Compositions of hemp hull fiber and probiotics and methods of using same

Abstract

Provided are compositions comprising a plant mass, e.g., a hemp hull fiber, comprising a cellulose, a hemicellulose, a lignan, a lignin, or a combination thereof (e.g., a prebiotic composition), such compositions further comprising a plurality of bacteria (e.g., a synbiotic composition), and methods of preparing and using the same. The compositions are useful as food or dietary supplements or for the treatment or prevention of disease.

Description

COMPOSITIONS OF HEMP HULL FIBER AND PROBIOTICS AND METHODS OF USING SAMECROSS REFERENCE TO A RELATED APPLICATION

[0001] This PCT application claims the benefit of U.S. Provisional Patent ApplicationNo. 63 / 551,466, filed February 8, 2024, the entirety of which is incorporated by reference herein.FIELD

[0002] The present disclosure relates to compositions comprising a probiotic, e.g., bacteria and / or yeast, and a plant mass, such as hemp hull fiber, for dietary or therapeutic use. In some aspects, the probiotic, e.g., bacteria and / or yeast, is capable of catabolizing useful components of the plant mass (e.g., a cellulose, a hemicellulose, a lignan, a lignin, or a combination thereof).BACKGROUND

[0003] Consumers continue to seek nutritional solutions that enhance health and wellbeing. Seventy nine percent of global consumers seek to improve their diet (FMCG Gurus. FMCG Gurus: Top Ten Trends for 2021:, 2021). This quest for an improved diet can be associated with improved health, where, for example, in the U.S. 86% of current healthcare spending addresses preventable health conditions (Holman HR. The Relation of the Chronic Disease Epidemic to the Health Care Crisis. ACR Open Rheumatol. 2020;2(3): 167-173. doi: 10.1002 / acr2.11114). Holistic dietary approaches that emphasize less processed foods are gaining popularity among consumers, which may address the current gap in dietary intakes (FMCG Gurus. FMCG Gurus: Top Ten Trends for 2021:, 2021). For example, only 15% of U.S. consumers consume the recommended amount of fruit per day and only 10% of U.S. boys aged 1-3 and 15% of U.S. girls aged 1-3 consume the recommended amount of vegetables per day (Wallace TC, Bailey RL, Blumberg JB, et al. Fruits, vegetables, and health: A comprehensive narrative, umbrella review of the science and recommendations for enhanced public policy to improve intake. Crit Rev Food Sci Nutr. 2020;60(13):2174-2211. doi: 10.1080 / 10408398.2019.1632258).

[0004] While consumers may not be hitting targets for fruit and vegetable intake, they are very interested in functional foods. For example, fifty-six percent of global consumers are researching ingredients to boost health, and sixty percent of global consumers are interested in food and beverages that promote digestive health (FMCG Gurus. FMCG Gurus: Top Ten Trends for 2021:, 2021). New innovations in food ingredients can address specific consumer needs.

[0005] Hemp, Cannabis saliva, is a plant used for fiber, food, and medicinal purposes. Many components of the plant offer value-added function. For example, the hemp hearts (seeds) can be processed for oil and protein, while the hemp seed hull, the outer coating of the hemp heart, is rich in dietary fiber, and also contains protein and fat. Hemp seed hulls are a source of dietary fiber and a rich source of bioactives, including phytochemicals.

[0006] Bio Gut Fiber ("BGF") is a whole food ingredient made from hemp seed hulls (i.e., a comestible hemp seed hull powder) that provides holistic nutrition and digestive health, and can be incorporated into finished product formats. As a source of dietary fiber and bioactive compounds, a hemp hull composition, such as BGF, may exert a benefit on digestive health through various mechanisms. In particular, BGF comprises useful plant components (e.g., cellulose, hemicellulose, lignan, and lignin) that may be metabolized by particular gut microbes to produce substances useful for maintaining and / or improving gut health, such as postbiotics containing, e.g., metabolites of a cellulose, a hemicellulose, a lignan, a lignin, or a combination thereof.

[0007] Further, consumers have a great interest in prebiotics and functional probiotics, and dietary or therapeutic compositions leveraging the ability of prebiotics and / or probiotics to regulate the gut microbiome. Taken together, there is a need for compositions of dietary fiber, including with useful microbes such as bacteria, yeast, or both. Such compositions are useful for improvement of health (e.g., gut health) and prevention or treatment of disease. In particular, there is a need for new compositions comprising useful plant components, e.g., a cellulose, a hemicellulose, a lignan, a lignin, or a combination thereof, such as a composition comprising BGF and a cellulose, a hemicellulose, a lignan, a lignin, or a combination thereof, as well as such compositions comprising beneficial bacteria capable of metabolizing them. The use of hemp hull fiber as a prebiotic provides unique advantages, such as enhanced digestive tolerance, overhighly fermentable fibers, such as inulin and reduce barriers to fiber consumption adherence. Such compositions would allow for an individual to introduce to their gastrointestinal tract not only useful plant components (e.g., a cellulose, a hemicellulose, a lignan, a lignin, or a combination thereof) that can be converted to beneficial metabolites, but also bacteria and / or yeast equipped to produce such beneficial metabolites.BRIEF SUMMARY

[0008] In some aspects, the present disclosure provides a composition comprising (i) a hemp hull fiber, and (ii) a plurality of bacteria, yeast, or both.

[0009] In some aspects, the hemp hull fiber comprises a cellulose, a hemicellulose, a lignan, a lignin, or a combination thereof.

[0010] In some aspects, the composition is formulated as a synbiotic composition.

[0011] In some aspects, the composition further comprises N-trans-caffeoyltyramine(NCT) and / or N-trans-feruloyltyramine (NFT). In some aspects, the hemp hull fiber comprises less than 2% wt / v N-trans-caffeoyltyramine (NCT) and / or N-trans- feruloyltyramine (NFT).

[0012] In some aspects, the present disclosure provides a composition comprising a plurality of bacteria, yeast, or both, and N-trans-caffeoyltyramine (NCT) and / or N-trans- feruloyltyramine (NFT). In some aspects, the composition comprises less than 2% wt / v N-trans-caffeoyltyramine (NCT) and / or N-trans-feruloyltyramine (NFT).

[0013] In some aspects, the plurality of bacteria comprises only one species or strain of bacteria. In some aspects, the plurality of bacteria comprises two or more species or strains of bacteria. In some aspects, the plurality of bacteria comprises bacteria of the genus Lacticaseibacillus (formerly part of the genus Lactobacillus). In some aspects, the plurality of bacteria comprises bacteria selected from Lacticaseibacillus rhamnosus. Lacticaseibacillus casei, Lacticaseibacillus paracasei. or a combination thereof. In some aspects, the plurality of bacteria does not comprise Blautia producta, Eggerthella lenla. or both. In some aspects, the plurality of bacteria comprises bacteria of the genus Enterococcus, Lactobacillus, Bifidobacterium, Lactococcus, Streptococcus, or a combination thereof. In some aspects, the plurality of bacteria comprises bacteria selected from Enterococcus faecalis, Lactobacillus reuteri, Bifidobacterium animalis,Bifidobacterium longum, Lactobacillus helveticus, Lactococcus lactis, Lactobacillus acidophilus, Streptococcus thermophiles, or a combination thereof. In some aspects, the plurality of bacteria comprises bacteria selected from Enterococcus faecalis BAA-2820, Lactobacillus reuteri BAA-2837, Bifidobacterium animalis subsp. Lactis BAA-2848, Bifidobacterium longum BAA-999, Lactobacillus helveticus BAA-2840, Lactococcus lactis subsp. Lactis ATCC 19435, Lactobacillus acidophilus BAA-2832, Streptococcus thermophilus BAA- 19258, or a combination thereof.

[0014] In some aspects, the plurality of bacteria comprises spores. In some aspects, the plurality of bacteria comprises vegetative cells. In some aspects, the plurality of bacteria comprises spores and vegetative cells.

[0015] In some aspects, the plurality of bacteria comprises a polynucleotide encoding an enzyme that catabolizes a cellulose, a hemicellulose, a lignan, or a lignin. In some aspects, the plurality of bacteria comprises recombinant bacteria genetically engineered to comprise the polynucleotide encoding the enzyme that catabolizes the cellulose, hemicellulose, lignan, or the lignin.

[0016] In some aspects, the plurality of yeast comprises only one species or strain of yeast. In some aspects, the plurality of yeast comprises two or more species or strains of yeast. In some aspects, the plurality of yeast comprises yeast of the genus Saccharomyces. In some aspects, the plurality of yeast comprises Saccharomyces cerevisiae. In some aspects, the plurality of yeast comprises Saccharomyces cerevisiae MYA-797.

[0017] In some aspects, the composition comprises (i) the hemp hull fiber, and (ii) the plurality of bacteria. In some aspects, the composition comprises (i) the hemp hull fiber, and (ii) the plurality of yeast. In some aspects, the composition comprises (i) the hemp hull fiber, (ii) the plurality of bacteria, and (iii) the plurality of yeast.

[0018] In some aspects, the hemp hull fiber is an extruded hemp hull fiber. In some aspects, the hemp hull fiber is not an extruded hemp hull fiber.

[0019] In some aspects, the hemp hull fiber comprises less than 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, 0.9%, 0.8%, 0.7%, 0.6%, 0.5%, 0.4%, 0.3%, 0.2%, 0.1%, 0.09%, 0.08%, 0.07%, 0.06%, 0.05%, 0.04%, 0.03%, 0.02%, or 0.01% w / w of inulin. In some aspects, the hemp hull fiber does not comprise a detectable amount of inulin.

[0020] In some aspects, the hemp hull fiber comprises insoluble fiber.

[0021] In some aspects, the composition is capable of producing one or more of the metabolites listed in Table 1. In some aspects, the composition further comprises one or more of the metabolites listed in Table 1.

[0022] In some aspects, the present disclosure provides a comestible composition comprising the composition disclosed herein and a nutritionally acceptable additive. In some aspects, the nutritionally acceptable additive comprises a prebiotic additive. In some aspects, the prebiotic additive comprises a prebiotic substance not present in the hemp hull fiber. In some aspects, the prebiotic additive comprises a prebiotic substance present in the hemp hull fiber. In some aspects, the nutritionally acceptable additive comprises a flavoring agent, an odor masking agent, a coloring agent, a mouthfeel agent, or a combination thereof.

[0023] In some aspects, the comestible composition is in liquid form. In some aspects, the comestible composition is in solid form.

[0024] In some aspects, the comestible composition comprises one or more capsules or tablets. In some aspects, the comestible composition comprises a crisp (e.g., a protein crisp).

[0025] In some aspects, the present disclosure provides an oral dosage form comprising a composition disclosed herein. In some aspects, the composition comprises a solution, slurry, suspension, or emulsion. In some aspects, the composition comprises a solid dosage form. In some aspects, the solid dosage form comprises a powder, a capsule, or a tablet. In some aspects, the oral dosage form comprises two or more capsules or tablets. In some aspects, the oral dosage form is formulated for delivery to the intestines. In some aspects, the oral dosage form comprises an enteric polymer.

[0026] In some aspects, a composition, a comestible composition, or an oral dosage form disclosed herein comprises a “Good Source” level of fiber or a “High” level of fiber. In some aspects, a composition, a comestible composition, or an oral dosage form disclosed herein comprises about 2.5 grams to about 4.9 grams of fiber. In some aspects, a composition, a comestible composition, or an oral dosage form disclosed herein comprises about 2.8 grams of fiber. In some aspects, a composition, a comestible composition, or an oral dosage form disclosed herein comprises about 5 grams or more of fiber.

[0027] In some aspects, the present disclosure provides a method of preparing a composition, a comestible composition, or an oral dosage form provided herein, comprising a step of pre-treating the plurality of bacteria. In some aspects, the step of pretreating comprises germinating a plurality of spores. In some aspects, the step of pretreating comprises growing a plurality of bacterial cells to logarithmic phase. In some aspects, the present disclosure provides a method of preparing a composition, a comestible composition, or an oral dosage form disclosed herein, comprising growing the plurality of yeast cells to a logarithmic phase.

[0028] In some aspects, the present disclosure provides a method of treating or reducing the risk of a disease, disorder, or dysbiosis, of improving gut epithelial barrier integrity, of increasing gut transepithelial electrical resistance (TEER), of increasing gut microbial diversity, of reducing one or more symptoms of gastrointestinal discomfort, of reducing the risk of gastrointestinal discomfort, or of improving gastrointestinal comfort, comprising administering an effective amount of a composition, a comestible composition, or an oral dosage form disclosed herein to a subject in need thereof. In some aspects, the present disclosure provides a method of treating or reducing the risk of a disease, disorder, or dysbiosis, of improving gut epithelial barrier integrity, of increasing gut transepithelial electrical resistance (TEER), of increasing gut microbial diversity, of reducing one or more symptoms of gastrointestinal discomfort, of reducing the risk of gastrointestinal discomfort, or of improving gastrointestinal comfort, comprising administering to a subject in need thereof an effective amount of: a hemp hull fiber comprising a cellulose, a hemicellulose, a lignan, a lignin, or a combination thereof. In some aspects, the subject is additionally administered a plurality of bacteria, yeast, or both. In some aspects, the hemp hull fiber and the plurality of bacteria, yeast or both are not contained within the same dosage form. In some aspects, the hemp hull fiber and the plurality of bacteria, yeast, or both are contained within the same dosage form.

[0029] In some aspects, the one or more symptoms of gastrointestinal discomfort is assessed by one or more of: Digestion Associated Quality of Life Questionnaire (DQLQ), PROMIS Belly Pain 5a, PROMIS GI Gas and Bloating 13a, and PROMIS Anxiety 4a. In some aspects, the one or more symptoms of gastrointestinal discomfort is one or more of abdominal pain, flatulence, bloating, and anxiety. In some aspects, the one or more symptoms of gastrointestinal discomfort is improved more than the level of improvementobserved following administration of a mass of inulin equivalent to the mass of the hemp hull fiber administered to the subject. In some aspects, the risk of gastrointestinal discomfort is decreased more than the level of decrease observed following administration of a mass of inulin equivalent to the mass of the hemp hull fiber administered to the subject. In some aspects, the risk of gastrointestinal comfort is improved more than the level of improvement observed following administration of a mass of inulin equivalent to the mass of the hemp hull fiber administered to the subject.

[0030] In some aspects, the present disclosure provides a method of increasing the abundance of Lactobacilliaceae in the gut of a subject in need thereof, comprising administering to the subject an effective amount of: a hemp hull fiber comprising a cellulose, a hemicellulose, a lignan, a lignin, or a combination thereof. In some aspects, the subject is additionally administered a plurality of bacteria, yeast, or both. In some aspects, the hemp hull fiber and the plurality of bacteria, yeast, or both are not contained within the same dosage form. In some aspects, the hemp hull fiber and the plurality of bacteria, yeast, or both are contained within the same dosage form.

[0031] In some aspects, the plurality of bacteria, yeast, or both further comprises and / or the hemp hull fiber comprises N-trans-caffeoyltyramine (NCT) and / or N-trans- feruloyltyramine (NFT).

[0032] In some aspects, the disease, disorder, or dysbiosis is selected from Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). In some aspects, the disease, disorder, or dysbiosis is a gastrointestinal disease, disorder, or dysbiosis. In some aspects, the gastrointestinal disease, disorder, or dysbiosis is selected from irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), Crohn's disease (CD), ulcerative colitis (UC), celiac disease, necrotizing enterocolitis, indeterminate colitis, chronic colitis, HIV enteropathy, Helicobacter gastritis, NSAID-enteropathy / enteritis, pouchitis, discontinuous or patchy disease, ileal inflammation, extracolonic inflammation, granulomatous inflammation in response to ruptured crypts, aphthous ulcers, transmural inflammation, microscopic colitis, diverticulitis, diversion colitis, short bowel syndrome, GI mucositis, chemotherapy induced mucositis, radiation induced mucositis, or interstitial cystitis.

[0033] In some aspects, the abundance of Lactobacillaceae in the gut of the subject is increased following administration. In some aspects, the abundance of bacteria of thefamily Enterob acteriaceae in the gut of the subject is not increased following administration.

[0034] In some aspects, the concentration of a short-chain fatty acid in the gut of the subject is increased following administration. In some aspects, the short-chain fatty acid comprises acetic acid, propanoic acid, or butyric acid.

[0035] In some aspects, a composition, a comestible composition, or an oral dosage form disclosed herein is administered as two or more capsules daily. In some aspects, the method comprises: obtaining a fecal sample from the subject, determining the abundance of Lactobacillaceae present in the fecal sample from the subject, and administering the composition to the subject if the abundance of Lactobacillaceae present in the fecal sample from the subject is less than about 0.001%, 0.01%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 1.5%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 30%, 35%, 40%, 45%, or 50% relative to the total abundance of bacteria in the fecal sample. In some aspects, the method comprises: obtaining a fecal sample from the subject, determining the abundance of Lactobacillaceae present in the fecal sample from the subject, obtaining a fecal sample from a healthy donor, determining the abundance of Lactobacillaceae present in the fecal sample from the healthy donor, and administering the composition to the subject if the abundance of Lactobacillaceae present in the fecal sample is less than 10% relative to the abundance of Lactobacillaceae present in the fecal sample from the healthy donor. In some aspects, the method comprises: obtaining a fecal sample from the subject, determining the amount of a cellulose, a hemicellulose, a lignin, a lignan, or a combination thereof present in the fecal sample from the subject, obtaining a fecal sample from a healthy donor, determining the amount of the cellulose, the hemicellulose, the lignin, the lignan, or the combination thereof present in the fecal sample from the healthy donor, and administering the composition to the subject if the amount of the cellulose, the hemicellulose, the lignin, the lignan, or the combination thereof present in the fecal sample from the subject is more than the amount of the cellulose, the hemicellulose, the lignan, the lignin, or the combination thereof present in a fecal sample from the healthy donor.

[0036] In some aspects, the method comprises: obtaining a fecal sample from the subject, determining the amount of a cellulose, a hemicellulose, a lignin, a lignan, or acombination thereof present in the fecal sample from the subject, obtaining a fecal sample from a healthy donor, determining the amount of the cellulose, the hemicellulose, the lignin, the lignan, or the combination thereof present in the fecal sample from the healthy donor, and administering the composition to the subject if the amount of the cellulose, the hemicellulose, the lignin, the lignan, or the combination thereof present in the fecal sample is more than the amount of the cellulose, the hemicellulose, the lignin, the lignan, or the combination thereof present in the fecal sample from the healthy donor.BRIEF DESCRIPTION OF THE DRAWINGS

[0037] Fig. 1 A through 1 J show growth kinetics between test strains (Fig. 1 A, Enterococcus faecalis BAA-2820,' Fig. IB, Lactobacillus reuteri BAA-2837,' Fig. 1C, Bifidobacterium animalis subsp. Lactis BAA-2848,' Fig. ID, Bifidobacterium longum BAA-999,' Fig. IE, Saccharomyces cerevisiae ALYA-797,' Fig. IF, Lactobacillus helveticus BAA-2840,' Fig. 1G, Lactococcus lactis subsp. Lactis ATCC 19435,' Fig. 1H, Lactobacillus acidophilus BAA-2832,' Fig. II, Streptococcus thermophilus BAA-19258,' Fig. 1 J, equal volume mixture of all strains) cultured in media or media supplemented with a hemp hull fiber composition.

