

[0023] [Figure 8] Figure 8 is a graph showing the mortality rate of the experimental subjects from the 1st day to the 14th day;

[0024] [Figure 9] Figure 9 is a graph showing the mortality rate of the experimental subjects from the 15th day to the 21st day;

[0025] [Figure 10] Figure 10 is a graph showing the mortality rate of the experimental subjects from the​​​​​​​​​​​​​​​​​​​ [Figure 15] Figure 15 is a graph showing the average weight of the experimental subjects in grams from day 1 to day 14;

[0031] [Figure 16] Figure 16 is a graph showing the average weight gain in grams for the experimental subjects from day 1 to day 21;

[0032] [Figure 17] Figure 17 is a graph showing the average weight of the experimental subjects in grams from day 1 to day 28;

[0033] [Figure 18] Figure 18 is a graph showing the average weight of the experimental subjects in grams from day 1 to day 14 (additional test);

[0034] [Figure 19] Figure 19 is a graph showing the average weight of the experimental subjects in grams from day 15 to day 21 (additional test);

[0035] [Figure 20] Figure 20 is a graph showing the average weight of the subjects in grams from day 22 to day 28 (additional test);

[0036] [Figure 21] Figure 21 is a graph showing the feed intake of the experimental subjects from day 1 to day 14;

[0037] [Figure 22] Figure 22 is a graph showing the feed intake of the experimental subjects from day 1 to day 21;

[0038] [Figure 23] Figure 23 is a graph showing the feed intake of the experimental subjects from day 1 to day 28;

[0039] [Figure 24] Figure 24 is a graph showing the feed intake of the experimental subjects from day 15 to day 21; and,

[0040] [Figure 25] Figure 25 is a graph showing the feed intake of the experimental subjects from day 22 to day 28. [Modes for carrying out the invention]

[0041] The following description details various operating parameters and components for various configured embodiments. These specific parameters and components are included as examples and are not intended to be limiting. Unless otherwise noted, all technical and scientific terms used herein have the general meanings that would be understood by those skilled in the art.

[0042] The disclosed inventive concept method proposes the use of compounds in the prevention and treatment of diseases in both animals and humans. The therapeutic compounds comprise one or more materials selected from algal biomass / supernatant (containing both algae and bacteria), symbiotic bacteria, bacterial biomass, bacterial ferments, and isolated and purified compounds, as well as specific active sites or structures on those compounds. The compounds of the present invention are combined with conventional feeds to create mixed feeds which are given to chickens, such as broiler chickens and other animals to prevent diseases in healthy animals and treat diseases in sick animals.

[0043] Compounds used in growth promotion methods and treatments

[0044] The disclosed growth-promoting methods and treatments utilize effective disease-preventive and therapeutic compounds comprising algal biomass / supernatant (containing both algae and bacteria), bacterial biomass, and isolated and purified compounds, as well as one or more materials selected from specific active sites or structures on those compounds. Treatment can be achieved by administering these compounds to diseased animals. The effective compounds may be derived from the lipopolysaccharide (LPS) layer of Gram-negative bacteria, or from sources other than lipopolysaccharides.

[0045] In this specification, the terms “alteration” or “alter” refer to the effect of a molecule on altering the activity induced by another molecule. For example, compounds that may inhibit the LPS-dependent modulation of TLR receptors (including, but not limited to, TLR2, TLR3, TLR4, TLR6, TLR7, TLR8, and / or TLR9 receptors) present on the surface of human or animal immune cells are considered to alter this particular pathway.

[0046] In this specification, the term "bacterial culture" is defined as one or more bacterial organisms growing individually or together in a liquid culture medium. Unless otherwise expressly stated, the term "bacterial biomass" refers to bacterial cells (after the liquid culture medium has been removed). "Bacterial biomass" may be wet or dry.

[0047] Unless explicitly stated otherwise, the term “bacterial supernatant” is defined as the culture medium in which bacterial biomass is growing, containing compounds excreted from the bacterial biomass. Bacterial supernatant is obtained by growing bacterial biomass in a culture medium for an appropriate period of time, and then removing the bacterial cells by filtration and / or centrifugation.