[0038] Fig. 2 shows a bar graph of the growth of L. paracasei in the presence of 5, 10, and 20 mg / mL of a hemp hull fiber powder composition after 24 hours of incubation at 37 °C, relative to controls of L. paracasei in growth media (HiVeg) without the hemp hull fiber powder composition, HiVeg only, and HiVeg and 20 mg / mL of the hemp hull fiber powder composition.

[0039] Fig. 3 shows a bar graph of growth of L. rhamnosus and L. casei in the presence of 20 mg / mL of the hemp hull fiber powder composition after 24 hours of incubation at 37 °C, relative to a control of bacteria in growth media (HiVeg) without the hemp hull fiber powder composition.

[0040] Fig. 4A and 4B show plots of Digestion Associated Quality of Life Questionnaire Scores from Modified Intent to Treat Analysis (Fig. 3 A) and Per Protocol Analysis (Fig. 3B).

[0041] Fig. 5 A and 5B show plots of Belly Pain Scores from Modified Intent to Treat Analysis (Fig. 4A) and Per Protocol Analysis (Fig. 4B).

[0042] Fig. 6A and 6B show plots of Gas and Bloating Scores from Modified Intent to Treat Analysis (Fig. 6A) and Per Protocol Analysis (Fig. 6B).

[0043] Fig. 7A and 7B show plots of Anxiety Scores from Modified Intent to Treat Analysis (Fig. 7A) and Per Protocol Analysis (Fig. 7B).DETAILED DESCRIPTION OF THE INVENTION

[0044] Provided herein are compositions comprising a plant mass, such as a hemp hull fiber, (e.g., a prebiotic composition), for use in a comestible or an oral dosage form suitable for improving gut health. Also provided herein are compositions comprising plant mass, such as a hemp hull fiber, and probiotic bacteria, yeast, or both (e.g., a synbiotic composition), for use in a comestible or oral dosage form suitable for improving gut health. In some aspects, the compositions described herein comprise a plurality of bacteria, yeast, or both capable of metabolizing a useful plant component (e.g., a cellulose, a hemicellulose, a lignin, a lignan, or a combination thereof). In some aspects, administration of a disclosed composition increases the abundance of useful plant component metabolites (e.g., a metabolites of a cellulose, a hemicellulose, a lignan, or a lignin or one or more metabolites identified in Table 1) in a subject's gut. In some aspects, the plant mass, such as a hemp hull fiber, comprises one or more substances that enhance the growth of the administered beneficial bacterial species compared to growth of the bacterial species without the plant mass, and such growth can be evaluated in vitro. In some aspects, the compositions comprise N-trans-caffeoyltyramine (NCT) and / or N-trans-feruloyltyramine (NFT) and further comprise a plurality of bacteria, yeast, or both. In some aspects, administration of the composition improves gut health or maintains gut health in the subject, such as through maintaining gut epithelial barrier integrity. Additional aspects are provided throughout the present disclosure.

[0045] As compared to other sources of insoluble fiber, such as inulin, hemp hull fiber surprisingly provides digestive and metabolic benefits while providing a higher tolerance profile for digestive symptoms, including one or more of abdominal pain, bloating, flatulence, and accompanying anxiety associated with these digestive symptoms. Further, as described herein, compositions of a plant mass, such as a hemp hull fiber, not only provide digestive and metabolic benefits while providing a higher tolerance profile for digestive symptoms, but also provide enhanced metabolite production when combined witha probiotic, such as bacteria, yeast, or a combination of both. Compositions as described herein comprising a plant mass, such as a hemp hull fiber, a probiotic, such as bacteria, yeast, or a combination of both, and / or the metabolites produced from a combination of the plant mass and the probiotic, provide advantages over insoluble fiber compositions lacking these components.

[0046] To facilitate an understanding of the disclosure disclosed herein, a number of terms and phrases are defined.Definitions

[0047] As used herein, the term "a" or "an" refers to one or more; for example, "a lignan," is understood to represent one or more lignans. As such, the terms "a" (or "an"), "one or more," and "at least one" can be used interchangeably herein.

[0048] The term "and / or" where used herein is to be taken as specific disclosure of each of the two specified features or components with or without the other. Thus, the term "and / or" as used in a phrase such as "A and / or B" herein is intended to include "A and B," "A or B," "A" (alone), and "B" (alone). Likewise, the term "and / or" as used in a phrase such as "A, B, and / or C" is intended to encompass each of the following aspects: A, B, and C; A, B, or C; A or C; A or B; B or C; A and C; A and B; B and C; A (alone); B (alone); and C (alone).

[0049] As used herein, wherever aspects are described with the language "comprising," otherwise analogous aspects described in terms of "consisting of' and / or "consisting essentially of' are also provided. As used herein, "comprising" is synonymous with "including," "containing," or "characterized by," and is inclusive or open-ended and does not exclude additional, unrecited elements or method steps. As used herein, "consisting of excludes any element, step, or ingredient not specified in the claim element. As used herein, "consisting essentially of does not exclude materials or steps that do not materially affect the basic and novel characteristics of the claim.

[0050] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure is related.

[0051] Units, prefixes, and symbols are denoted in their Systeme International de Unites (SI) accepted form. Numeric ranges are inclusive of the numbers defining the range. Unless otherwise indicated, nucleotide sequences are written left to right in 5' to 3'orientation. Amino acid sequences are written left to right in amino to carboxy orientation. The headings provided herein are not limitations of the various aspects of the disclosure, which can be had by reference to the specification as a whole. Accordingly, the terms defined immediately below are more fully defined by reference to the specification in its entirety.

[0052] The term "at least" prior to a number or series of numbers is understood to include the number adjacent to the term "at least," and all subsequent numbers or integers that could logically be included, as clear from context. For example, the number of nucleotides in a nucleic acid molecule must be an integer. For example, "at least 18 nucleotides of a 21 -nucleotide nucleic acid molecule" means that 18, 19, 20, or 21 nucleotides have the indicated property. When "at least" is present before a series of numbers or a range, it is understood that "at least" can modify each of the numbers in the series or range. "At least" is also not limited to integers (e.g., "at least 5%" includes 5.0%, 5.1%, 5.18%) without consideration of the number of significant figures.

[0053] As described herein, any concentration range, percentage range, ratio range, or integer range is to be understood to include the value of any integer within the recited range and, when appropriate, fractions thereof (such as one tenth and one hundredth of an integer), unless otherwise indicated.

[0054] As used herein, the term "subject" as used herein refers to an animal, preferably a mammal. In some aspects, the subject is a veterinary, companion, farm, laboratory or zoological animal. In other aspects, the subject is a human. Recent studies have demonstrated that the "Western diet" of high amounts of fat, sugar, and protein is associated with changes in the gut microbiome of immigrants to countries with a high prevalence of individuals eating a Western diet. See Sonnenburg, Justin, et al. 2018. A Microbiota Assimilation. Cell Metabolism. 28(5):675-677. See also Vangay, P., et al. 2018. U.S. immigration westernizes the human gut microbiome. Cell. 175(4):962-972. In some aspects, the subject is an immigrant to a Western country. In some aspects, the subject is an immigrant to a Western country from an Asian country, such as a southeastern Asian country (e.g., China). In some aspects, the Western country is the United States of America. In some aspects, the subject lives in a Western country or a territory or jurisdiction under the control of the Western country. In some aspects, the subject lives in a Western country, but is not an immigrant from another country. In someaspects, a subject on a "Western diet" includes a subject regularly consuming highly- processed foods (such as, without limitation, white pasta, white bread, potato chips, pretzels, sweetened juice products, soft drinks, sweetened breakfast cereals, margarine, reconstituted meat products such as hot dogs, candy, cookies, and cakes), whether or not a subject on the Western diet resides in a country that is considered Western. Highly- processed foods contrast with, e.g., unprocessed or minimally processed foods such as, without limitation, fresh fruits, fresh vegetables, single-ingredient canned fruits, beans, intact whole grains, unprocessed meat, and dairy milk.

[0055] As used herein, the term "effective amount" means an amount of the compound, composition, or formulation containing the compound or composition, which is sufficient to significantly improve a dysbiosis, disease, or disorder, or reduce the risk of the dysbiosis, disease, or disorder. Of concern when determining an effective amount to be used in humans is balancing the desired effects (benefits) against risks associated with use of the compound or composition. At issue for such risk / benefit assessments is the types of adverse effects observed and the likelihood that they will occur. Also considered is the fact that the effective amount may vary with the particular dysbiosis, disease, or disorder, e.g., inflammatory bowel disease, the age and physical condition of the end user, the severity of the condition, the duration of the treatment, the particular carrier utilized, and like factors.

[0056] As used herein, Eggerthella lenta (E. lenta) refers to the bacterial species of the same name, and strains thereof, such as ATCC 43055 or ATC 25559. E. lenta includes bacteria having > 97% sequence identity to a 16S rDNA sequence of Eggerthella lenta, such as NCBI Reference Sequence NR_074377.1 or NR_037089.1.

[0057] As used herein, Lacticaseibacillus rhamnosus (L. rhamnosus), formerly Lactobacillus rhamnosus, refers to the bacterial species of the same name, and strains thereof, such as ATCC 7469. L. rhamnosus includes bacteria having > 97% sequence identity to a 16S rDNA sequence of L. rhamnosus, such as NCBI Reference Sequence NR_113332.1 orNR_043408.1.

[0058] As used herein, Lacticaseibacillus casei (L. casei), formerly Lactobacillus casei, refers to the bacterial species of the same name, and strains thereof, such as ATCC 393. L. casei includes bacteria having > 97% sequence identity to a 16S rDNA sequence of L. casei, such as NCBI Reference Sequence NR_118976.1 or NR_041893.1.

[0059] As used herein, Lacticaseibacillus paracasei (L. paracasei), formerly Lactobacillus paracasei, refers to the bacterial species of the same name, and strains thereof, such as ATCC 11578. L. paracasei includes bacteria having > 97% sequence identity to a 16S rDNA sequence of L. paracasei, such as NCBI Reference Sequence NR 117987.1 orNR_025880.1.

[0060] As used herein, Blautia producta (B. producta), formerly Ruminococcus productus, refers to the bacterial species of the same name, and strains thereof, such as ATCC 27340. B. producta includes bacteria having > 97% sequence identity to a 16S rDNA sequence of B. producta, such as NCBI Reference Sequence NR_ 115507.1 or NR_036776.1.

[0061] As used herein, Enterococcus faecalis (E. faecalis), formerly Streptococcus faecalis, refers to the bacterial species of the same name, and strains thereof, such as ATCC 19433 or BAA-2820. E. faecalis includes bacteria having > 97% sequence identity to a 16S rDNA sequence of E. faecalis, such as GenBank Reference Sequence AJ301831.1.

[0062] As used herein, Lactobacillus reuteri (L. reuteri), refers to the bacterial species of the same name, and strains thereof, such as ATCC 23272 or BAA-2837. L. reuteri includes bacteria having > 97% sequence identity to a 16S rDNA sequence of L. reuteri, such as GenBank Reference Sequence X76328.1.

[0063] As used herein, Bifidobacterium animalis (B. animalis), formerly Bifidobacterium longum subsp. animalis, refers to the bacterial species of the same name, and strains thereof, such as ATCC 25527 or Lactis BAA-2848. B. animalis includes bacteria having > 97% sequence identity to a 16S rDNA sequence of B. animalis, such as GenBank Reference Sequence D86185.1.

[0064] As used herein, Bifidobacterium longum (B. longum), refers to the bacterial species of the same name, and strains thereof, such as ATCC 15707 or BAA-999. B. longum includes bacteria having > 97% sequence identity to a 16S rDNA sequence of B. longum, such as GenBank Reference Sequence GU361823.1.

[0065] As used herein, Saccharomyces cerevisiae (S. cerevisiae) refers to the yeast species of the same name, and strains thereof, such as ATCC 9763 or MYA-797.

[0066] As used herein, Lactobacillus helveticus (L. helveticus), formerly Thermobacterium helveticum, refers to the bacterial species of the same name, and strainsthereof, such as ATCC 15009 or BAA-2840. L. helveticus includes bacteria having > 97% sequence identity to a 16S rDNA sequence of L. helveticus, such as GenBank Reference Sequence AB680751.1.

[0067] As used herein, Lactococcus lactis (L. laclis), formerly Bacterium laclis, refers to the bacterial species of the same name, and strains thereof, such as ATCC 19435. L. lactis includes bacteria having > 97% sequence identity to a 16S rDNA sequence of L. lactis, such as GenBank Reference Sequence M58837.1.

[0068] As used herein, Lactobacillus acidophilus (L. acidophilus), formerly Bacillus acidophilus, refers to the bacterial species of the same name, and strains thereof, such as ATCC 4356 or BAA-2832. L. acidophilus includes bacteria having > 97% sequence identity to a 16S rDNA sequence of L. acidophilus, such as GenBank Reference Sequence M58802.1.

[0069] As used herein, Streptococcus thermophilus (S. thermophilus), formerly Streptococcus salivarius subsp. thermophilus, refers to the bacterial species of the same name, and strains thereof, such as ATCC 19258 or BAA-19258. S. thermophilus includes bacteria having > 97% sequence identity to a 16S rDNA sequence of S. thermophilus, such as GenBank Reference Sequence X68418.1.

[0070] The reference sequences provided herein are exemplary and not intended to be limiting. A skilled artisan can identify alternative 16S DNA sequences of bacteria disclosed herein by searching standard databases, such as the United States National Center for Biotechnology Information (NCBI) database, which can be found at ncbi.nlm.nih.gov / nuccore.

[0071] As used herein, the term "abundance" as related to bacteria refers to the quantitative amount of bacteria present in, e.g., the gut microbiome of a subject or in a fecal sample from a subject. Abundance may be determined by quantitative genome sequencing, e.g., by quantitative polymerase chain reaction methods that determine a number of sequences in a given sample by mass, correlating to the abundance of bacteria containing those sequences. Abundance may alternatively be relative to a reference, such as relative to the abundance of a reference sequence in the same sample.

[0072] As used herein, the term "Bio Gut Fiber" or "BGF" refers to a processed version of hemp seed hulls that contains 65% or more dietary fiber. The fiber is composed of a mixture of primarily cellulose (about 40%), and lesser proportions of lignin (about 20%)and hemicellulose (about 16%). Hemp seed hulls are a rich source of bioactives (otherwise named as phytochemicals). For example, they are high in phenolic compounds (such as lignans), which are recognized for their health benefits and antioxidant potential. BGF contains a total phenolic content of about 16 mg GAE / g. Phenolic amides are a type of phenolics and can have specific bioactivity as described in the next sections. BGF contains the phenolic amides NCT and NFT at about 0.7 mg GAE / g. Where BGF or another composition comprising a plant mass is referred to herein, it is to be understood that such disclosure is non-limiting, and alternative preparations of comestible hemp seed hulls are also disclosed.

[0073] As used herein, the term "HiVeg," "BSD HiVeg media," or "HiVeg media" refers to a bacterial growth media containing a combination of plant peptones, yeast extracts and salt. Alternative bacterial growth media are known or commercially available, and can be used in place of HiVeg for the Examples disclosed herein.

[0074] As used herein, the term "about" or "approximately" means within an acceptable error range for the particular value as determined by one of ordinary skill in the art, which will depend in part on how the value is measured or determined, e.g., the limitations of the measurement system. For example, "about" can mean within 1 or more than 1 standard deviations, per the practice in the art. Alternatively, "about" can mean a range of up to 20%, up to 10%, up to 5%, and up to 1% of a given value. Alternatively, particularly with respect to biological systems or processes, the term can mean within an order of magnitude, within 5-fold, and within 2-fold, of a value. Where particular values are described in the application and claims, unless otherwise stated the term "about" meaning within an acceptable error range for the particular value should be assumed.

[0075] As used herein, the term "nutritionally acceptable additive" or "excipient" means a material, composition or vehicle, such as a liquid or solid filler, diluent, excipient, manufacturing aid (e.g., lubricant, talc magnesium, calcium or zinc stearate, or steric acid), or solvent encapsulating material, involved in carrying or transporting the subject compound from one organ, or portion of the body, to another organ, or portion of the body. Each nutritionally acceptable additive or excipient should be compatible with the other ingredients of the food, composition, or formulation and not injurious to the subject. Some examples of materials that can serve as nutritionally acceptable additives or excipients include: (1) sugars, such as lactose, glucose and sucrose; (2) starches, such ascorn starch and potato starch; (3) a cellulose not present in the plant mass or a cellulose additional to any cellulose present in the plant mass, and its derivatives; (4) powdered tragacanth; (5) malt; (6) gelatin; (7) talc; (8) excipients, such as cocoa butter and waxes;(9) oils, such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, com oil and soybean oil; (10) glycols, such as propylene glycol; (11) polyols, such as glycerin, sorbitol, mannitol and polyethylene glycol; (12) esters, such as ethyl oleate and ethyl laurate; (13) agar; (14) buffering agents, such as magnesium hydroxide and aluminum hydroxide; (15) alginic acid; (16) pyrogen-free water; (17) isotonic saline; (18) Ringer's solution; (19) ethyl alcohol; (20) pH buffered solutions; (21) polyesters, polycarbonates and / or polyanhydrides; and (22) other non-toxic compatible substances employed in conventional formulations or food products.

[0076] In some aspects, compositions, formulations, or comestible products described herein comprise N-trans-caffeoyltyramine (NCT) and / or N-trans-feruloyltyramine (NFT).

[0077] As used herein, "N-trans-caffeoyltyramine" ("NCT") means the compound having the following structure:

[0078] As used herein, "N-trans-feruloyltyramine" ("NFT") means the compound having the following structure:

[0079] As used herein, "N-cis-caffeoyltyramine" means the compound having the following structure:

[0080] As used herein, "N-cis-feruloyltyramine" means the compound having the following structure:

[0081] As used herein, the term "CFU / g" means colony-forming unit per gram. A colonyforming unit is where a colony of microbes grow on a petri dish, from one single microbe.

[0082] As used herein, the term “total aerobic plate count” is an indicator of bacterial populations on a sample.

[0083] As used herein, the term “substantially devoid” refers to a composition where a minor component of interest, e.g., Escherichia coli or Salmonella spp., is either not present or is present at a level at or below the minimum threshold. The desirable minimum threshold for a minor component of interest may vary according to the nature of the component.

[0084] As used herein, the term “total coliforms” is the total of a group of bacteria that are commonly found in the environment, including in soil, water, and the intestines of humans and animals.

[0085] The terms "treat," "treating," and "treatment," as used herein, refer to any type of intervention or process performed on, or administering an active agent (e.g., any of the compositions such as the comestible compositions provided herein) to a subject with the objective of reversing, alleviating, ameliorating, inhibiting, preventing, or slowing down the progression, development, severity or recurrence of a symptom, complication,condition or biochemical indicia associated with a disease, disorder, or condition described herein (e.g., a gastrointestinal disease or disorder). As used herein, the terms "treat," "treating," and "treatment" refer to the administration of an effective dose or effective dosage. As further described herein, in some aspects, treating a disease, disorder, or condition described herein comprises reducing or preventing an incidence of an infection in a subject suffering from the disease or disorder.

[0086] The terms "prevent," "preventing," and "prevention," as used herein, refer to partially or completely delaying onset of a disease, disorder, or condition described herein; partially or completely delaying onset of one or more symptoms, features, or clinical manifestations of a disease, disorder, or condition described herein; partially or completely delaying onset of one or more symptoms, features, or manifestations of a disease, disorder, or condition described herein; partially or completely delaying progression of a disease, disorder, or condition described herein; and / or decreasing the risk of developing pathology associated with a disease, disorder, or condition described herein, e.g., a gastrointestinal disease or disorder.

[0087] As used herein, the term "probiotic" refers to one or more live microorganisms, such as bacteria or yeast, or a composition comprising same, useful as a dietary supplement to help with digestion and / or normal bowel function.

[0088] As used herein, the term "prebiotic" refers to a substance, such as fiber or a carbohydrate, or a composition comprising same, that is indigestible in whole or in part and that when consumed (such as in a food) promotes the growth of beneficial bacteria in the digestive tract.

[0089] As used herein, the term "synbiotic" refers to a composition comprising a prebiotic component and a probiotic component.

[0090] The term "microbiota" refers to the ecological community of microorganisms that occur (sustainably or transiently) in and on an animal subject, typically a mammal such as a human, including eukaryotes, archaea, bacteria, and viruses (including bacterial viruses i.e., phage).

[0091] The term "microbiome" refers to the genetic content of the communities of microbes that live in and on the human body, both sustainably and transiently, including eukaryotes, archaea, bacteria, and viruses (including bacterial viruses (i.e., phage)),wherein "genetic content" includes genomic DNA, RNA such as ribosomal RNA, the epigenome, plasmids, and all other types of genetic information.

[0092] The term "dysbiosis" refers to a state of the microbiota of the GI tract or other body area in a subject, including mucosal or skin surfaces in which the normal diversity and / or function of the ecological network is disrupted. This unhealthy state can be due to a decrease in diversity, the overgrowth of one or more pathogens or pathobionts, symbiotic organisms able to cause disease only when certain genetic and / or environmental conditions are present in a subject, or the shift to an ecological microbial network that no longer provides an essential function to the host subject, and therefore no longer promotes health. As described herein, in some aspects, a disease or disorder that can be treated or prevented with the present disclosure can be associated with a dysbiosis.

[0093] As referred to herein, bacteria of a given species are disclosed by name or by a characteristic 16S rDNA sequence. Bacteria that share >98.7% average nucleotide identity across the entire 16S or a variable region of the 16S rDNA, e.g., a V4 region, are considered to be the same species (see, e.g., Stackebrandt, E. and Ebers, J. (2006) Taxonomic Parameters Revisited: Tarnished Gold Standards. Microbiology Today, 33, 152-155.). Identification of and reference to bacterial species described herein can be found throughout the present disclosure, including the Figures / Drawings and Sequence Listing. Where a taxonomic name is used or referenced for a specific bacterium, it is understood that the bacterium may have previously had a different taxonomic name(s) and that one of skill in the art would have resources available to identify and associate previous taxonomic names with those described herein, as used in the art, or both. Such resources include, but are not limited to, Bergey's Manual of Systematics of Archea and Bacteria (1st Ed.); Bergey's Manual of Systematic Bacteriology (2nd Ed.); the online version available at onlinelibrary .wiley. com / doi / book / 10.1002 / 9781118960608; and the National Center for Biotechnology Information (NCBI) database available online at ncbi.nlm.nih.gov / taxonomy.

[0094] As used herein, the term "inhibit" (or grammatical variants thereof) comprises both complete inhibition and partial inhibition.

[0095] As used herein, the term "plurality of bacteria" refer to a combination of two or more bacteria, except where otherwise specified. A "combination" of two or more bacteria includes the physical co-existence of the two bacteria, either in the same materialor product or in physically connected products, as well as the temporal co-administration or co-localization of the two bacteria. In some aspects, the plurality of bacteria comprises two or more strains of the same species of bacteria. In some aspects, the plurality of bacteria comprises two or more bacteria of different species. In some aspects, the plurality of bacteria comprises three or more bacteria comprising two bacteria that are different strains of the same species, and a third bacteria that is a different species than the two bacteria that are different strains of the same species.

[0096] As used herein, the term "plurality of yeast" refer to a combination of two or more yeast, except where otherwise specified. A "combination" of two or more yeast includes the physical co-existence of the two yeast, either in the same material or product or in physically connected products, as well as the temporal co-administration or colocalization of the two yeast. In some aspects, the plurality of yeast comprises two or more strains of the same species of yeast. In some aspects, the plurality of yeast comprises two or more yeast of different species. In some aspects, the plurality of yeast comprises three or more yeast comprising two yeast that are different strains of the same species, and a third yeast that is a different species than the two yeast that are different strains of the same species.

[0097] The percent identity between two sequences is a function of the number of identical positions shared by the sequences (i.e., % homology = # of identical positions / total # of positions x 100), taking into account the number of gaps, and the length of each gap, which need to be introduced for optimal alignment of the two sequences. The comparison of sequences and determination of percent identity between two sequences can be accomplished using a mathematical algorithm, as described in the non-limiting examples below.

[0098] The percent identity between two nucleotide sequences can be determined using the GAP program in the GCG software package (available at worldwideweb.gcg.com), using a NWSgapdna.CMP matrix and a gap weight of 40, 50, 60, 70, or 80 and a length weight of 1, 2, 3, 4, 5, or 6. The percent identity between two nucleotide or amino acid sequences can also be determined using the algorithm of E. Meyers and W. Miller (CABIOS, 4: 11-17 (1989)) which has been incorporated into the ALIGN program (version 2.0), using a PAM120 weight residue table, a gap length penalty of 12 and a gap penalty of 4. In addition, the percent identity between two amino acid sequences can bedetermined using the Needleman and Wunsch (J. Mol. Biol. (48):444-453 (1970)) algorithm which has been incorporated into the GAP program in the GCG software package (available at worldwideweb.gcg.com), using either a Blossum 62 matrix or a PAM250 matrix, and a gap weight of 16, 14, 12, 10, 8, 6, or 4 and a length weight of 1, 2, 3, 4, 5, or 6.

[0099] The sequences described herein can further be used as a "query sequence" to perform a search against public databases to, for example, identify related sequences. Such searches can be performed using the NBLAST and XBLAST programs (version 2.0) of Altschul, et al. (1990) J. Mol. Biol. 215:403-10. BLAST nucleotide searches can be performed with the NBLAST program, score = 100, wordlength = 12 to obtain nucleotide sequences homologous to the nucleic acid molecules described herein. BLAST protein searches can be performed with the XBLAST program, score = 50, wordlength = 3 to obtain amino acid sequences homologous to the protein molecules described herein. To obtain gapped alignments for comparison purposes, Gapped BLAST can be utilized as described in Altschul et al., (1997) Nucleic Acids Res. 25(17):3389-3402. When utilizing BLAST and Gapped BLAST programs, the default parameters of the respective programs (e.g., XBLAST and NBLAST) can be used. See worldwideweb.ncbi.nlm.nih.gov. Other methods of determining identity that are known in the art can be used.

[0100] As used herein, "lignan" or "lignans" are compounds possessing a 2,3- dibenzylbutane structure and exist as minor constituents of many plants, where they may form the building blocks for the formation of lignin (as distinguished from lignan) found in the plant cell wall.

[0101] As used herein, "lignin" is an amorphous polymer related to cellulose that provides rigidity and together with cellulose forms the woody cell walls of plants and the cementing material between them. Lignin content, composition and structure can be altered using genetic modification. (See, e.g., Liu, Q. et al. 2018. Lignins: Biosynthesis and Biological Functions in Plants. Int. J. Mol. Sci. 19(335): 1-16. doi: 10.3390 / ijmsl9020335).

[0102] As used herein, "cellulose" is a polysaccharide (CeHioCh) of glucose units that constitutes an important component of plant cell walls, occurs naturally in such fibrous products as hemp or psyllium, and is a component of dietary fiber.

[0103] As used herein, "hemicellulose" is any of various plant polysaccharides less complex than cellulose and hydrolyzable to monosaccharides and other products. Hemicelluloses include polysaccharides in plant cell walls that have P-( l ->4)-l inked backbones with an equatorial configuration. Hemicelluloses include xyloglucans, xylans, mannans and glucomannans, and P-(l- 3,l- 4)-glucans.

[0104] As used herein, “inulin” is a soluble dietary fiber found in more than 36,000 plant species as a reserve polysaccharide. Primary sources of inulin, include for example, Jerusalem artichoke, chicory, onion, garlic, barley, and dahlia, among which Jerusalem artichoke tubers and chicory roots are often used as raw materials for inulin production in the food industry.

[0105] As used herein, the terms "ug" and "uM" are used interchangeably with "pg" and "pM," respectively.

[0106] As used herein, a “Good Source” of fiber is defined as the characteristic of a composition of containing about 10 to 19 percent of the recommended daily intake or the daily recommended value of fiber. 9 C.F.R. § 317.354(c)(1). In some aspects, a composition containing a Good Source of fiber provides about 2.5, 2.6, 2.7, 2.8, 2.9, 3.0, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, 4.0, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, or 4.9 grams of fiber, or about 2.5 to 4.9 grams.

[0107] As used herein, a “High” amount of fiber is defined as the characteristic of a composition of containing about 20 percent of the recommended daily intake or the daily recommended value of fiber. 9 C.F.R. § 317.354(b)(1). In some aspects, a composition containing a High amount of fiber provides about 5 grams of fiber or more.

[0108] Where an aspect is disclosed herein, its negation is also disclosed. For example, the disclosure "in some aspects, the plurality of bacteria comprises L. rhamnosus" is also intended to disclose "in some aspects, the plurality of bacteria does not comprise L. rhamnosus."

[0109] Where compositions comprising a "plant mass" and a "plurality of bacteria, yeast, or both" (e.g., a "synbiotic" composition) are disclosed herein, such disclosures can refer to compositions comprising the plant mass without the plurality of bacteria, yeast, or both (e.g., a "prebiotic" composition). For example, disclosure of a synbiotic composition also discloses a corresponding prebiotic composition containing no bacteria, yeast, or both, or substantially no bacteria, yeast, or both. Conversely, where compositions comprising aplant mass (e.g., a prebiotic composition) are disclosed, such disclosures can refer to compositions comprising the plant mass and a plurality of bacteria, yeast, or both (e.g., a synbiotic composition). For example, disclosure of a prebiotic composition also discloses a corresponding synbiotic composition containing a useful amount of one or more bacterial entities, one or more yeast entities, or both. A skilled artisan will understand that a beneficial composition comprising a plant mass can be combined with a plurality of bacteria, yeast, or both to provide a beneficial composition comprising the plant mass and the plurality of bacteria, yeast, or both (e.g., a synbiotic composition).Compositions

[0110] In some aspects, the present disclosure provides a composition comprising a plant mass. In some aspects, the plant mass comprises a hemp hull fiber. In some aspects, the plant mass comprises a hemp hull fiber powder. In some aspects, the composition is a prebiotic composition.[OHl] In some aspects, the present disclosure provides a composition comprising a plurality of bacteria, yeast, or both and a plant mass. In some aspects, the plant mass comprises a hemp hull fiber. In some aspects, the composition is a synbiotic composition. In some aspects, the present disclosure provides a composition comprising a plurality of bacteria, yeast, or both and a plant mass comprising a cellulose, a hemicellulose, a lignan, a lignin, or a combination thereof. In some aspects, the composition comprises a plurality of bacteria, yeast, or both and a plant mass comprising a cellulose. In some aspects, the composition comprises a plurality of bacteria, yeast, or both and a plant mass comprising a hemicellulose. In some aspects, the composition comprises a plurality of bacteria, yeast, or both and a plant mass comprising a lignan. In some aspects, the composition comprises a plurality of bacteria, yeast, or both and a plant mass comprising a lignin.

[0112] In some aspects, the composition comprises N-trans-caffeoyltyramine (NCT) and / or N-trans-feruloyltyramine (NFT). In some aspects, the composition comprises N- trans-caffeoyltyramine (NCT). In some aspects, the composition comprises N-trans- feruloyltyramine (NFT). In some aspects, the composition comprises N-cis- caffeoyltyramine and / or N-cis-feruloyltyramine. In some aspects, the composition comprises N-cis-caffeoyltyramine. In some aspects, the composition comprises N-cis- feruloyltyramine. In some aspects, the compositions comprising N-trans-caffeoyltyramine(NCT) and / or N-trans-feruloyltyramine (NFT) described above further comprise a plurality of bacteria, yeast, or both.

[0113] Cellulose, hemicellulose, lignin, and lignan are provided as exemplary useful plant components. However, it is intended that references to compositions disclosed herein, or uses and methods thereof, also include compositions, uses, and methods with additional plant components instead of (and / or including) a cellulose, a hemicellulose, a lignan and / or a lignin, such as a metabolite of a cellulose, a hemicellulose, a lignan, or a lignin. Further, metabolites produced by a composition comprising a plurality of bacteria, yeast, or both and a hemp hull fiber are described in Table 1. In some aspects, the compositions described herein are capable of producing one or more metabolites listed in Table 1. In some aspects, the compositions described herein further comprise one or more metabolites listed in Table 1.Features of the plurality of bacteria or the plurality of yeast

[0114] In some aspects, the plurality of bacteria comprises only one species or strain of bacteria. In some aspects, the plurality of bacteria comprises two or more species or strains of bacteria. In some aspects, the plurality of bacteria comprises 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25 species or strains of bacteria. In some aspects, the plurality of bacteria comprises more than one strain of the same species of bacteria, and more than one species of bacteria. Thus, in some aspects, the compositions described herein comprise a plurality of bacteria comprising only one species or strain of bacteria and a plant mass comprising a cellulose, a hemicellulose, a lignan, a lignin, or a combination thereof. And, in some aspects, the compositions described herein comprise a plurality of bacteria comprising two or more species or strains of bacteria and a plant mass comprising a cellulose, a hemicellulose, a lignan, a lignin, or a combination thereof. In some aspects, the compositions described herein comprise a plurality of bacteria comprising only one species or strain of bacteria and a hemp hull fiber. In some aspects, the compositions described herein comprise a plurality of bacteria comprising two or more species or strains of bacteria and a hemp hull fiber.

[0115] In some aspects, the plurality of bacteria comprises bacteria comprising a 16S rDNA sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97.0%, 97.1%, 97.2%, 97.3%, 97.4%, 97.5%, 97.6%, 97.7%, 97.8%, 97.9%, 98.0%, 98.1%, 98.2%, 98.3%, 98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.0%,99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 99.99% identity to a 16S rDNA sequence of a bacteria disclosed herein, or to a 16S rDNA sequence disclosed herein. In some aspects, the plurality of bacteria comprises bacteria comprising a 16S rDNA sequence preferably having at least 97.0%, 97.1%, 97.2%, 97.3%, 97.4%, 97.5%, 97.6%, 97.7%, 97.8%, 97.9%, 98.0%, 98.1%, 98.2%, 98.3%, 98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.0%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 99.99% identity to a 16S rDNA sequence of a bacteria disclosed herein, or to a 16S rDNA sequence disclosed herein.

[0116] In some aspects, the plurality of bacteria comprises bacteria of the genus Lacticaseibacillus (formerly part the genus Lactobacillus). In some aspects, the plurality of bacteria comprises bacteria selected from Lacticaseibacillus rhamnosus.Lacticaseibacillus casei, Lacticaseibacillus paracasei, or a combination thereof. In some aspects, the plurality of bacteria comprises bacteria of the family Lactobacillaceae .

[0117] In some aspects, the plurality of bacteria does not comprise Blautia producta, Eggerthella lenta, or both. In some aspects, the plurality of bacteria does not comprise a Blautia species. In some aspects, the plurality of bacteria does not comprise an Eggerthella species.

[0118] In some aspects, the plurality of bacteria comprises Eggerthella lenta strain ATCC 43055, Eggerthella lenta strain ATC 25559, or both. In some aspects, the plurality of bacteria does not comprise Eggerthe Ila lenta strain ATCC 43055, Eggerthella lenta strain ATC 25559, or both.

[0119] In some aspects, the plurality of bacteria comprises Lacticaseibacillus rhamnosus strain ATCC 7469. In some aspects, the plurality of bacteria does not comprise Lacticaseibacillus rhamnosus strain ATCC 7469.

[0120] In some aspects, the plurality of bacteria comprises Lacticaseibacillus casei strain ATCC 393. In some aspects, the plurality of bacteria does not comprise Lacticaseibacillus casei strain ATCC 393.

[0121] In some aspects, the plurality of bacteria comprises Lacticaseibacillus paracasei strain ATCC 11578. In some aspects, the plurality of bacteria does not comprise Lacticaseibacillus paracasei strain ATCC 11578.

[0122] In some aspects, the plurality of bacteria comprises Blautia producta strain ATCC 27340. In some aspects, the plurality of bacteria does not comprise Blautia producta strain ATCC 27340.