[0048] The embodiments of the growth-promoting methods and therapeutic compounds described herein include one or more LPS / lipid A compounds produced by Gram-negative bacterial strains for use in altering one or more TLR signaling pathways. The bacterial strains include one or more of the following: Algolifera sp., Bosea sp., Bravendimonas sp., Desulfovibrio sp., Microbacterium sp., Sphingomonas sp., and Variovorax sp. Specific species of these bacteria include one or more of the following: Algoriphaqus aquaticus, Algoriphagus aquatilis, Bosea nasdae, Brevundimonas diminut, Brevundimonas vesicularis, Microbacterium testaceum, and Variovorax paradoxus.

[0049] Algolifegus is a genus of Gram-negative, non-spore-forming, non-motile bacteria found in freshwater lake biofilms.

[0050] Bosea is a genus of bacteria belonging to the family Rhizobiaceae, which comprises 10 genera, including plant-associated bacteria such as the genus Bradyrhizobium, a type of rhizobia associated with leguminous plants.

[0051] Brevundimonas is a genus of proteobacteria, characterized by Gram-negative, non-fermentative, aerobic rod-shaped bacteria. Brevundimonas species are ubiquitous in the environment.

[0052] Desulfovibrio is a genus of Gram-negative sulfate-reducing bacteria that is commonly found in aquatic environments rich in organic matter and in flooded soils.

[0053] Microbacterium is a genus of Gram-positive endophytic fungi that resides within plant hosts and does not cause disease symptoms.

[0054] Sphingomonas is a genus of Gram-negative, rod-shaped, chemoheterotrophic, and obligate aerobic bacteria.

[0055] Varioborax is a genus of Gram-negative aerobic bacteria that can grow under a variety of conditions. Belonging to the Proteobacteria subclass, it can metabolically utilize several natural compounds produced from plants and algae.

[0056] The specific bacteria investigated in this application include species of Bosea, Microbacterium, Sphingomonas, and Variovorax. However, it will be understood that other bacteria mentioned above are equally effective in preventing and treating diseases.

[0057] The disclosed inventive concept comprises any combination of two basic steps: (1) Gram-negative bacteria produce an LPS / lipid A compound; and (2) the LPS / lipid compound modulates TLR activity by altering a signaling pathway, thereby preventing or reversing diseases such as coccidiosis. In one embodiment, the LPS / lipid A compound produced by the bacteria selectively alters the TLR signaling pathway (including, but not limited to, TLR2, TLR3, TLR4, TLR6, TLR7, TLR8, and / or TLR9 receptors). The bacterial strain may be naturally occurring and may be found in a variety of environments and natural materials.

[0058] The LPS / lipid A compounds used herein can be obtained from bacterial strains by any suitable method, but in specific embodiments, they are extracted using the following standard multi-step LPS extraction protocol: (1) extract the lyophilized bacteria with a phenol / guanidine thiocyanate solution and collect the aqueous layer for lyophilization; (2) re-solubilize the lyophilized fraction in water; (3) ultrafilter the solubilized fraction to remove low molecular weight substances and salts; (4) affinity purify the high molecular weight fraction using a polymyxin B resin column such as Affi-prep polymyxin matrix material (Bio-Rad), from which the active fraction is eluted with 1% deoxycholate; optionally (5) further purification using size exclusion chromatography.

[0059] Disease prevention and treatment - Data

[0060] General Exam Information

[0061] This document presents non-limiting examples of compositions and methods for preventing and treating diseases in animals and humans. While the following methods are directed towards promoting the growth of poultry, it should be understood that the disclosed methods are applicable to other animals as well as humans. Therefore, the described growth-promoting methods and treatments are not intended for use in poultry only.

[0062] According to non-limiting embodiments of the present invention, the compound of the present invention is defined as a related substance containing bacterial biomass and bacterial supernatant as described above. The compound of the present invention was mixed with conventional feed to form a "feed mixture" supplemented in a certain ratio. This ratio was maintained throughout the test period. A flock of birds was divided into a control group that was fed only conventional corn-soybean feed and an experimental group that was fed the supplemented mixed feed.