[0123] In some aspects, the plurality of bacteria comprises bacteria of the genus Enterococcus, Lactobacillus, Bifidobacterium, Lactococcus, Streptococcus, or a combination thereof. In some aspects, the plurality of bacteria comprises bacteria selected from Enterococcus faecalis, Lactobacillus reuteri, Bifidobacterium animalis, Bifidobacterium longum, Lactobacillus helveticus, Lactococcus lactis, Lactobacillus acidophilus, Streptococcus thermophiles, or a combination thereof. In some aspects, the plurality of bacteria comprises bacteria selected from Enterococcus faecalis BAA-2820, Lactobacillus reuteri BAA-2837, Bifidobacterium animalis subsp. Lactis BAA-2848, Bifidobacterium longum BAA-999, Lactobacillus helveticus BAA-2840, Lactococcus lactis subsp. Lactis ATCC 19435, Lactobacillus acidophilus BAA-2832, Streptococcus thermophilus BAA- 19258, or a combination thereof. In some aspects, the plurality of bacteria described herein does not comprise Blautia producta, Eggerthella lenta, or both. In some aspects, the plurality of bacteria described herein does not comprise Blautia species. In some aspects, the plurality of bacteria described herein does not comprise an Eggerthella species.

[0124] In some aspects, the plurality of bacteria comprises spores. In some aspects, the plurality of bacteria comprises vegetative cells. In some aspects, the plurality of bacteria comprises spores and vegetative cells.

[0125] In some aspects, the plurality of bacteria comprises a polynucleotide encoding an enzyme that catabolizes a cellulose, a hemicellulose, a lignan, a lignin, or a combination thereof.

[0126] In some aspects, the plurality of bacteria comprises recombinant bacteria genetically engineered to comprise the polynucleotide encoding an enzyme that degrades the cellulose, the hemicellulose, the lignan, or the lignin. In some aspects, the plurality of bacteria comprises recombinant bacteria and non-recombinant bacteria. In some aspects, the plurality of bacteria does not comprise recombinant bacteria.

[0127] In some aspects, the plurality of bacteria comprises a bacterial species or strain capable of catabolizing a cellulose, a hemicellulose, a lignan, or a lignin.

[0128] In some aspects, the plurality of yeast comprises only one species or strain of yeast. In some aspects, the plurality of yeast comprises two or more species or strains of yeast. In some aspects, the plurality of yeast comprises 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25 species or strains of yeast. In some aspects, the plurality of yeast comprises more than one strain of the same species of yeast, and more than one species of yeast. Thus, in some aspects, the compositions described herein comprise a plurality of yeast comprising only one species or strain of yeast and a plant mass comprising a cellulose, a hemicellulose, a lignan, a lignin, or a combination thereof. And, in some aspects, the compositions described herein comprise a plurality of yeast comprising two or more species or strains of yeast and a plant mass comprising a cellulose, a hemicellulose, a lignan, a lignin, or a combination thereof. In some aspects, the compositions described herein comprise a plurality of yeast comprising only one species or strain of yeast and a hemp hull fiber. In some aspects, the compositions described herein comprise a plurality of yeast comprising two or more species or strains of yeast and a hemp hull fiber.

[0129] In some aspects, the plurality of yeast comprises yeast of the genus Saccharomyces. In some aspects, the plurality of yeast comprises Saccharomyces cerevisiae. In some aspects, the plurality of yeast comprises Saccharomyces cerevisiae MYA-797.

[0130] In some aspects of the plurality of bacteria and the plurality of yeast described above, the plurality of bacteria comprises bacteria of the genus Enterococcus, Lactobacillus, Bifidobacterium, Lactococcus, Streptococcus, or a combination thereof, and the plurality of yeast comprises yeast of the genus Saccharomyces. In some aspects of the plurality of bacteria and the plurality of yeast described above, the plurality of bacteria comprises bacteria of the genus Lacticaseibacillus (formerly part of the genus Lactobacillus'), Enterococcus, Lactobacillus, Bifidobacterium, Lactococcus, Streptococcus, or a combination thereof, and the plurality of yeast comprises yeast of the genus Saccharomyces. In some aspects, the plurality of bacteria comprises bacteria selected from Enterococcus faecalis, Lactobacillus reuteri, Bifidobacterium animalis, Bifidobacterium longum, Lactobacillus helveticus, Lactococcus lactis, Lactobacillus acidophilus, Streptococcus thermophiles, or a combination thereof, and the plurality of yeast comprises Saccharomyces cerevisiae. In some aspects, the plurality of bacteriacomprises bacteria selected from Lacticaseibacillus rhamnosus, Lacticaseibacillus casei, Lacticaseibacillus paracasei, Enterococcus faecalis, Lactobacillus reuteri, Bifidobacterium animalis, Bifidobacterium longum, Lactobacillus helveticus, Lactococcus lactis, Lactobacillus acidophilus, Streptococcus thermophiles, or a combination thereof, and the plurality of yeast comprises Saccharomyces cerevisiae. In some aspects, the plurality of bacteria comprises bacteria selected from Enterococcus faecalis BAA-2820, Lactobacillus reuteri BAA-2837, Bifidobacterium animalis subsp. Lactis BAA-2848, Bifidobacterium longum BAA-999, Lactobacillus helveticus BAA- 2840, Lactococcus lactis subsp. Lactis ATCC 19435, Lactobacillus acidophilus BAA- 2832, Streptococcus thermophilus BAA-19258, or a combination thereof, and the plurality of yeast comprises Saccharomyces cerevisiae MYA-797. In some aspects, the plurality of bacteria comprises bacteria selected from Eggerthella lenta strain ATCC 43055, Eggerthella lenta strain ATC 25559, Lacticaseibacillus rhamnosus strain ATCC 7469, Lacticaseibacillus casei strain ATCC 393, Lacticaseibacillus paracasei strain ATCC 11578, Blautia producta strain ATCC 27340, Enterococcus faecalis BAA-2820, Lactobacillus reuteri BAA-2837, Bifidobacterium animalis subsp. Lactis BAA-2848, Bifidobacterium longum BAA-999, Lactobacillus helveticus BAA-2840, Lactococcus lactis subsp. Lactis ATCC 19435, Lactobacillus acidophilus BAA-2832, Streptococcus thermophilus BAA-19258, or a combination thereof, and the plurality of yeast comprises Saccharomyces cerevisiae MYA-797. In some aspects of the plurality of bacteria and plurality of yeast described above, the plurality of bacteria does not comprise Blautia producta, Eggerthella lenta, or both.Features of the plant mass

[0131] In some aspects, the plant mass comprises a hemp hull fiber. In some aspects, the plant mass comprises a hemp hull fiber powder, and wherein the hemp hull fiber powder is prepared by a method comprising a step of processing a hemp seed hull.

[0132] In some aspects, the plant mass comprises less than 2% wt / v N-trans- caffeoyltyramine (NCT) and / or N-trans-feruloyltyramine (NFT). In some aspects, the plant mass comprises less than 2.0%, 1.9%, 1.8%, 1.7%, 1.6%, 1.5%, 1.4%, 1.3%, 1.2%, 1.1%, 1.0%, 0.9%, 0.8%, 0.7%, 0.6%, 0.5%, 0.4%, 0.3%, 0.2%, or 0.1% wt / v N-trans- caffeoyltyramine (NCT) and / or N-trans-feruloyltyramine (NFT).

[0133] In some aspects, the plant mass is derived from a plant that produces N-trans- caffeoyltyramine (NCT) and / or N-trans-feruloyltyramine (NFT).

[0134] In some aspects, the plant mass is derived from a cannabis species. In some aspects, the plant mass is derived from a Cannabis sativa species. In some aspects, the plant mass is derived from a hemp species. In some aspects, the plant mass is derived from Plantago species. In some aspects, the plant mass is derived from Plantago ovata (Plantago psyllium).

[0135] In some aspects, the plant mass comprises a substance derived from seed hulls or husks. In some aspects, the seed hulls are derived from a Cannabis sativa species. In some aspects, the seed hulls are derived from a hemp species. In some aspects, the plant mass comprises a hemp hull fiber.

[0136] In some aspects, the plant mass is an extruded plant mass. In some aspects, the plant mass is not an extruded plant mass.

[0137] In some aspects, the plant mass comprises less than 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, 0.9%, 0.8%, 0.7%, 0.6%, 0.5%, 0.4%, 0.3%, 0.2%, 0.1%, 0.09%, 0.08%, 0.07%, 0.06%, 0.05%, 0.04%, 0.03%, 0.02%, or 0.01% w / w of inulin. In some aspects, the plant mass does not comprise a detectable amount of inulin. In some aspects, the hemp hull fiber comprises less than 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, 0.9%, 0.8%, 0.7%, 0.6%, 0.5%, 0.4%, 0.3%, 0.2%, 0.1%, 0.09%, 0.08%, 0.07%, 0.06%, 0.05%, 0.04%, 0.03%, 0.02%, or 0.01% w / w of inulin. In some aspects, the hemp hull fiber does not comprise a detectable amount of inulin.

[0138] In some aspects, the husks are derived from a Plantago species.

[0139] In some aspects, a composition disclosed herein comprises material derived from the husk of Plantago ovata (Plantago psyllium).

[0140] In some aspects, a composition disclosed herein comprises about 0.25 mg / mL to about 50 mg / mL of the plant mass, such as hemp hull fiber. In some aspects, a composition disclosed herein comprises about 0.01 mg / mL to about 100 mg / mL of the plant mass, such as hemp hull fiber. In some aspects, the composition comprises about 0.01, 0.05, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, or 100 mg / mL of the plant mass, such as hemp hull fiber. In some aspects, the composition comprises less than about 0.01, 0.05, 0.15,0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, or 100 mg / mL of the plant mass, such as hemp hull fiber. In some aspects, the composition comprises more than about 0.01, 0.05, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, or 100 mg / mL of the plant mass, such as hemp hull fiber.Comestible compositions

[0141] In some aspects, the present disclosure provides a comestible composition comprising a composition disclosed herein and a nutritionally acceptable additive. In some aspects, the nutritionally acceptable additive comprises a vitamin, mineral, or essential nutrient (e.g., essential amino acid, essential fat). In some aspects, the nutritionally acceptable additive comprises biotin, vitamin Bi, thiamin, thiamin pyrophosphate, vitamin B2, riboflavin, flavin mononucleoride, flavin adenine dinucleotide, pyridoxine hydrochloride, thiamin mononitrate, folic acid, vitamin B3, niacin, nicotinic acid, nicotinamide, niacinamide, nicotinamide adenine dinucleotide, tryptophan, biotin, pantothenic acid, vitamin Be, vitamin B12, cobalamin, methylcobalamin, deoxyadenosylcobalamin, cyanocobalamin, calcium pantothenate, pantothenic acid, vitamin C, ascorbic acid, vitamin A, retinol, retinal, retinoic acid, betacarotene, vitamin D, vitamin D3, calciferol, cholecalciferol, dihydroxy vitamin D, 1,25- dihydroxycholecalciferol, 7-dehyrdocholesteroli choline, vitamin E, vitamin E acetate, vitamin K, menadione, menaquinone, phylloquinone, naphthoquinone, or a combination thereof. In some aspects, the nutritionally acceptable additive comprises phosphorus, potassium, sulfur, sodium, docusate sodium, chloride, manganese, magnesium, magnesium stearate, magnesium carbonate, magnesium oxide, magnesium hydroxide, magnesium sulfate, copper, cupric sulfate, iodide, boron, zinc, zinc oxide, chromium, molybdenum, iron, carbonyl iron, ferric iron, ferrous fumarate, polysaccharide iron, fluoride, selenium, molybdenum, calcium phosphate or acetate, potassium phosphate, magnesium sulfate or oxide, sodium chloride, potassium chloride or acetate, ferric orthophosphate, alpha- tocopheryl acetate, zinc sulfate or oxide, copper gluconate, chromium chloride or picolonate, potassium iodide, sodium selenate, sodium molybdate, phylloquinone, cyanocobalamin, sodium selenite, copper sulfate, inositol, potassiumiodide, cobalt, or a combination thereof. In some aspects, the nutritionally acceptable additive is a caloric sweetener. In some aspects, the nutritionally acceptable additive comprises glucose, fructose, dextrose, lactose, galactose, saccharides, sucrose, maltose, a sugar alcohol (such as sorbitol, mannitol, or xylitol), a syrup (such as maltitol, corn syrup, rice syrup, or high fructose corn syrup) or a combination thereof. In some aspects, the nutritionally acceptable additive comprises a non-caloric sweetener, e.g., sucralose, saccharine, cyclamates, aspartamine, aspartame, acesulfame K, sorbitol, and mixtures thereof. In some aspects, the nutritionally acceptable additive comprises a food ingredient. In some aspects, the nutritionally acceptable additive is provided in solid form. In some aspects, the nutritionally acceptable additive is provided in liquid form.

[0142] In some aspects, the nutritionally acceptable additive comprises a prebiotic additive. In some aspects, the prebiotic additive comprises a fructo-oligosaccharide. In some aspects, the prebiotic additive comprises a galacto-oligosaccharide. In some aspects, the prebiotic additive comprises a trans-galacto-oligosaccharide. Other suitable prebiotic additives are known in the art. See, e.g., Davani-Davari, D. et al. 2019. Prebiotics: Definition, Types, Sources, Mechanisms, and Clinical Applications. Foods. 8, 92. doi: 10.3390 / foods8030092.

[0143] In some aspects, the prebiotic additive comprises a prebiotic substance not present in the plant mass, such as hemp hull fiber. In some aspects, the prebiotic additive comprises a prebiotic substance present in the plant mass, such as hemp hull fiber.

[0144] In some aspects, the nutritionally acceptable additive comprises a postbiotic. In some aspects, the postbiotic comprises an inanimate microbe. In some aspects, the postbiotic comprises cell fragments. In some aspects, the postbiotic comprises dead bacteria. In some aspects, the postbiotic comprises a bacterial metabolite. Suitable postbiotic additives are known in the art. See, e.g., Vinderola, G. et al. 2022. The Concept of Postbiotics. Foods. 11, 1077.

[0145] In some aspects, the bacterial metabolite is one or more of: (a) N-trans- feruloyltyramine; (b) N-trans-caffeoyltyramine; (c) (E)-9-Octadecenoic acid methyl ester; (d) Oleic acid; (e) (9Z,12E)-15,16-Dihydroxyoctadeca-9,12-dienoic acid; (f) 12- Hydroxystearic acid; (g) Ricinoleic acid; (h) 13 -Oxooctadecanoic acid, (i) 8,9- Dihydroxy-5Z,l lZ,14Z-eicosatrienoic acid; (j) 9, 10-Epoxy stearic acid; (k) (5E,9E)- Farnesylacetone; (1) Borrelidin; (m) Gamma-Linolenic acid; (n) Isopropyl (9Z,12Z)-9,12-octadecadienoate; (o) Medroxyprogesterone; (p) Palmitoylethanolamide; (q) (12Z,15Z)- 7,9,10-Trihydroxyoctadeca-12,15-dienoic acid; (r) 4-Amino-3 -[(3 -hydroxy- 10- methylundecanoyl)amino]-4-oxobutanoic acid; (s) (9Z,12Z)-7,8,16-trihydroxyoctadeca- 9,12-dienoic acid; (t) l l,12-Dihydroxy-5Z,8Z,14Z-eicosatrienoic acid; (u) (9E)-N- Hydroxy-9-octadecenamide; (v) (1R,2R,3S,1'R)-Nepetalinic acid; (w) Simvastatin d'methyl ether; (x) Fucosterol; (y) Stearoylethanolamide; (z) Paprazine; (aa) cannabidiol; (bb) [(6E,10E)-12-(2,6-dihydroxy-4-methylphenyl)-2,6,10-trimethyl-4-oxododeca-6,10- dien-5-yl] acetate; (cc) Suberic acid; (dd) (E)-4-Hydroxy-2-dodecenedioic acid; (ee) Cannabidiolic acid; (ff) methyl (10E,12Z)-9-oxooctadeca-10,12-di enoate; (gg) Sinapaldehyde; (hh) 17-Hydroxyheptadecanoic acid; (ii) (3-Hydroxy-2-octadeca-9,12- di enoyloxypropyl) 2-(trimethylazaniumyl)ethyl phosphate; (jj) (S)-3-(4-Hydroxyphenyl)- 2-hydroxypropionic acid; (kk) Radiclonic acid; (11) Succinic acid; or (mm) Laetisaric acid.

[0146] In some aspects, a composition disclosed herein is a synbiotic composition comprising a bacteria, yeast, or both as described herein and a prebiotic. In some aspects, the synbiotic further comprises a postbiotic.

[0147] In some aspects, the nutritionally acceptable additive comprises a flavoring agent, an odor masking agent, a coloring agent, a mouthfeel agent, or a combination thereof. In some aspects, the flavoring agent comprises a flavored extract, a volatile oil, cocoa or chocolate flavoring, a peanut butter flavoring, cookie crumbs, vanilla, any commercially available flavoring, or a combination thereof. In some aspects, the flavoring agent is pure anise extract, imitation banana extract, imitation cherry extract, chocolate extract, pure lemon extract, pure orange extract, pure peppermint extract, imitation pineapple extract, imitation rum extract, imitation strawberry extract, or vanilla extract, a volatile oil (such as balm oil, bay oil, bergamot oil, cedarwood oil, cherry oil, cinnamon oil, clove oil, or peppermint oil), peanut butter, chocolate flavoring, vanilla cookie crumb, butterscotch, toffee, or a combination thereof. In some aspects, the coloring agent is a food dye.

[0148] In some aspects, the comestible composition is in liquid form. In some aspects, the comestible composition comprises a solution, slurry, or emulsion. In some aspects, the comestible composition comprises a beverage suitable for human consumption. In some aspects, the comestible composition comprises a Ready-to-Drink (RTD) beverage.

[0149] In some aspects, the comestible composition is in solid form. In some aspects, the comestible composition comprises one or more capsules or tablets. In some aspects, the comestible composition comprises a food product. In some aspects, the comestible composition comprises a crisp (e.g., a protein crisp). In some aspects, the comestible composition comprises a powder, e.g., a compressed or non-compressed powder. In some aspects, the composition is a dry solid. In some aspects, the comestible composition comprises a Ready -to-Mix (RTM) powder.

[0150] In some aspects, the comestible composition is a dietary supplement.

[0151] In some aspects, the comestible composition is suitable for animal consumption.In some aspects, the comestible composition is suitable for veterinary use.Method of making comestible composition

[0152] The present disclosure provides methods for making a comestible composition disclosed herein.

[0153] In some aspects, making the comestible composition comprises cooking the processed hemp hull fiber in a horizontal cooker with continuous paddle agitation. In some aspects, making the comestible composition comprises one or more of solvent extraction, supercritical fluid extraction, refining oil content, bleaching, deodorizing oil content, methods for application of heat other than cooking, application of light, exposure to oxygen, increase or decrease in pH, or aging. In some aspects, the step of cooking comprises roasting.

[0154] In some aspects, the hemp hull fiber is subjected to a size reduction step to form a powder. In some aspects, the size reduction step is milling.