[0063] The study was understood to determine the response and efficacy of a dried algal biomass feed component, which was added in a fixed amount to a commercially available corn-soybean mixed feed and ingested by floor-fed broilers. The study was conducted over 28 days, from day 0 to day 28. In particular, the therapeutic compound is freshwater algal biomass containing Gram-negative bacteria, which is provided as animal feed in combination with a feed additive such as soybean oil, preferably in a ratio of 1 part algal biomass to 2 parts soil oil. Once the biomass and feed additive are blended to the desired premix level, the blended batch is evenly injected or dispensed into a ribbon mixer containing the finished feed.

[0064] Two non-limiting embodiments of biomass provided as animal feed in combination with feed additives are disclosed. The biomass of the first embodiment comprises a cocktail blend of four bacteria, and the biomass of the second embodiment comprises a blend of three bacteria. More or fewer bacteria may be included as part of the blend.

[0065] In the first embodiment, a blend of four bacteria from the genera Variovorax, Sphingomonas, Brevundimonas, and Microbacterium is provided in biomass, preferably in an amount between approximately 100.0 g and 150.0 g per ton of finished feed, more preferably in an amount between approximately 120.0 g and 130.0 g per ton of finished feed, and most preferably, though not exclusively, in an amount of approximately 126.0 g per ton of sample, providing good efficacy without waste.

[0066] The amounts of bacteria forming the blend may be varied. As a non-limiting example, both Variovorax and Bravendimonas preferably represent about 30.0g to 60.0g per ton of finished feed, more preferably about 40.0g to 50.0g per ton of finished feed, and most preferably about 45.0g per ton of finished feed; while Sphingomonas preferably represent about 15.0g to 45.0g per ton of finished feed, more preferably about 25.0g to 35.0g, and most preferably about 30.0g; and Microbacterium preferably represent about 0.1g to 20.0g, more preferably about 1.0g to 10.0g, and most preferably about 6.0g.

[0067] In the second embodiment, the blend of three bacteria from the genera Sphingomonas, Brevundimonas, and Microbacterium is preferably provided in the biomass in an amount between about 60.0 g and about 100.0 g per ton of finished feed, more preferably in an amount between about 70.0 g and about 90.0 g per ton of finished feed, and most preferably, though not exclusively, in an amount of about 81.0 g per ton of feed, which has good efficacy without waste.

[0068] The amounts of bacteria forming the blend may be varied. As a non-limiting example, Bravendimonas preferably amounts to about 30.0g to 60.0g per ton of finished feed, more preferably about 40.0g to 50.0g, and most preferably about 45.0g per ton of finished feed; Sphingomonas preferably amounts to about 15.0g to 45.0g per ton of finished feed, more preferably about 25.0g to 35.0g, and most preferably about 30.0g; and Microbacterium preferably amounts to about 0.1g to 20.0g per ton of finished feed, more preferably about 1.0g to 10.0g, and most preferably about 6.0g.

[0069] Test treatment methods

[0070] A total of 1,680 mixed-sex broiler chicks were obtained from a commercial hatchery on day 0 (hatching and placement day). The mixed-sex broiler chicks (50:50 sex ratio) were each replicated and randomly assigned on day 0 to one of several test group enclosures based on body weight. Only antibiotic-free birds were procured, and coccidiosis vaccine was not administered at the hatchery or during the study. Chicks were evaluated upon receipt for signs of disease and other complications that could affect the study results. Weakened birds were humanely sacrificed. Birds were not replaced during the study. There were 20 bird replicas, with 12 replicas per treatment group. There were 7 treatment groups.

[0071] After examination, the chicks' weight was measured and they were assigned to different treatment groups using a randomized block design. The weight distribution between treatment groups was evaluated before feeding by comparing the standard deviation of the mean weights of each treatment group relative to the control group. In this study, a weight distribution between groups was considered acceptable if the difference between the control and treatment groups was within one standard deviation.

[0072] All birds were given a nutritionally appropriate diet containing algal fermentation of this composition as pellets, and were given ad libitum access to their respective therapeutic diets from hatching to 28 days of age. The birds were raised in built-up litter to further mimic the stress conditions commonly experienced in poultry farming.

[0073] All feed was ad libitum, without restriction to complete feeding, except for an 8-hour fasting period on day 7 prior to cocci exposure, which involved feeding all birds an oocyst-inoculated feed containing a mixture of Eimeria acervulina, Eimeria maxima, and Eimeria tenella. Dietary requirements for protein, lysine, methionine, methionine + cystine, arginine, threonine, tryptophan, total phosphorus, available phosphorus, total calcium, dietary sodium, and dietary choline were met by adjusting the concentrations of components in corn and soybean meal, as well as the concentrations of other adjuncts commonly used in poultry production.

[0074] During the trial period, the birds were observed at least three times daily for evidence of health, behavior, and toxicity. The enclosures were monitored for environmental conditions, including temperature, lighting, water, feed, bedding condition, and any unexpected house conditions / events. Mortality was checked daily. All dead or dying broilers were examined. Deceased individuals were recorded (date and weight) and examined (internal and external mass).

[0075] Cocci-Exposure On day 7, all birds were given oocyst-inoculated feed containing a mixture of Eimeria aselbrina, Eimeria maxima, and Eimeria tenera. Sufficient feed was accurately weighed and supplied so that the birds consumed an average of 100% of the fill volume. Prior to exposure, all birds were starved for 8 hours. The inoculated feed was given to the birds. After a certain period, all remaining inoculated feed was removed and weighed to ensure that the consumption was equal for each enclosure and for each individual bird. The amount of feed (both added and removed) was recorded in the feed record for each enclosure.

[0076] Testing - Grouping

[0077] The following seven test groups were established. [Table 1-1]

[0078] Test Results

[0079] In the following, "FCR" refers to "Feed Conversion Rate." Conventionally, FCR refers to a ratio (or rate) that measures the efficiency with which animals convert feed into specific products.

[0080] In the following, "VP-UG" refers to the aforementioned therapeutic compound "UGA V. paradoxus biomass".

[0081] In the following, "VP-BS" refers to the aforementioned therapeutic compound "BioSource V. Paradoxus Biomass".

[0082] In the following, "Sym-VP" refers to the aforementioned "Symbiont Cocktail w / V. Paradoxus".

[0083] In the following, "Sym" refers to the aforementioned "Symbiont Cocktail w / oV. Paradoxus".

[0084] The following data compares 125g / ton of Symbiont cocktail containing V. paradoxus to 126g / ton of a blend of the same cocktail, and 80g / ton of Symbiont cocktail without V. paradoxus to 81g / ton of the same cocktail. However, the ratios of each component were the same.

[0085] Data sheet

[0086] The following table, together with the attached figures, provides support for the efficacy of the compositions and therapeutic methods of the present invention disclosed herein.

[0087] [Table 1-2]

[0088] [Table 2]

[0089] [Table 3]

[0090] [Table 4]

[0091] [Table 5]

[0092] result

[0093] In general, the analysis of the results based on the above table and the attached graphs shown in Figures 1 to 25 supports the conclusion that the use of the innovative compound in the treatment of poultry exposed to coccidiosis shows a significant improvement in the health of affected poultry compared to untreated poultry. The following positive results were observed in different bacterial variations of the disclosed Concept of the Invention composition.

[0094] The results can be summarized as follows:

[0095] FCR showed improvement in sample poultry treated with the disclosed composition compared to untreated birds exposed to the disease.

[0096] Examination of the sacrificial sample birds revealed that the mean lesion scores in both the duodenum and cecum of sample poultry treated with the disclosed composition were lower than those of untreated, disease-exposed birds. Furthermore, the mortality rate of sample poultry treated with the disclosed composition was lower than that of untreated, disease-exposed poultry. This data indicates that including two or more of Algolifer sp., Bosea sp., Brevundimonas sp., Desulfovibrio sp., Microbacterium sp., Sphingomonas sp., and Variovorax sp. in the therapeutic compound results in improvements in FCR, mortality, and lesion scores compared to untreated, disease-exposed birds.

[0097] Various bacterial combinations yielded different results. As a non-limiting example, regarding lesion scores, this study revealed that the combination of Bosea nasudae, Microbacterium, and Sphingomonas in the therapeutic compound was not enhanced by the addition of Variovorax paradoxus. Other combinations containing Variovorax paradoxus also showed excellent results.

[0098] The average body weight of sample poultry treated with the disclosed composition is greater than the average body weight of untreated birds exposed to the disease.

[0099] As a result of treatment with the disclosed compositions of the present invention, an improvement in the overall health of disease-exposed poultry was achieved without the use of antibiotics.