[0155] In some aspects, processing the hemp hull fiber comprises, for each processing step other than those involving heating, maintaining about the same temperature throughout the processing step. In some aspects, each processing step other than those involving heating is performed at the same temperature. In some aspects, each processing step other than those involving heating is performed at a different temperature. In some aspects, two or more processing steps other than those involving heating are performed at the same temperature.

[0156] In some aspects, an anti-caking agent is included in the comestible composition.

[0157] In some aspects, the comestible composition is cooled prior to storage.

[0158] In some aspects, the comestible composition is processed in accordance with current Good Manufacturing Practice (cGMP).

[0159] In some aspects, the comestible composition is mixed with a nutritionally acceptable additive.

[0160] In some aspects, the processed hemp hull fiber is mixed with a nutritionally acceptable additive, thereby providing the comestible composition described herein.

[0161] In some aspects, the comestible composition is subjected to a step of certifying it as halal, kosher, organic, upcycled certified, and / or non-GMO project verified.Additional comestible compositions

[0162] The present disclosure provides comestible compositions disclosed herein in the form of a food, a beverage, or an additive to a food and / or a beverage.

[0163] In some aspects, the comestible composition is in liquid form. In some aspects, the comestible composition comprises a solution, slurry, or emulsion. In some aspects, the comestible composition comprises a beverage suitable for human consumption. In some aspects the beverage can be in ready-to-mix form. In some aspects the beverage can be in ready-to-drink form. In some aspects, the comestible composition is a beverage or beverage base, including, but not limited to, a non-milk-based meal-replacement nutritional beverage, a non-milk-based protein beverage, or a non-milk-based nutritional beverage, including powder forms. In some aspects, the beverage or beverage base comprises about 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2.0, 2.1, 2.2, 2.3, 2.4, 2.5,2.6, 2.7, 2.8, 2.9, 3.0, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, 4.0, 4.1, 4.2, 4.3, 4.4, 4.5,4.6, 4.7, 4.8, 4.9, 5.0, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, 6.0, 6.1, 6.2, 6.3, 6.4, 6.5,6.6, 6.7, 6.8, 6.9, 7.0, 7.1, 7.2, 7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.9, 8.0, 8.1, 8.2, 8.3, 8.4, 8.5,8.6, 8.7, 8.8, 8.9, 9.0, 9.1, 9.2, 9.3, 9.4, 9.5, 9.6, 9.7, 9.8, 9.9, 10.0, 10.5, 11.0, 11.5, 12.0,12.5, 13.0, 13.5, 14.0, 14.5, 15.0, 15.5, 16.0, 16.5, 17.0, 17.5, 18.0, 18.5, 19.0, 19.5, 20.0, or more g hemp hull fiber per serving. In some aspects, the beverage or beverage base comprises about 9.3 or 9.4 g hemp hull fiber per serving. In some aspects, the amount of fiber per serving (on a dietary fiber basis) provided by the hemp hull fiber in the beverage or beverage base comprises about 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2.0, 2.1,2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3.0, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, 4.0, 4.1,4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9, 5.0, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, 6.0, 6.1,6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, 7.0, 7.1, 7.2, 7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.9, 8.0, 8.1,8.2, 8.3, 8.4, 8.5, 8.6, 8.7, 8.8, 8.9, 9.0, 9.1, 9.2, 9.3, 9.4, 9.5, 9.6, 9.7, 9.8, 9.9, 10.0, 10.5, 11.0, 11.5, 12.0, 12.5, 13.0, 13.5, 14.0, 14.5, 15.0, 15.5, 16.0, 16.5, 17.0, 17.5, 18.0, 18.5, 19.0, 19.5, 20.0, or more g per serving. In some aspects, the amount of fiber per serving (on a dietary fiber basis) provided by the hemp hull fiberin the beverage or beverage base comprises between about 1.0-10.0, 1.0-9.0, 1.0-8.0, 1.0-7.0, 1.0-6.0, 1.0-5.0, 1.0-4.0, 1.0- 3.0, 1.0-2.0, 2.0-10.0, 2.0-9.0, 2.0-8.0, 2.0-7.0, 2.0-6.0, 2.0-5.0, 2.0-4.0, 2.0-3.0, 3.0-10.0, 3.0-9.0, 3.0-8.0, 3.0-7.0, 3.0-6.0, 3.0-5.0, 3.0-4.0, 4.0-10.0, 4.0-9.0, 4.0-8.0, 4.0-7.0, 4.0- 6.0, 4.0-5.0, 5.0-10.0, 5.0-9.0, 5.0-8.0, 5.0-7.0, 5.0-6.0, 6.0-10.0, 6.0-9.0, 6.0-8.0, 6.0-7.0, 7.0-10.0, 7.0-9.0, 7.0-8.0, 8.0-10.0, 8.0-9.0, or 9.0-10.0 g per serving. In some aspects, the amount of fiber per serving (on a dietary fiber basis) provided by the hemp hull fiber in the beverage or beverage base comprises between about 5.6-7.4 g per serving.

[0164] In some aspects, the comestible composition is a milk product, including, but not limited to, a milk-based meal-replacement nutritional beverage, a milk-based protein beverage, or a milk-based nutritional beverage, including powder forms. In some aspects, the milk product comprises about 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2.0, 2.1,2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3.0, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, 4.0, 4.1,4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9, 5.0, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, 6.0, 6.1,6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, 7.0, 7.1, 7.2, 7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.9, 8.0, 8.1,8.2, 8.3, 8.4, 8.5, 8.6, 8.7, 8.8, 8.9, 9.0, 9.1, 9.2, 9.3, 9.4, 9.5, 9.6, 9.7, 9.8, 9.9, 10.0, 10.5,11.0, 11.5, 12.0, 12.5, 13.0, 13.5, 14.0, 14.5, 15.0, 15.5, 16.0, 16.5, 17.0, 17.5, 18.0, 18.5, 19.0, 19.5, 20.0, or more g hemp hull fiber per serving. In some aspects, the milk product comprises about 9.3 or 9.4 g hemp hull fiber per serving. In some aspects, the amount of fiber per serving (on a dietary fiber basis) provided by the hemp hull fiber in the milk product comprises about 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2.0, 2.1, 2.2, 2.3, 2.4,2.5, 2.6, 2.7, 2.8, 2.9, 3.0, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, 4.0, 4.1, 4.2, 4.3, 4.4,4.5, 4.6, 4.7, 4.8, 4.9, 5.0, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, 6.0, 6.1, 6.2, 6.3, 6.4,6.5, 6.6, 6.7, 6.8, 6.9, 7.0, 7.1, 7.2, 7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.9, 8.0, 8.1, 8.2, 8.3, 8.4,8.5, 8.6, 8.7, 8.8, 8.9, 9.0, 9.1, 9.2, 9.3, 9.4, 9.5, 9.6, 9.7, 9.8, 9.9, 10.0, 10.5, 11.0, 11.5,12.0, 12.5, 13.0, 13.5, 14.0, 14.5, 15.0, 15.5, 16.0, 16.5, 17.0, 17.5, 18.0, 18.5, 19.0, 19.5, 20.0, or more g per serving. In some aspects, the amount of fiber per serving (on a dietary fiber basis) provided by the hemp hull fiber in the milk product comprises between about 1.0-10.0, 1.0-9.0, 1.0-8.0, 1.0-7.0, 1.0-6.0, 1.0-5.0, 1.0-4.0, 1.0-3.0, 1.0-2.0, 2.0-10.0, 2.0-9.0, 2.0-8.0, 2.0-7.0, 2.0-6.0, 2.0-5.0, 2.0-4.0, 2.0-3.0, 3.0-10.0, 3.0-9.0, 3.0-8.0, 3.0-7.0, 3.0-6.0, 3.0-5.0, 3.0-4.0, 4.0-10.0, 4.0-9.0, 4.0-8.0, 4.0-7.0, 4.0-6.0, 4.0-5.0, 5.0-10.0, 5.0- 9.0, 5.0-8.0, 5.0-7.0, 5.0-6.0, 6.0-10.0, 6.0-9.0, 6.0-8.0, 6.0-7.0, 7.0-10.0, 7.0-9.0, 7.0-8.0, 8.0-10.0, 8.0-9.0, or 9.0-10.0 g per serving. In some aspects, the amount of fiber per serving (on a dietary fiber basis) provided by the hemp hull fiber in the milk product base comprises between about 5.6-7.4 g per serving.

[0165] In some aspects, the comestible composition is a processed fruit or fruit juice, including, but not limited to, a fruit drink (excluding 100% juice and nectars), a vegetable drink (excluding 100% juice and nectars), or a fruit smoothie, including concentrates and powder forms. In some aspects, the processed fruit or fruit juice comprises about 1.0, 1.1,1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2.0, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3.0, 3.1,3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, 4.0, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9, 5.0, 5.1,5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, 6.0, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, 7.0, 7.1,7.2, 7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.9, 8.0, 8.1, 8.2, 8.3, 8.4, 8.5, 8.6, 8.7, 8.8, 8.9, 9.0, 9.1,9.2, 9.3, 9.4, 9.5, 9.6, 9.7, 9.8, 9.9, 10.0, 10.5, 11.0, 11.5, 12.0, 12.5, 13.0, 13.5, 14.0,14.5, 15.0, 15.5, 16.0, 16.5, 17.0, 17.5, 18.0, 18.5, 19.0, 19.5, 20.0, or more g hemp hull fiber per serving. In some aspects, the processed fruit or fruit juice comprises about 4.6 or 4.7 g hemp hull fiber per serving. In some aspects, the amount of fiber per serving (on a dietary fiber basis) provided by the hemp hull fiber in the processed fruit or fruit juice comprises about 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2.0, 2.1, 2.2, 2.3, 2.4, 2.5,2.6, 2.7, 2.8, 2.9, 3.0, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, 4.0, 4.1, 4.2, 4.3, 4.4, 4.5,4.6, 4.7, 4.8, 4.9, 5.0, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, 6.0, 6.1, 6.2, 6.3, 6.4, 6.5,6.6, 6.7, 6.8, 6.9, 7.0, 7.1, 7.2, 7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.9, 8.0, 8.1, 8.2, 8.3, 8.4, 8.5,8.6, 8.7, 8.8, 8.9, 9.0, 9.1, 9.2, 9.3, 9.4, 9.5, 9.6, 9.7, 9.8, 9.9, 10.0, 10.5, 11.0, 11.5, 12.0,12.5, 13.0, 13.5, 14.0, 14.5, 15.0, 15.5, 16.0, 16.5, 17.0, 17.5, 18.0, 18.5, 19.0, 19.5, 20.0, or more g per serving. In some aspects, the amount of fiber per serving (on a dietary fiber basis) provided by the hemp hull fiber in the processed fruit or fruit juice comprises between about 1.0-10.0, 1.0-9.0, 1.0-8.0, 1.0-7.0, 1.0-6.0, 1.0-5.0, 1.0-4.0, 1.0-3.0, 1.0- 2.0, 2.0-10.0, 2.0-9.0, 2.0-8.0, 2.0-7.0, 2.0-6.0, 2.0-5.0, 2.0-4.0, 2.0-3.0, 3.0-10.0, 3.0-9.0, 3.0-8.0, 3.0-7.0, 3.0-6.0, 3.0-5.0, 3.0-4.0, 4.0-10.0, 4.0-9.0, 4.0-8.0, 4.0-7.0, 4.0-6.0, 4.0- 5.0, 5.0-10.0, 5.0-9.0, 5.0-8.0, 5.0-7.0, 5.0-6.0, 6.0-10.0, 6.0-9.0, 6.0-8.0, 6.0-7.0, 7.0- 10.0, 7.0-9.0, 7.0-8.0, 8.0-10.0, 8.0-9.0, or 9.0-10.0 g per serving. In some aspects, theamount of fiber per serving (on a dietary fiber basis) provided by the hemp hull fiber in the processed fruit or fruit juice comprises between about 2.8-4.0 g per serving.

[0166] In some aspects, the comestible composition is a processed vegetable or vegetable juice, including, but not limited to, a vegetable smoothie, including concentrates and powder forms. In some aspects, the processed vegetable or vegetable juice comprises about 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2.0, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8,2.9, 3.0, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, 4.0, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8,4.9, 5.0, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, 6.0, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8,6.9, 7.0, 7.1, 7.2, 7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.9, 8.0, 8.1, 8.2, 8.3, 8.4, 8.5, 8.6, 8.7, 8.8,8.9, 9.0, 9.1, 9.2, 9.3, 9.4, 9.5, 9.6, 9.7, 9.8, 9.9, 10.0, 10.5, 11.0, 11.5, 12.0, 12.5, 13.0,13.5, 14.0, 14.5, 15.0, 15.5, 16.0, 16.5, 17.0, 17.5, 18.0, 18.5, 19.0, 19.5, 20.0, or more g hemp hull fiber per serving. In some aspects, the processed vegetable or vegetable juice comprises about 4.6 or 4.7 g hemp hull fiber per serving. In some aspects, the amount of fiber per serving (on a dietary fiber basis) provided by the hemp hull fiber in the processed vegetable or vegetable juice comprises about 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6,1.7, 1.8, 1.9, 2.0, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3.0, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6,3.7, 3.8, 3.9, 4.0, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9, 5.0, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6,5.7, 5.8, 5.9, 6.0, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, 7.0, 7.1, 7.2, 7.3, 7.4, 7.5, 7.6,7.7, 7.8, 7.9, 8.0, 8.1, 8.2, 8.3, 8.4, 8.5, 8.6, 8.7, 8.8, 8.9, 9.0, 9.1, 9.2, 9.3, 9.4, 9.5, 9.6,9.7, 9.8, 9.9, 10.0, 10.5, 11.0, 11.5, 12.0, 12.5, 13.0, 13.5, 14.0, 14.5, 15.0, 15.5, 16.0,16.5, 17.0, 17.5, 18.0, 18.5, 19.0, 19.5, 20.0, or more g per serving. In some aspects, the amount of fiber per serving (on a dietary fiber basis) provided by the hemp hull fiber in the processed vegetable or vegetable juice comprises between about 1.0-10.0, 1.0-9.0,1.0-8.0, 1.0-7.0, 1.0-6.0, 1.0-5.0, 1.0-4.0, 1.0-3.0, 1.0-2.0, 2.0-10.0, 2.0-9.0, 2.0-8.0, 2.0- 7.0, 2.0-6.0, 2.0-5.0, 2.0-4.0, 2.0-3.0, 3.0-10.0, 3.0-9.0, 3.0-8.0, 3.0-7.0, 3.0-6.0, 3.0-5.0, 3.0-4.0, 4.0-10.0, 4.0-9.0, 4.0-8.0, 4.0-7.0, 4.0-6.0, 4.0-5.0, 5.0-10.0, 5.0-9.0, 5.0-8.0, 5.0- 7.0, 5.0-6.0, 6.0-10.0, 6.0-9.0, 6.0-8.0, 6.0-7.0, 7.0-10.0, 7.0-9.0, 7.0-8.0, 8.0-10.0, 8.0- 9.0, or 9.0-10.0 g per serving. In some aspects, the amount of fiber per serving (on a dietary fiber basis) provided by the hemp hull fiber in the processed vegetable or vegetable juice comprises between about 2.8-4.0 g per serving.

[0167] In some aspects, the comestible composition comprises a food product. In some aspects, the comestible composition is a baked good or baking mix, including, but notlimited to, whole-grain and high-fiber bread or rolls (optionally excluding sweet-type breads or rolls), cookies, brownies, muffins, quick breads, pancakes, or waffles. In some aspects, the baked good or baking mix comprises about 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6,1.7, 1.8, 1.9, 2.0, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3.0, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6,3.7, 3.8, 3.9, 4.0, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9, 5.0, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6,5.7, 5.8, 5.9, 6.0, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, 7.0, 7.1, 7.2, 7.3, 7.4, 7.5, 7.6,7.7, 7.8, 7.9, 8.0, 8.1, 8.2, 8.3, 8.4, 8.5, 8.6, 8.7, 8.8, 8.9, 9.0, 9.1, 9.2, 9.3, 9.4, 9.5, 9.6,9.7, 9.8, 9.9, 10.0, 10.5, 11.0, 11.5, 12.0, 12.5, 13.0, 13.5, 14.0, 14.5, 15.0, 15.5, 16.0,16.5, 17.0, 17.5, 18.0, 18.5, 19.0, 19.5, 20.0, or more g hemp hull fiber per serving. In some aspects, the baked good or baking mix comprises about 4.6 or 4.7 g hemp hull fiber per serving. In some aspects, the amount of fiber per serving (on a dietary fiber basis) provided by the hemp hull fiber in the baked good or baking mix comprises about 1.0,1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2.0, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3.0,3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, 4.0, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9, 5.0,5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, 6.0, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, 7.0,7.1, 7.2, 7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.9, 8.0, 8.1, 8.2, 8.3, 8.4, 8.5, 8.6, 8.7, 8.8, 8.9, 9.0,9.1, 9.2, 9.3, 9.4, 9.5, 9.6, 9.7, 9.8, 9.9, 10.0, 10.5, 11.0, 11.5, 12.0, 12.5, 13.0, 13.5, 14.0,14.5, 15.0, 15.5, 16.0, 16.5, 17.0, 17.5, 18.0, 18.5, 19.0, 19.5, 20.0, or more g per serving. In some aspects, the amount of fiber per serving (on a dietary fiber basis) provided by the hemp hull fiber in the baked good or baking mix comprises between about 1.0-10.0, 1.0- 9.0, 1.0-8.0, 1.0-7.0, 1.0-6.0, 1.0-5.0, 1.0-4.0, 1.0-3.0, 1.0-2.0, 2.0-10.0, 2.0-9.0, 2.0-8.0, 2.0-7.0, 2.0-6.0, 2.0-5.0, 2.0-4.0, 2.0-3.0, 3.0-10.0, 3.0-9.0, 3.0-8.0, 3.0-7.0, 3.0-6.0, 3.0- 5.0, 3.0-4.0, 4.0-10.0, 4.0-9.0, 4.0-8.0, 4.0-7.0, 4.0-6.0, 4.0-5.0, 5.0-10.0, 5.0-9.0, 5.0-8.0, 5.0-7.0, 5.0-6.0, 6.0-10.0, 6.0-9.0, 6.0-8.0, 6.0-7.0, 7.0-10.0, 7.0-9.0, 7.0-8.0, 8.0-10.0,8.0-9.0, or 9.0-10.0 g per serving. In some aspects, the amount of fiber per serving (on a dietary fiber basis) provided by the hemp hull fiber in the baked good or baking mix comprises between about 2.8-4.0 g per serving.