[0100] Overall, the compositions of the present invention represent a cost-effective and practical approach to treating disease conditions in animals. [Item 1] A composition for treating animal diseases through the regulation of the TLR pathway, wherein the composition comprises an effective amount of algal biomass as a component of finished feed, the algal biomass comprising at least two bacteria selected from the group consisting of Algoriphagus sp., Bosea sp., Brevundimonas sp., Desulfovibrio sp., Microbacterium sp., Sphingomonas sp., and Variovorax sp. [Item 2] A composition for the treatment of animal diseases, wherein the composition comprises algal biomass as part of a finished feed, the algal biomass essentially consisting of two or more bacteria selected from the group consisting of Algolifera sp., Bosea sp., Brevundimonas sp., Desulfovibrio sp., Microbacterium sp., Sphingomonas sp., and Variovorax sp. [Item 3] The composition according to item 2, wherein the disease being treated is coccidiosis. [Item 4] The composition described in item 2, wherein the algal biomass is ingested by animals in an amount of approximately 60.0 g to approximately 150.0 g per ton of finished feed. [Item 5] The composition described in item 4, wherein the algal biomass is ingested by animals in an amount of approximately 60.0 g to approximately 100.0 g per ton of finished feed. [Item 6] The composition according to item 5, wherein the aforementioned algal biomass contains three types of bacteria. [Item 7] The composition according to item 6, wherein the first bacterium represents approximately 40.0g to 50.0g per ton of finished feed, the second bacterium represents approximately 25.0g to 35.0g per ton of finished feed, and the third bacterium represents approximately 1.0g to 10.0g per ton of finished feed. [Item 8] The composition according to item 7, wherein the three types of bacteria include Brevundimonas sp., Sphingomonas sp., and Microbacterium sp. [Item 9] The composition according to item 8, comprising Bravendimonas sp. as the first bacterium, Sphingomonas sp. as the second bacterium, and Microbacterium sp. as the third bacterium. [Item 10] The composition described in item 4, wherein the algal biomass is ingested by animals in an amount of approximately 100.0 g to approximately 150.0 g per ton of finished feed. [Item 11] The composition according to item 10, wherein the algal biomass is ingested by animals in an amount of approximately 100.0 g to approximately 150.0 g per ton of finished feed. [Item 12] The composition according to item 11, wherein the aforementioned algal biomass contains four types of bacteria. [Item 13] The composition according to item 12, wherein the first and second bacteria represent approximately 40.0 g to 50.0 g per ton of finished feed, the third bacteria represent approximately 25.0 g to 35.0 g per ton of finished feed, and the fourth bacteria represent approximately 1.0 g to 10.0 g per ton of finished feed. [Item 14] The composition according to item 13, wherein the four types of bacteria include Variovorax sp., Bravendimonas sp., Sphingomonas sp., and Microbacterium sp. [Item 15] The composition according to item 14, wherein Variovorax sp. comprises a first bacterium, Bravendimonas sp. comprises a second bacterium, Sphingomonas sp. comprises a third bacterium, and Microbacterium sp. comprises a fourth bacterium. [Item 16] A method for treating an animal for subclinical or clinical coccidiosis by modulating the TLR pathway, the method comprising administering a biomass-based composition containing 2 or more bacterial compounds in an amount effective for treating subclinical or clinical coccidiosis, wherein the 2 or more bacteria are selected from the group consisting of Algolifera sp., Bosea sp., Bravendimonas sp., Desulfovibrio sp., Microbacterium sp., Sphingomonas sp., and Variovorax sp. [Item 17] The method according to item 16, wherein the biomass-based composition is ingested by animals in an amount of approximately 60.0 g to approximately 150.0 g per ton of finished feed. [Item 18] The biomass-based composition according to item 16, wherein the biomass-based composition essentially consists of three types of bacteria and is ingested by animals in an amount of approximately 60.0 g to approximately 100.0 g per ton of finished feed. [Item 19] The composition according to item 18, wherein the three types of bacteria include Brevundimonas sp., Sphingomonas sp., and Microbacterium sp. [Item 20] The biomass-based composition according to item 16, wherein the biomass-based composition essentially consists of four types of bacteria, and is ingested by animals in an amount of approximately 100.0 g to approximately 150.0 g per ton of finished feed. [Item 21] The composition according to item 20, wherein the four types of bacteria include Variovorax sp., Bravendimonas sp., Sphingomonas sp., and Microbacterium sp.

Claims

1. A composition for treating animal diseases through the regulation of at least one TLR pathway, wherein the composition comprises bacterial biomass as a component of the finished feed, and the bacterial biomass comprises three types of bacteria: Bravendimonas sp., Microbacterium sp., and Sphingomonas sp. The aforementioned at least one TLR pathway is selected from the group consisting of TLR2, TLR3, TLR4, TLR6, TLR7, TLR8, and TLR9 pathways, and The amount of Bravendimonas sp. is 30.0g to 60.0g per ton of finished feed. The amount of Microbacterium sp. is 1.0g to 10.0g per ton of finished feed. The amount of Sphingomonas sp. is 15.0g to 45.0g per ton of finished feed. A composition.

2. The composition according to claim 1, wherein the disease to be treated is an intestinal disease.

3. The composition according to claim 2, wherein the intestinal disease is coccidiosis.

4. The composition according to claim 1, wherein the bacterial biomass comprises three types of bacteria.

5. The composition according to claim 1, wherein the animal being treated is a poultry.

6. A composition for treating animal diseases through the regulation of at least one TLR pathway, wherein the composition comprises bacterial biomass as a component of the finished feed, and the bacterial biomass consists of three species: Bravendimonas sp., Microbacterium sp., and Sphingomonas sp. The aforementioned at least one TLR pathway is selected from the group consisting of TLR2, TLR3, TLR4, TLR6, TLR7, TLR8, and TLR9 pathways, and The amount of Bravendimonas sp. is 30.0g to 60.0g per ton of finished feed. The amount of Microbacterium sp. is 1.0g to 10.0g per ton of finished feed. The amount of Sphingomonas sp. is 15.0g to 45.0g per ton of finished feed. A composition.

7. The composition according to claim 6, wherein the disease to be treated is an intestinal disease.

8. The composition according to claim 7, wherein the intestinal disease is coccidiosis.

9. The composition according to claim 6, wherein the animal being treated is a poultry.

10. A composition for treating animal diseases through the regulation of at least one TLR pathway, wherein the composition comprises bacterial biomass as part of a finished feed, and the bacterial biomass comprises four species: Bravendimonas sp., Microbacterium sp., Sphingomonas sp., and Variovorax sp. The at least one TLR pathway is selected from the group consisting of TLR2, TLR3, TLR4, TLR6, TLR7, TLR8, and TLR9 pathways. and, The amount of Bravendimonas sp. is 30.0g to 60.0g per ton of finished feed. The amount of Microbacterium sp. is 1.0g to 10.0g per ton of finished feed. The amount of Sphingomonas sp. is 15.0g to 45.0g per ton of finished feed. The amount of Varioborax sp. should be 30.0g to 60.0g per ton of finished feed. A composition.

11. The composition according to claim 10, wherein the disease to be treated is an intestinal disease.

12. The composition according to claim 11, wherein the intestinal disease is coccidiosis.

13. The composition according to claim 10, wherein the animal to be treated is a poultry.

14. A method for treating poultry for subclinical or clinical coccidiosis by modulating at least one TLR pathway, comprising orally administering a composition according to any one of claims 1 to 13 in an amount of 45.0 g to 150.0 g per ton of finished feed, The method wherein the at least one TLR pathway is selected from the group consisting of TLR2, TLR3, TLR4, TLR6, TLR7, TLR8, and TLR9 pathways.

15. The method according to claim 14, wherein the composition is fed to an animal in an amount of 60.0 g to 150.0 g per ton of finished feed.

16. The method according to claim 14, wherein the composition consists of three types of bacteria and is fed to animals in an amount of 60.0 g to 100.0 g per ton of finished feed.

17. The method according to claim 16, wherein the three types of bacteria include Bravendimonas sp., Sphingomonas sp., and Microbacterium sp.

18. The method according to claim 14, wherein the composition consists of four types of bacteria and is fed to animals in an amount of 100.0 g to 150.0 g per ton of finished feed.

19. The method according to claim 18, wherein the four types of bacteria include Variovorax sp., Bravendimonas sp., Sphingomonas sp., and Microbacterium sp.

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