[0168] In some aspects, the comestible composition is a breakfast cereal, including, but not limited to, low-sugar (<21%), ready-to-eat breakfast cereals, puffed cereals, high-fiber cereals, biscuit-type cereals, or granola. In some aspects, the breakfast cereal comprises about 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2.0, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3.0, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, 4.0, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8,4.9, 5.0, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, 6.0, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8,6.9, 7.0, 7.1, 7.2, 7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.9, 8.0, 8.1, 8.2, 8.3, 8.4, 8.5, 8.6, 8.7, 8.8,8.9, 9.0, 9.1, 9.2, 9.3, 9.4, 9.5, 9.6, 9.7, 9.8, 9.9, 10.0, 10.5, 11.0, 11.5, 12.0, 12.5, 13.0,13.5, 14.0, 14.5, 15.0, 15.5, 16.0, 16.5, 17.0, 17.5, 18.0, 18.5, 19.0, 19.5, 20.0, or more g hemp hull fiber per serving. In some aspects, the breakfast cereal comprises about 4.6 or 4.7 g hemp hull fiber per serving. In some aspects, the amount of fiber per serving (on a dietary fiber basis) provided by the hemp hull fiber in the breakfast cereal comprises about 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2.0, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8,2.9, 3.0, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, 4.0, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8,4.9, 5.0, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, 6.0, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8,6.9, 7.0, 7.1, 7.2, 7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.9, 8.0, 8.1, 8.2, 8.3, 8.4, 8.5, 8.6, 8.7, 8.8,8.9, 9.0, 9.1, 9.2, 9.3, 9.4, 9.5, 9.6, 9.7, 9.8, 9.9, 10.0, 10.5, 11.0, 11.5, 12.0, 12.5, 13.0,13.5, 14.0, 14.5, 15.0, 15.5, 16.0, 16.5, 17.0, 17.5, 18.0, 18.5, 19.0, 19.5, 20.0, or more g per serving. In some aspects, the amount of fiber per serving (on a dietary fiber basis) provided by the hemp hull fiber in the breakfast cereal comprises between about 1.0-10.0,I.0-9.0, 1.0-8.0, 1.0-7.0, 1.0-6.0, 1.0-5.0, 1.0-4.0, 1.0-3.0, 1.0-2.0, 2.0-10.0, 2.0-9.0, 2.0- 8.0, 2.0-7.0, 2.0-6.0, 2.0-5.0, 2.0-4.0, 2.0-3.0, 3.0-10.0, 3.0-9.0, 3.0-8.0, 3.0-7.0, 3.0-6.0, 3.0-5.0, 3.0-4.0, 4.0-10.0, 4.0-9.0, 4.0-8.0, 4.0-7.0, 4.0-6.0, 4.0-5.0, 5.0-10.0, 5.0-9.0, 5.0- 8.0, 5.0-7.0, 5.0-6.0, 6.0-10.0, 6.0-9.0, 6.0-8.0, 6.0-7.0, 7.0-10.0, 7.0-9.0, 7.0-8.0, 8.0- 10.0, 8.0-9.0, or 9.0-10.0 g per serving. In some aspects, the amount of fiber per serving (on a dietary fiber basis) provided by the hemp hull fiber in the breakfast cereal comprises between about 2.8-4.0 g per serving.

[0169] In some aspects, the comestible composition is a grain product or pasta, including, but not limited to, a nutritional bar (e.g., a grain-based nutritional bar, a non-grain based nutritional bar, a protein nutritional bar, an energy nutritional bar, a meal replacement bar, or a combination thereof), a cereal bar, or a granola bar. In some aspects, the grain product or pasta comprises about 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2.0, 2.1, 2.2,2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3.0, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, 4.0, 4.1, 4.2,4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9, 5.0, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, 6.0, 6.1, 6.2,6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, 7.0, 7.1, 7.2, 7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.9, 8.0, 8.1, 8.2,8.3, 8.4, 8.5, 8.6, 8.7, 8.8, 8.9, 9.0, 9.1, 9.2, 9.3, 9.4, 9.5, 9.6, 9.7, 9.8, 9.9, 10.0, 10.5,I I.0, 11.5, 12.0, 12.5, 13.0, 13.5, 14.0, 14.5, 15.0, 15.5, 16.0, 16.5, 17.0, 17.5, 18.0, 18.5,19.0, 19.5, 20.0, or more g hemp hull fiber per serving. In some aspects, the grain product or pasta, such as a nutritional bar, comprises about 9.3 or 9.4 g hemp hull fiber per serving. In some aspects, the grain product or pasta, such as a cereal bar or granola bar, comprises about 4.6 or 4.7 g hemp hull fiber per serving. In some aspects, the amount of fiber per serving (on a dietary fiber basis) provided by the hemp hull fiber in the grain product or pasta comprises about 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2.0, 2.1, 2.2,2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3.0, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, 4.0, 4.1, 4.2,4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9, 5.0, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, 6.0, 6.1, 6.2,6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, 7.0, 7.1, 7.2, 7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.9, 8.0, 8.1, 8.2,8.3, 8.4, 8.5, 8.6, 8.7, 8.8, 8.9, 9.0, 9.1, 9.2, 9.3, 9.4, 9.5, 9.6, 9.7, 9.8, 9.9, 10.0, 10.5,11.0, 11.5, 12.0, 12.5, 13.0, 13.5, 14.0, 14.5, 15.0, 15.5, 16.0, 16.5, 17.0, 17.5, 18.0, 18.5, 19.0, 19.5, 20.0, or more g per serving. In some aspects, the amount of fiber per serving (on a dietary fiber basis) provided by the hemp hull fiber in the grain product or pasta comprises between about 1.0-10.0, 1.0-9.0, 1.0-8.0, 1.0-7.0, 1.0-6.0, 1.0-5.0, 1.0-4.0, 1.0- 3.0, 1.0-2.0, 2.0-10.0, 2.0-9.0, 2.0-8.0, 2.0-7.0, 2.0-6.0, 2.0-5.0, 2.0-4.0, 2.0-3.0, 3.0-10.0, 3.0-9.0, 3.0-8.0, 3.0-7.0, 3.0-6.0, 3.0-5.0, 3.0-4.0, 4.0-10.0, 4.0-9.0, 4.0-8.0, 4.0-7.0, 4.0- 6.0, 4.0-5.0, 5.0-10.0, 5.0-9.0, 5.0-8.0, 5.0-7.0, 5.0-6.0, 6.0-10.0, 6.0-9.0, 6.0-8.0, 6.0-7.0, 7.0-10.0, 7.0-9.0, 7.0-8.0, 8.0-10.0, 8.0-9.0, or 9.0-10.0 g per serving. In some aspects, the amount of fiber per serving (on a dietary fiber basis) provided by the hemp hull fiber in the grain product or pasta, such as a nutritional bar, comprises between about 5.6-7.9 g per serving. In some aspects, the amount of fiber per serving (on a dietary fiber basis) provided by the hemp hull fiber in the grain product or pasta, such as a cereal bar or granola bar, comprises between about 2.8-4.0 g per serving.

[0170] In some aspects, the comestible composition is a snack food, including, but not limited to, extruded snacks. In some aspects, the snack food comprises about 1.0, 1.1, 1.2,1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2.0, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3.0, 3.1, 3.2,3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, 4.0, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9, 5.0, 5.1, 5.2,5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, 6.0, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, 7.0, 7.1, 7.2,7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.9, 8.0, 8.1, 8.2, 8.3, 8.4, 8.5, 8.6, 8.7, 8.8, 8.9, 9.0, 9.1, 9.2,9.3, 9.4, 9.5, 9.6, 9.7, 9.8, 9.9, 10.0, 10.5, 11.0, 11.5, 12.0, 12.5, 13.0, 13.5, 14.0, 14.5, 15.0, 15.5, 16.0, 16.5, 17.0, 17.5, 18.0, 18.5, 19.0, 19.5, 20.0, or more g hemp hull fiber per serving. In some aspects, the snack food comprises about 9.3 or 9.4 g hemp hull fiberper serving. In some aspects, the snack food comprises about 4.6 or 4.7 g hemp hull fiber per serving. In some aspects, the amount of fiber per serving (on a dietary fiber basis) provided by the hemp hull fiber in the snack food comprises about 1.0, 1.1, 1.2, 1.3, 1.4,1.5, 1.6, 1.7, 1.8, 1.9, 2.0, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3.0, 3.1, 3.2, 3.3, 3.4,3.5, 3.6, 3.7, 3.8, 3.9, 4.0, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9, 5.0, 5.1, 5.2, 5.3, 5.4,5.5, 5.6, 5.7, 5.8, 5.9, 6.0, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, 7.0, 7.1, 7.2, 7.3, 7.4,7.5, 7.6, 7.7, 7.8, 7.9, 8.0, 8.1, 8.2, 8.3, 8.4, 8.5, 8.6, 8.7, 8.8, 8.9, 9.0, 9.1, 9.2, 9.3, 9.4,9.5, 9.6, 9.7, 9.8, 9.9, 10.0, 10.5, 11.0, 11.5, 12.0, 12.5, 13.0, 13.5, 14.0, 14.5, 15.0, 15.5, 16.0, 16.5, 17.0, 17.5, 18.0, 18.5, 19.0, 19.5, 20.0, or more g per serving. In some aspects, the amount of fiber per serving (on a dietary fiber basis) provided by the hemp hull fiber in the snack food comprises between about 1.0-10.0, 1.0-9.0, 1.0-8.0, 1.0-7.0, 1.0-6.0,1.0-5.0, 1.0-4.0, 1.0-3.0, 1.0-2.0, 2.0-10.0, 2.0-9.0, 2.0-8.0, 2.0-7.0, 2.0-6.0, 2.0-5.0, 2.0- 4.0, 2.0-3.0, 3.0-10.0, 3.0-9.0, 3.0-8.0, 3.0-7.0, 3.0-6.0, 3.0-5.0, 3.0-4.0, 4.0-10.0, 4.0-9.0, 4.0-8.0, 4.0-7.0, 4.0-6.0, 4.0-5.0, 5.0-10.0, 5.0-9.0, 5.0-8.0, 5.0-7.0, 5.0-6.0, 6.0-10.0, 6.0- 9.0, 6.0-8.0, 6.0-7.0, 7.0-10.0, 7.0-9.0, 7.0-8.0, 8.0-10.0, 8.0-9.0, or 9.0-10.0 g per serving. In some aspects, the amount of fiber per serving (on a dietary fiber basis) provided by the hemp hull fiber in the snack food comprises between about 5.6-7.9 g per serving.Pharmaceutical compositions

[0171] In some aspects, the present disclosure provides a pharmaceutical composition comprising a composition disclosed herein and a pharmaceutically acceptable excipient. Non-limiting examples of pharmacologically acceptable excipients can be found in, e.g., Pharmaceutical Dosage Forms and Drug Delivery Systems (Howard C. Ansel et al., eds., Lippincott Williams & Wilkins Publishers, 7th ed. 1999); Remington: The Science and Practice of Pharmacy (Alfonso R. Gennaro ed., Lippincott, Williams & Wilkins, 20th ed. 2000); Goodman & Gilman's The Pharmacological Basis of Therapeutics (Joel G. Hardman et al., eds., McGraw-Hill Professional, 10th ed. 2001); and Handbook of Pharmaceutical Excipients (Raymond C. Rowe et al., APhA Publications, 4th edition 2003), each of which is hereby incorporated by reference in its entirety.

[0172] In some aspects, a composition of the present disclosure is prepared by a method comprising one or more steps disclosed in, or comprises a composition disclosed in, any one of the following references, each of which are incorporated by reference herein:W02019140052A1, WO2021096813A1, W02019140046A1, WO2023141427A1, WO2022081567A1, WO2021081222A1, WO2021119020A1.

[0173] In some aspects, the pharmaceutical composition comprises a nutritionally acceptable additive disclosed herein.

[0174] In some aspects, the pharmaceutical composition comprises a prebiotic additive.

[0175] In some aspects, the prebiotic additive comprises a prebiotic substance not present in the plant mass, such as hemp hull fiber. In some aspects, the prebiotic additive comprises a prebiotic substance present in the plant mass, such as hemp hull fiber.

[0176] In some aspects, the pharmaceutically acceptable excipient comprises a flavoring agent, an odor masking agent, a coloring agent, a mouthfeel agent, or a combination thereof.

[0177] In some aspects, the present disclosure provides an oral dosage form comprising a composition described herein.

[0178] In some aspects, the oral dosage form comprises about 1 gram to about 4.9 grams of fiber. In some aspects, the oral dosage form comprises a “Good Source” level of fiber or about 2.8 grams of fiber. In some aspects, the oral dosage form comprises about 2.5 grams to about 4.9 grams of fiber.

[0179] In some aspects, the oral dosage form comprises about 5 grams of fiber or more. In some aspects, the oral dosage form comprises a “High” level of fiber. In some aspects, the oral dosage form comprises about 5 grams to about 10 grams of fiber. In some aspects, the oral dosage form comprises about 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, or 10 grams of fiber. In some aspects, the oral dosage form comprises more than about 10 grams of fiber.

[0180] In some aspects, the pharmaceutical composition or oral dosage form comprises a solution, slurry, suspension, or emulsion.

[0181] In some aspects, the pharmaceutical composition or oral dosage form comprises a solid dosage form. In some aspects, the solid dosage form comprises a powder, a capsule, or a tablet. In some aspects, the solid dosage form comprises two or more capsules or tablets.

[0182] In some aspects, the pharmaceutical composition or oral dosage form is a dietary supplement.

[0183] In some aspects, the oral dosage form is formulated for delivery to the intestines. In some aspects, the oral dosage form comprises an enteric polymer.

[0184] In some aspects, the pharmaceutical composition comprises a rectal dosage form. In some aspects, the rectal dosage form is a suppository. In some aspects, the rectal dosage form is a liquid.Methods of preparing compositions

[0185] In some aspects, the present disclosure provides a method of preparing a plant mass. In some aspects, the plant mass comprises a hemp hull fiber. In some aspects, the plant mass comprises a hemp hull fiber powder. In some aspects, the hemp hull fiber powder is prepared by a method comprising a step of processing a hemp seed hull.

[0186] In some aspects, the plant mass is an extruded plant mass. Methods of extrusion are known in the art, and include, without limitation, those disclosed in, e.g., WO2023172920A2, which is incorporated by reference in its entirety. In some aspects, the plant mass is not an extruded plant mass.

[0187] In some aspects, the present disclosure provides a method of preparing a composition disclosed herein, for example, a comestible composition disclosed herein, a pharmaceutical composition disclosed herein, or an oral dosage form disclosed herein, comprising a step of pre-treating the plurality of bacteria. In some aspects, the step of pretreating comprises heat-treating the plurality of bacteria. In some aspects, the step of pretreating comprises ethanol -treating the plurality of bacteria. In some aspects, the step of pre-treating comprises increasing or decreasing the pH of a growth media comprising a bacterial species or strain of the plurality of bacteria. In some aspects, the step of pretreating comprises increasing or decreasing the salt content of a growth media comprising a bacterial species or strain of the plurality of bacteria. In some aspects, the step of pretreating comprises inducing sporulation in a bacterial species or strain of the plurality of bacteria.

[0188] In some aspects, the step of pre-treating comprises growing one or more bacteria of the plurality of bacteria in a growth media composition comprising a plant mass disclosed herein. In some aspects, the growth media composition is prepared by a method comprising a step of sterilizing the growth media composition. In some aspects, the step of sterilizing the growth media composition comprises autoclaving the growth mediacomposition. In some aspects, one or more bacteria of the plurality of bacteria is grown to logarithmic growth phase, then combined with the growth media composition.

[0189] In some aspects, the step of pre-treating comprises germinating a plurality of spores.

[0190] In some aspects, the step of pre-treating comprises growing a plurality of bacterial cells to logarithmic phase. In some aspects, the step of pre-treating comprises growing a plurality of bacterial cells to beyond logarithmic phase.

[0191] In some aspects, the present disclosure provides a method of preparing a composition disclosed herein, for example, a comestible composition disclosed herein, a pharmaceutical composition disclosed herein, or an oral dosage form disclosed herein, comprising a step of pre-treating the plurality of yeast. In some aspects, the step of pretreating comprises increasing or decreasing the pH of a growth media comprising a yeast species or strain of the plurality of yeast. In some aspects, the step of pre-treating comprises increasing or decreasing the salt content of a growth media comprising a yeast species or strain of the plurality of yeast.

[0192] In some aspects, the step of pre-treating comprises growing one or more yeast of the plurality of yeast in a growth media composition comprising a plant mass disclosed herein. In some aspects, the growth media composition is prepared by a method comprising a step of sterilizing the growth media composition. In some aspects, the step of sterilizing the growth media composition comprises autoclaving the growth media composition. In some aspects, one or more yeast of the plurality of yeast is grown to logarithmic growth phase, then combined with the growth media composition.

[0193] In some aspects, the present disclosure provides a method of preparing a composition disclosed herein comprising a step of preparing a plurality of bacteria, yeast, or both to be combined with a plant mass disclosed herein.

[0194] In some aspects, the present disclosure provides a method of preparing a plurality of bacteria, yeast, or both for coadministration with a plant mass disclosed herein. In some aspects, coadministration comprises administration of the plant mass before or after administration of the plurality of bacteria, yeast, or both. In some aspects, coadministration comprises contemporaneous administration of both the plant mass and the plurality of bacteria, yeast, or both.Methods of use

[0195] In some aspects, the present disclosure provides a method of treating or reducing the risk of a disease, disorder, dysbiosis, or condition, of improving gut epithelial barrier integrity, of increasing gut transepithelial electrical resistance (TEER), of reducing one or more symptoms of gastrointestinal discomfort, of reducing the risk of gastrointestinal discomfort, or of improving gastrointestinal comfort, or of increasing gut microbial diversity, comprising administering an effective amount of a composition disclosed herein, a comestible composition disclosed herein, a pharmaceutical composition disclosed herein, or an oral dosage form disclosed herein to a subject in need thereof.

[0196] In some aspects, the present disclosure provides a method of treating or reducing the risk of a disease, disorder, dysbiosis, or condition, or of improving gut epithelial barrier integrity, of increasing gut transepithelial electrical resistance (TEER), of reducing one or more symptoms of gastrointestinal discomfort, of reducing the risk of gastrointestinal discomfort, or of improving gastrointestinal comfort, or of increasing gut microbial diversity, comprising administering to a subject in need thereof an effective amount of a plurality of bacteria, yeast, or both, and a plant mass comprising a cellulose, a hemicellulose, a lignan, a lignin, or a combination thereof, wherein the plant mass and the plurality of bacteria, yeast, or both are not contained within the same dosage form.

[0197] In some aspects, the one or more symptoms of gastrointestinal discomfort is assessed by one or more of: Digestion Associated Quality of Life Questionnaire (DQLQ), PROMIS Belly Pain 5a, PROMIS GI Gas and Bloating 13a, and PROMIS Anxiety 4a.

[0198] In some aspects, the one or more symptoms of gastrointestinal discomfort is one or more of: abdominal pain, flatulence, bloating, and anxiety. In some aspects, the one or more symptoms of gastrointestinal discomfort is improved more than the level of improvement observed following administration of a mass of inulin equivalent to the mass of the plant mass, such as hemp hull fiber, administered to the subject. In some aspects, the risk of gastrointestinal discomfort is decreased more than the level of decrease observed following administration of a mass of inulin equivalent to the mass of the plant mass, such as hemp hull fiber, administered to the subject.

[0199] In some aspects, the risk of gastrointestinal comfort is improved more than the level of improvement observed following administration of a mass of inulin equivalent to the mass of the plant mass, such as hemp hull fiber, administered to the subject.

[0200] In some aspects, the present disclosure provides a method of increasing the abundance of target bacteria, yeast, or both in the gut of a subject in need thereof, comprising administering to the subject an effective amount of a plurality of bacteria, yeast, or both, and a plant mass comprising a cellulose, a hemicellulose, a lignan, a lignin, or a combination thereof. In some aspects, the target bacteria comprises one or more bacteria of the order Lactobacillales, the family Lactobacillaceae or the genus Lacticaseibacillus. In some aspects, the target bacteria comprises one or more bacteria of the genus Enterococcus, Lactobacillus, Bifidobacterium, Lactococcus, Streptococcus, Lacticaseibacillus, Blautia, or Egger thella. In some aspects, the target bacteria comprises Lacticaseibacillus casei, Lacticaseibacillus rhamnosus, Lacticaseibacillus paracasei, or a combination thereof. In some aspects, the target yeast comprises one or more yeast of the genus Saccharomyces. In some aspects, the present disclosure provides a method of increasing the abundance of Lactobacillaceae in the gut of a subject in need thereof, comprising administering to the subject an effective amount of a plurality of bacteria, yeast, or both, and a plant mass comprising a cellulose, a hemicellulose, a lignan, a lignin, or a combination thereof.

[0201] In some aspects, the plurality of bacteria, yeast, or both further comprises and / or the plant mass comprises N-trans-caffeoyltyramine (NCT) and / or N-trans- feruloyltyramine (NFT). In some aspects, the plurality of bacteria, yeast, or both further comprises and / or the plant mass comprises N-cis-caffeoyltyramine and / or N-cis- feruloyltyramine.

[0202] In some aspects, the disease or disorder is selected from Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH).

[0203] In some aspects, the disease or disorder is a gastrointestinal disease or disorder. In some aspects, the gastrointestinal disease or disorder is selected from irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), Crohn's disease (CD), ulcerative colitis (UC), celiac disease, necrotizing enterocolitis, indeterminate colitis, chronic colitis, HIV enteropathy, Helicobacter gastritis, NSAID-enteropathy / enteritis, pouchitis, discontinuous or patchy disease, ileal inflammation, extracolonic inflammation, granulomatous inflammation in response to ruptured crypts, aphthous ulcers, transmural inflammation, microscopic colitis, diverticulitis, diversion colitis, short bowel syndrome,GI mucositis, chemotherapy induced mucositis, radiation induced mucositis, and interstitial cystitis.

[0204] In some aspects, the abundance of Lactobacillaceae in the gut of the subject is increased following administration. In some aspects, the abundance of one or more bacteria of the genus Enterococcus, Lactobacillus, Bifidobacterium, Lactococcus, Streptococcus, Lacticaseibacillus, Blautia, or Eggerthella is increased following administration. In some aspects, the abundance of one or more yeast of the genus Saccharomyces is increased following administration.

[0205] In some aspects, the abundance of bacteria of the family Enterob acteriaceae in the gut of the subject is not increased following administration.

[0206] In some aspects, the concentration of a short-chain fatty acid in the gut of the subject is increased following administration. In some aspects, the short-chain fatty acid comprises acetic acid, propanoic acid, butyric acid, or a combination thereof.

[0207] In some aspects, the composition, the comestible composition, the pharmaceutical composition, or the oral dosage form is administered as two or more capsules daily. In some aspects, the oral dosage form is administered as 2, 3, 4, 5, 6, 7, 8, 9, or 10 capsules daily.Methods of treatment including diagnostic steps

[0208] In some aspects, a method disclosed herein comprising an administering step further comprises obtaining a fecal sample from the subject, determining the abundance of Lactobacillaceae present in the fecal sample from the subject, and administering the composition to the subject if the abundance of Lactobacillaceae present in the fecal sample from the subject is less than about 0.001%, 0.01%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 1.5%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 30%, 35%, 40%, 45%, or 50% relative to the total abundance of bacteria in the fecal sample. In some aspects, a method disclosed herein comprising an administering step further comprises obtaining a fecal sample from the subject, determining the abundance of one or more bacteria of the genus Enterococcus, Lactobacillus, Bifidobacterium, Lactococcus, Streptococcus, Lacticaseibacillus, Blautia, o Eggerthella and / or one or more yeast of the genus Saccharomyces present in the fecal sample from the subject, and administering the composition to the subject if the abundance of one or more bacteria ofthe genus Enterococcus, Lactobacillus, Bifidobacterium, Lactococcus, Streptococcus, Lacticaseibacillus, Blautia, or Eggerthella and / or one or more yeast of the genus Saccharomyces present in the fecal sample from the subject is less than about 0.001%, 0.01%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 1.5%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 30%, 35%, 40%, 45%, or 50% relative to the total abundance in the fecal sample.

[0209] In some aspects, a method disclosed herein comprising an administering step further comprises obtaining a fecal sample from the subject, determining the abundance of Lactobacillaceae present in the fecal sample from the subject, obtaining a fecal sample from a healthy donor, determining the abundance of Lactobacillaceae present in the fecal sample from the healthy donor, and administering the composition to the subject if the abundance of Lactobacillaceae present in the fecal sample is less than 10% relative to the abundance of Lactobacillaceae present in the fecal sample from the healthy donor. In some aspects, the composition is administered to the subject if the abundance of Lactobacillaceae present in the fecal sample is less than about 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, 0.9%, 0.8%, 0.7%, 0.6%, 0.5%, 0.4%, 0.3%, 0.2%, or 0.1% relative to the abundance of Lactobacillaceae present in the fecal sample from the healthy donor. In some aspects, a method disclosed herein comprising an administering step further comprises obtaining a fecal sample from the subject, determining the abundance of one or more bacteria of the genus Enterococcus, Lactobacillus, Bifidobacterium, Lactococcus, Streptococcus, Lacticaseibacillus, Blautia, o Eggerthella and / or one or more yeast of the genus Saccharomyces present in the fecal sample from the subject, obtaining a fecal sample from a healthy donor, determining the abundance of one or more bacteria of the genus Enterococcus, Lactobacillus, Bifidobacterium, Lactococcus, Streptococcus, Lacticaseibacillus, Blautia, ox Eggerthella and / or one or more yeast of the genus Saccharomyces present in the fecal sample from the healthy donor, and administering the composition to the subject if the abundance of one or more bacteria of the genus Enterococcus, Lactobacillus, Bifidobacterium, Lactococcus, Streptococcus, Lacticaseibacillus, Blautia, ox Eggerthella and / or one or more yeast of the genus Saccharomyces present in the fecal sample is less than 10% relative to the abundance of one or more bacteria of the genus Enterococcus, Lactobacillus, Bifidobacterium,Lactococcus, Streptococcus, Lacticaseibacillus, Blautia, or Eggerthella and / or one or more yeast of the genus Saccharomyces present in the fecal sample from the healthy donor. In some aspects, the composition is administered to the subject if the abundance of one or more bacteria of the genus Enterococcus, Lactobacillus, Bifidobacterium, Lactococcus, Streptococcus, Lacticaseibacillus, Blautia, o Eggerthella and / or one or more yeast of the genus Saccharomyces present in the fecal sample is less than about 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, 0.9%, 0.8%, 0.7%, 0.6%, 0.5%, 0.4%, 0.3%, 0.2%, or 0.1% relative to the abundance of one or more bacteria of the genus Enterococcus, Lactobacillus, Bifidobacterium, Lactococcus, Streptococcus, Lacticaseibacillus, Blautia, ox Eggerthella and / or one or more yeast of the genus Saccharomyces present in the fecal sample from the healthy donor.

[0210] In some aspects, a method disclosed herein comprising an administering step further comprises obtaining a fecal sample from the subject, determining the amount of a cellulose, a hemicellulose, a lignin, a lignan, or a combination thereof present in the fecal sample from the subject, obtaining a fecal sample from a healthy donor, determining the amount of the cellulose, the hemicellulose, the lignin, the lignan, or the combination thereof present in the fecal sample from the healthy donor, and administering the composition to the subject if the amount of the cellulose, the hemicellulose, the lignin, the lignan, or the combination thereof present in the fecal sample from the subject is more than the amount of the cellulose, the hemicellulose, the lignan, the lignin, or the combination thereof present in a fecal sample from the healthy donor.

[0211] In some aspects, a method disclosed herein comprising an administering step further comprises obtaining a fecal sample from the subject, determining the amount of a cellulose, a hemicellulose, a lignin, a lignan, or a combination thereof present in the fecal sample from the subject, obtaining a fecal sample from a healthy donor, determining the amount of the cellulose, the hemicellulose, the lignin, the lignan, or the combination thereof present in the fecal sample from the healthy donor, and administering the composition to the subject if the amount of the cellulose, the hemicellulose, the lignin, the lignan, or the combination thereof present in the fecal sample is more than 1000% relative to the amount of the cellulose, the hemicellulose, the lignin, the lignan, or the combination thereof present in the fecal sample from the healthy donor. In some aspects, the composition is administered to the subject if the amount of the cellulose, thehemicellulose, the lignin, the lignan, or the combination thereof present in the fecal sample is more than the amount of the cellulose, the hemicellulose, the lignin, the lignan, or the combination thereof present in the fecal sample from the healthy donor.Enumerated Embodiments

[0212] Embodiment 1. A composition comprising: a plurality of bacteria, and an extruded plant mass.

[0213] Embodiment 2. A composition comprising: a plurality of bacteria, and an extruded plant mass comprising a cellulose, a hemicellulose, a lignan, a lignin, or a combination thereof.

[0214] Embodiment 3. The composition of embodiment 1 or 2, further comprising N- trans-caffeoyltyramine (NCT) and / or N-trans-feruloyltyramine (NFT).

[0215] Embodiment 4. The composition of any one of embodiments 1-3, wherein the plurality of bacteria comprises only one species or strain of bacteria.

[0216] Embodiment 5. The composition of any one of embodiments 1-3, wherein the plurality of bacteria comprises two or more species or strains of bacteria.

[0217] Embodiment 6. The composition of any one of embodiments 1-5, wherein the plurality of bacteria comprises bacteria of the genus Lacticaseibacillus (formerly part of the genus Lactobacillus').

[0218] Embodiment 7. The composition of any one of embodiments 1-6, wherein the plurality of bacteria comprises bacteria selected from Lacticaseibacillus rhamnosus. Lacticaseibacillus casei, Lacticaseibacillus paracasei. or a combination thereof.

[0219] Embodiment 8. The composition of any one of embodiments 1-7, wherein the plurality of bacteria does not comprise Blautia producta, Eggerthella lenla. or both.

[0220] Embodiment 9. The composition of any one of embodiments 1-8, wherein the plurality of bacteria comprises spores.

[0221] Embodiment 10. The composition of any one of embodiments 1-9, wherein the plurality of bacteria comprises vegetative cells.

[0222] Embodiment 11. The composition of any one of embodiments 1-10, wherein the plurality of bacteria comprises a polynucleotide encoding an enzyme that catabolizes a cellulose, a hemicellulose, a lignan, or a lignin.

[0223] Embodiment 12. The composition of embodiment 11, wherein the plurality of bacteria comprises recombinant bacteria genetically engineered to comprise thepolynucleotide encoding the enzyme that catabolizes the cellulose, hemicellulose, lignan, or the lignin.

[0224] Embodiment 13. The composition of any one of embodiments 1-12, wherein the extruded plant mass comprises less than 2% wt / v N-trans-caffeoyltyramine (NCT) and / or N-trans-feruloyltyramine (NFT).

[0225] Embodiment 14. The composition of any one of embodiments 1-13, wherein the extruded plant mass is derived from a plant that produces N-trans-caffeoyltyramine (NCT) and / or N-trans-feruloyltyramine (NFT).

[0226] Embodiment 15. The composition of any one of embodiments 1-14, wherein the extruded plant mass is derived from a cannabis species.

[0227] Embodiment 16. The composition of any one of embodiments 1-15, wherein the extruded plant mass comprises a substance derived from seed hulls.

[0228] Embodiment 17. A comestible composition comprising the composition of any one of embodiments 1-16 and a nutritionally acceptable additive.

[0229] Embodiment 18. The comestible composition of embodiment 17, wherein the nutritionally acceptable additive comprises a prebiotic additive.

[0230] Embodiment 19. The comestible composition of embodiment 18, wherein the prebiotic additive comprises a prebiotic substance not present in the extruded plant mass.

[0231] Embodiment 20. The comestible composition of embodiment 18, wherein the prebiotic additive comprises a prebiotic substance present in the extruded plant mass.

[0232] Embodiment 21. The comestible composition of any one of embodiments 17-20, wherein the nutritionally acceptable additive comprises a flavoring agent, an odor masking agent, a coloring agent, a mouthfeel agent, or a combination thereof.

[0233] Embodiment 22. The comestible composition of any one of embodiments 17-21, wherein the comestible composition is in liquid form.

[0234] Embodiment 23. The comestible composition of any one of embodiments 17-21, wherein the comestible composition is in solid form.

[0235] Embodiment 24. The comestible composition of embodiment 23, wherein the comestible composition comprises one or more capsules or tablets.

[0236] Embodiment 25. The comestible composition of embodiment 23, wherein the comestible composition comprises a crisp (e.g., a protein crisp).

[0237] Embodiment 26. A pharmaceutical composition comprising the composition of any one of embodiments 1-16 and a pharmaceutically acceptable excipient.

[0238] Embodiment 27. The pharmaceutical composition of embodiment 26, comprising a prebiotic additive.

[0239] Embodiment 28. The pharmaceutical composition of embodiment 27, wherein the prebiotic additive comprises a prebiotic substance not present in the extruded plant mass.

[0240] Embodiment 29. The pharmaceutical composition of embodiment 27, wherein the prebiotic additive comprises a prebiotic substance present in the extruded plant mass.

[0241] Embodiment 30. The pharmaceutical composition of any one of embodiments 26- 29, wherein the pharmaceutically acceptable excipient comprises a flavoring agent, an odor masking agent, a coloring agent, a mouthfeel agent, or a combination thereof.

[0242] Embodiment 31. An oral dosage form comprising the pharmaceutical composition of any one of embodiments 26-30.

[0243] Embodiment 32. The oral dosage form of embodiment 31, wherein the pharmaceutical composition comprises a solution, slurry, suspension, or emulsion.

[0244] Embodiment 33. The oral dosage form of embodiment 31, wherein the pharmaceutical composition comprises a solid dosage form.

[0245] Embodiment 34. The oral dosage form of embodiment 33, wherein the solid dosage form comprises a powder, a capsule, or a tablet.

[0246] Embodiment 35. The oral dosage form of embodiment 34, comprising two or more capsules or tablets.

[0247] Embodiment 36. The oral dosage form of any one of embodiments 31-35, wherein the oral dosage form is formulated for delivery to the intestines.

[0248] Embodiment 37. The oral dosage form of embodiment 36, comprising an enteric polymer.

[0249] Embodiment 38. A method of preparing the composition of any one of embodiments 1-16, the comestible composition of any one of embodiments 17-25, the pharmaceutical composition of any one of embodiments 26-30, or the oral dosage form of any one of embodiments 31-37, comprising a step of pre-treating the plurality of bacteria.

[0250] Embodiment 39. The method of embodiment 38, wherein the step of pre-treating comprises germinating a plurality of spores.

[0251] Embodiment 40. The method of embodiment 38 or embodiment 39, wherein the step of pre-treating comprises growing a plurality of bacterial cells to logarithmic phase.

[0252] Embodiment 41. A method of treating or reducing the risk of a disease or disorder, of improving gut epithelial barrier integrity, of increasing gut transepithelial electrical resistance (TEER), or of increasing gut microbial diversity, comprising administering an effective amount of the composition of any one of embodiments 1-16, the comestible composition of any one of embodiments 17-25, the pharmaceutical composition of any one of embodiments 26-30, or the oral dosage form of any one of embodiments 31-37 to a subject in need thereof.

[0253] Embodiment 42. A method of treating or reducing the risk of a disease or disorder, or of improving gut epithelial barrier integrity, of increasing gut transepithelial electrical resistance (TEER), or of increasing gut microbial diversity, comprising administering to a subject in need thereof an effective amount of: a plurality of bacteria, and an extruded plant mass comprising a cellulose, a hemicellulose, a lignan, a lignin, or a combination thereof, wherein the extruded plant mass and the plurality of bacteria are not contained within the same dosage form.

[0254] Embodiment 43. A method of increasing the abundance of Lactobacilliaceae in the gut of a subject in need thereof, comprising administering to the subject an effective amount of: a plurality of bacteria, and an extruded plant mass comprising a cellulose, a hemicellulose, a lignan, a lignin, or a combination thereof.

[0255] Embodiment 44. The method of embodiment 42 or embodiment 43, wherein the plurality of bacteria further comprises and / or the extruded plant mass comprises N-trans- caffeoyltyramine (NCT) and / or N-trans-feruloyltyramine (NFT).

[0256] Embodiment 45. The method of embodiment 41 or embodiment 42, wherein the disease or disorder is selected from Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH).

[0257] Embodiment 46. The method of embodiment 41 or embodiment 42, wherein the disease or disorder is a gastrointestinal disease or disorder.

[0258] Embodiment 47. The method of embodiment 46, wherein the gastrointestinal disease or disorder is selected from irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), Crohn's disease (CD), ulcerative colitis (UC), and celiac disease. Other gastrointestinal disorders include, but are not limited to, necrotizing enterocolitis,indeterminate colitis, chronic colitis, HIV enteropathy, Helicobacter gastritis, NSAID- enteropathy / enteritis, pouchitis, discontinuous or patchy disease, ileal inflammation, extracolonic inflammation, granulomatous inflammation in response to ruptured crypts, aphthous ulcers, transmural inflammation, microscopic colitis, diverticulitis, diversion colitis, short bowel syndrome, GI mucositis, chemotherapy induced mucositis, radiation induced mucositis, and interstitial cystitis.

[0259] Embodiment 48. The method of any one of embodiments 41-47, wherein the abundance of Lactobacillaceae in the gut of the subject is increased following administration.

[0260] Embodiment 49. The method of any one of embodiments 41-48, wherein the abundance of bacteria of the family Enterobacteriaceae in the gut of the subject is not increased following administration.

[0261] Embodiment 50. The method of any one of embodiments 41-49, wherein the concentration of a short-chain fatty acid in the gut of the subject is increased following administration.

[0262] Embodiment 51. The method of embodiment 50, wherein the short-chain fatty acid comprises acetic acid, propanoic acid, or butyric acid.

[0263] Embodiment 52. The method of any one of embodiments 41-51, wherein the composition, the comestible composition, the pharmaceutical composition, or the oral dosage form is administered as two or more capsules daily.

[0264] Embodiment 53. The method of any one of embodiments 41-52, comprising: obtaining a fecal sample from the subject, determining the abundance of Lactobacillaceae present in the fecal sample from the subject, and administering the composition to the subject if the abundance of Lactobacillaceae present in the fecal sample from the subject is less than about 0.001%, 0.01%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 1.5%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 30%, 35%, 40%, 45%, or 50% relative to the total abundance of bacteria in the fecal sample.

[0265] Embodiment 54. The method of any one of embodiments 41-52, comprising: obtaining a fecal sample from the subject, determining the abundance of Lactobacillaceae present in the fecal sample from the subject, obtaining a fecal sample from a healthy donor, determining the abundance of Lactobacillaceae present in the fecal sample fromthe healthy donor, and administering the composition to the subject if the abundance of Lactobacillaceae present in the fecal sample is less than 10% relative to the abundance of Lactobacillaceae present in the fecal sample from the healthy donor.

[0266] Embodiment 55. The method of any one of embodiments 41-52, comprising: obtaining a fecal sample from the subject, determining the amount of a cellulose, a hemicellulose, a lignin, a lignan, or a combination thereof present in the fecal sample from the subject, obtaining a fecal sample from a healthy donor, determining the amount of the cellulose, the hemicellulose, the lignin, the lignan, or the combination thereof present in the fecal sample from the healthy donor, and administering the composition to the subject if the amount of the cellulose, the hemicellulose, the lignin, the lignan present, or the combination thereof in the fecal sample from the subject is more than the amount of the cellulose, the hemicellulose, the lignan, the lignin, or the combination thereof present in a fecal sample from the healthy donor.

[0267] Embodiment 56. The method of any one of embodiments 41-52, comprising: obtaining a fecal sample from the subject, determining the amount of a cellulose, a hemicellulose, a lignin, a lignan, or a combination thereof present in the fecal sample from the subject, obtaining a fecal sample from a healthy donor, determining the amount of the cellulose, the hemicellulose, the lignin, the lignan, or the combination thereof present in the fecal sample from the healthy donor, and administering the composition to the subject if the amount of the cellulose, the hemicellulose, the lignin, the lignan, or the combination thereof present in the fecal sample is more than the amount of the cellulose, the hemicellulose, the lignin, the lignan, or the combination thereof present in the fecal sample from the healthy donor.ExamplesExample 1. An extruded hemp hull fiber composition enhances the growth of Lacticaseibacillus paracasei

[0268] A hemp hull fiber composition designed to support gut health was formulated for use in food and beverages. The hemp hull fiber composition was an extruded hemp hull composition comprising, among other substances, two compounds, N-trans-caffeoyl tyramine (NCT) and N-trans-feruloyl tyramine (NFT). Compositions of hemp hull fiber, e.g., a hemp hull fiber powder, and methods of their manufacture are described in one ormore of W02019140052A1, WO2021096813A1, W02019140046A1, WO2023141427A1, WO2022081567A1, WO2021081222A1, WO2021119020A1, each of which is incorporated in its entirety herein.

[0269] To determine the effect of the presence or absence of the hemp hull fiber composition on the growth of Lacticaseibacillus paracasei (L. paracasei , growth experiments were performed, the results of which are presented in Fig. 2. 7 mL of HiVeg media was aliquoted into each of two separate 15 mL tubes. Several colonies of Lacticaseibacillus paracasei ATCC 11578 were inoculated into one tube, while the other tube remained as a sterility control. Both tubes were incubated about 24 hours at about 37 °C. No growth was observed in the sterility control.

[0270] Eighteen 15-mL tubes were collected and labeled for triplicate studies evaluating the growth of L. paracasei. The test conditions were: (1) L. paracasei + 20 mg / mL of the hemp hull fiber composition, (2) L. paracasei + 10 mg / mL of the hemp hull fiber composition, (3) L. paracasei + 5 mg / mL of the hemp hull fiber composition, (4) L. paracasei only (L. paracasei in HiVeg media only, without the hemp hull fiber composition), (5) HiVeg media only (no L. paracasei, without the hull hemp fiber composition), and (6) HiVeg media + 20 mg / mL of the hull hemp fiber composition (no L. paracasei).

[0271] In triplicate, tubes were filled with (1) 200 mg, (2) 100 mg, or (3) 50 mg of the hemp hull fiber composition, then filled to a final volume of 10 mL with BSD HiVeg media. The remaining six tubes (conditions 5 and 6) were filled with 10 mL BSD HiVeg media in the absence of the hemp hull fiber composition. All tubes were autoclaved and cooled.

[0272] The tubes were placed in a growth chamber under reducing conditions for about 1 hour. 100 pL of the L. paracasei 24-hour culture was added to each tube except for the no-bacteria tubes for conditions (5) HiVeg media only (no L. paracasei, without the hemp hull fiber composition) and (6) HiVeg media + 20 mg / mL of the hemp hull fiber composition (no L. paracasei . All tubes were incubated for about 24 hours at about 37 °C. A 1 mL sample from each tube was tested for optical absorbance at 600 nm (OD600). An increase in OD600 over time corresponds to growth of the bacteria in a tube.

[0273] The results are summarized in Fig. 2. As shown, L. paracasei grew more in the presence of 20 mg / mL of the hemp hull fiber composition than in the absence of the hemphull fiber composition (p=0.0038). Accordingly, the hemp hull fiber composition is useful to enhance the growth of L. paracasei.Example 2. An extruded hemp hull fiber composition enhances the growth of Lacticaseibacillus rhamnosus and Lacticaseibacillus casei

[0274] To determine the effect of the presence or absence of the hemp fiber composition on the growth of additional bacteria, further growth experiments were performed. The protocol of Example 1 was followed, but only with 20 mg / mL of the hemp hull fiber composition in the tests containing the hemp hull fiber composition, with each of the following bacterial strains tested: Eggerthella lenta ATCC 43055, Lactobacillus rhamnosus ATCC 7469 (now known as Lacticaseibacillus rhamnosus), Lactobacillus casei ATCC 393 (now known as Lacticaseibacillus casei), Blautia producta ATCC 27340 (formerly Ruminococcus productus), and Eggerthella lenta ATCC 25559.

[0275] The results are summarized in Fig. 3. The presence of 20 mg / mL of the hemp hull fiber composition did not enhance growth of either E. lenta strain. B. producta growth was also not enhanced in the presence of 20 mg / mL of the hemp hull fiber composition. Both Lacticaseibacillus bacteria tested showed significantly increased growth in the presence of 20 mg / mL of the hemp hull fiber composition at 24 hours (L. rhamnosus, p=0.00005; L. casei, p=0.005) and at 48 hours (L. rhamnosus, p=0.001; L. casei, p=0.003). Taken together with the results of Example 1, all three of the Lactobacillaceae bacteria tested grew more in the presence of 20 mg / mL of the hemp hull fiber composition.Example 3. Determining enhanced growth of bacteria in the presence of a hemp hull fiber composition (Prophetic)

[0276] Given the disclosure and positive results of Examples 1 and 2, other members of the family Lactobacillaceae are expected to grow more in the presence of a hemp hull fiber composition. A skilled artisan can determine other bacterial species with enhanced growth in the presence of a hemp hull fiber composition, including at 20 mg / mL of a hemp hull fiber composition.

[0277] A growth experiment is carried out according to the protocol of Example 1, testing a bacterial species or strain not tested in Example 1 or Example 2. The hemp hull fiber composition is found to enhance the growth of the bacterial species or strain.Example 4. Enhancing probiotic growth with a hemp hull fiber composition.

[0278] Previous ex vivo studies have demonstrated that a hemp hull fiber composition enhances microbiome diversity and productivity (Martinez et al. Hemp hull fiber and two constituent compounds, N-trans-caffeoyltyramine and N-trans-feruloyltyramine, shape the human gut microbiome in vitro. Food Chem X. 2024 Jul 2;23: 101611. doi: 10.1016 / j.fochx.2024.101611. PMID: 39113742; PMCID: PMC11304861, incorporated by reference herein). To determine potential for a hemp hull fiber composition to support the growth of commercially available probiotics, nine representative probiotic strains were cultivated in the presence of a hemp hull fiber composition. mBHI (Martinez et al. Hemp hull fiber and two constituent compounds, N-trans-caffeoyltyramine and N-trans- feruloyltyramine, shape the human gut microbiome in vitro. Food Chem X. 2024 Jul 2;23: 101611. doi: 10.1016 / j.fochx.2024.101611. PMID: 39113742; PMCID:PMC 11304861) was used as culture media or was supplemented with a hemp hull fiber composition (2% w / v). A 100 pl culture in a 96-well plate was inoculated 1% of seed culture under strict anaerobic condition. The 96-well plate was sealed with parafilm and incubated at 37°C for 24h. Optical density (OD) at 600 nm was measured every 5 min over 24 hour of growth (288 time points), and before each measurement, the plate was shake at 200 rpm for 20s.

[0279] The results indicated that, compared to culture media alone, hemp hull fiber composition supplementation promoted a more rapid growth phenotype and exhibited a characteristic pause-restart pattern across strains. Without wishing to be bound by any one theory, the initial rapid growth phase suggests that hemp hull fiber composition may facilitate early-stage proliferation, although the underlying mechanism(s) is not clear. The observed pause-restart pattern implies that the tested strains could utilize hemp hull fiber composition as an alternative carbon source upon depletion of the primary sugar component (0.2% glucose in mBHI), which typically occurs around 5 hours. Most of the tested strains showed a signature pause of growth around 5 h after inoculation. The results are summarized in Figures 1 A-l J.Example 5. Probiotic supplementation enhances the release of bioactive compounds from a hemp hull fiber composition.

[0280] Metabolite profiling using LC-MS / MS was performed to measure the relative abundance of N-trans-caffeoyltyramine (NCT) and N-trans-feruloyltyramine (NFT) andmetabolites in cultures of the probiotics of Example 4 supplemented with hemp hull fiber composition, compared to hemp hull fiber composition alone.Sample Extraction

[0281] In preparation for mass spectrometry analyses, 1 mL of each sample was aliquoted to different wells on a 96-well deep well plate. The plate was then vacuum-dried using a Genevac HT-12 and resuspended with 500 pL of 95% acetonitrile in water containing isotope labeled internal standards, vortexed, and centrifuged at 15,000 x g for 10 minutes. The resulting supernatants were transferred to autosampler vials for LC-MS analysis.Liquid Chromatography Mass Spectometry (LC-MS) Analysis

[0282] A Thermo Vanquish High Performance Liquid Chromatograph coupled to a Thermo ID-X tandem mass spectrometer was used for analyses (ThermoScientific, Waltham, MA). Chromatographic separation was achieved using a Hypersil Cl 8 column (ThermoScientific, Waltham, MA). The mobile phases used were Optima grade water with 0.1% formic acid (A) and Optima grade acetonitrile with 0.1% formic acid (B). To chromatographically separate these complex matrices, the gradient started at 0% B and increased to 100% B over 10 minutes.

[0283] Mass spectral data were collected across the runs using data dependent analysis (DDA) with 25% normalized collision energy (NCE) collision induced dissociation (CID). Mass spectra were collected using both positive and negative electrospray ionization (ESI). A process blank and pooled quality control sample were injected after every tenth sample for background subtraction and data quality assurance. Otherwise, all sample injections were randomized to neutralize any biases arising from sample storage or evaporation.Data Processing and Compound Annotation

[0284] All data were processed using MS-DIAL (prime.psc.riken.jp / compms / msdial / main.html) for peak detection, deconvolution, library matching, and alignment. The aligned output was filtered to remove any features that were less than 10-fold higher in the samples than in the blanks, not present in all replicates of any one single sample type, or for which no fragmentation information was collected.

[0285] High-confidence annotations were identified using a curated mass spectral library including publicly available databases such as NIST20, MassBank of North America (MoNA) (mona.fiehnlab.ucdavis.edu / ); MassBank Europe (massbank.eu / MassBank / ) and Wiley, as well as an in-house library of more than 15,000 pure compounds. All features measured were annotated by MSI, MS / MS, and retention time comparison, and the resulting annotations were assigned confidence levels by manual interpretation in accordance with MSI guidelines (Schymanski et al., Environmental Science & Technology 2014 48 (4), 2097-2098 DOI: 10.1021 / es5002105). The aligned data was then normalized by sample sum (mTIC normalization) to account for variations in sample richness and to focus on true biological differences.Results

[0286] The LC-MS / MS analysis revealed a higher relative abundance of NCT and NFT in probiotic-supplemented cultures compared to hemp hull fiber composition alone (Table 1). Without wishing to be bound by any one theory, these initial findings suggest that probiotic strains may facilitate the release of bioactive small molecules by degrading fiber components within hemp hull fiber composition, thereby enhancing the bioavailability of these compounds.Table 1. Metabolomic profiling of compounds by LC-MS / MS analysis comparing probiotics supplemented with hemp hull fiber composition versus hemp hull fiber composition alone. Fold change indicates the relative increase in compound abundance in probiotic-supplemented cultures, which was calculated across all individual strains of Example 4 that were supplemented with hemp hull fiber composition versus hemp hull fiber composition alone.Example 6. An upcycled dietary fiber rich in bioactives from hemp hulls supports digestive comfort in healthy adults

[0287] Different sources of fiber exert benefits and challenges based on their physicochemical properties. Solubility has long been used as the classification for fiber benefit, with soluble fibers gaining more attention over insoluble fibers. Attributes of fiber such as viscosity and fermentability, however, are more indicative of the health benefit. Solubility is an analytical definition that does not necessarily predict the physiological benefit of the dietary fiber (Timm, M.; Offringa, L.C.; Van Klinken, B.J.- W.; Slavin, J. Beyond Insoluble Dietary Fiber: Bioactive Compounds in Plant Foods. Nutrients 2023, 75, doi: 10.3390 / nul5194138; Lattimer, J.M.; Haub, M.D. Effects of Dietary Fiber and Its Components on Metabolic Health. Nutrients 2010, 2, 1266-1289, doi: 10.3390 / nu2121266).

[0288] Fermentable fibers such as inulin, oligofructose, fructooligosacchrides, and galactooligosaccharides, support gut health through a prebiotic mechanism and generation of key metabolites such as short-chain fatty acids (Carlson, J.L.; Erickson, J.M.; Lloyd, B.B.; Slavin, J.L. Health Effects and Sources of Prebiotic Dietary Fiber. Curr Dev Nutr 2018, 2, nzy005, doi: 10.1093 / cdn / nzy005). While these fibers have gained significant attention for their prebiotic benefit for gut health, they are accompanied by digestive side effects that can impact quality of life (Mysonhimer, A.R.; Holscher, H.D. Gastrointestinal Effects and Tolerance of Nondigestible Carbohydrate Consumption. Adv Nutr 2022, 73, 2237-2276, doi: 10.1093 / advances / nmac094; Grabitske, H.A.; Slavin, J.L. Low- Digestible Carbohydrates in Practice. J Am Diet Assoc 2008, 108, 1677-1681, doi: 10.1016 / j.jada.2008.07.010). Digestive tolerance is indicated by the perceived gastrointestinal symptoms such as abdominal pain / cramping, bloating, burping, flatulence, nausea, rumbling noises (borborygmi), and acid reflux (heartbum) (Mysonhimer et al., 2022). Many of these perceived symptoms are tied directly to gas production in the gut, which is a byproduct of fiber fermentation. While these symptoms typically do not pose long-term health concerns, they result in discomfort, reduced quality of life, and are socially unacceptable, and consumers discontinue consuming the fiber.

[0289] Many fermentable fibers have low tolerance thresholds, which can negatively impact user experience. In a comprehensive review of gastrointestinal tolerance of dietary fibers, the lowest tolerance thresholds, based on human clinical studies, were 3.5 g / day alginate, 5 g / day inulin and 7.5 g / day fructooligosaccharide (Mysonhimer et al., 2022). This aligns with the FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) approach that suggests limitation of certain fermentable dietary fibers to manage digestive symptoms (Gibson, P.R.; Shepherd, S.J. Evidence- Based Dietary Management of Functional Gastrointestinal Symptoms: The FODMAP Approach. J Gastroenterol Hepatol 2010, 25, 252-258, doi: 10.1111 / j .1440- 1746.2009.06149.x ). Hemp hull fiber is low in FODMAPs, as it contains 50% cellulose, with the remaining fibers made up of hemicellulose and lignin (van Klinken, B.J.-W.; Stewart, M.L.; Kalgaonkar, S.; Chae, L. Health-Promoting Opportunities of Hemp Hull: The Potential of Bioactive Compounds. J Diet Suppl 2024, 1-15, doi: 10.1080 / 19390211.2024.2308264; Atzler, J. J.; Sahin, A.W.; Gallagher, E.; Zannini, E.; Arendt, E.K. Characteristics and Properties of Fibres Suitable for a Low FODMAPDiet- an Overview. Trends in Food Science & Technology 2021, 772, 823-836, doi: 10.1016 / j.tifs.2021.04.023). While the recommended intakes for dietary fiber in the US (adequate intake) are 28 g / d for women and 35 g / d for men, these tolerance levels demonstrate that a mixture of dietary fibers is necessary to meet target intake levels (Dietary Reference Intakes: The Essential Guide to Nutrient Requirements |The National Academies Press Available online: nap.nationalacademies.org / download / 11537). This is best addressed by including multiple sources of fiber that span the spectrum of fermentability.

[0290] The lesser-known benefits of naturally-occurring fibers need to be highlighted to increase consumer awareness and incorporation into the diet as a fiber source. Many of these fibers have higher digestive tolerance due to the metered bacterial fermentation rate in the gut (Mysonhimer et al., 2022). With a slower bacterial fermentation rate in the colon, the rate of gas production is also slower. This enables the digestive system to equilibrate the gas more readily, thus reducing the perceived symptoms. Insoluble fibers can provide benefits to gut health via prolonged fermentation in the gut, allowing beneficial metabolites such as short-chain fatty acids to be produced in the distal colon and thereby providing the prebiotic benefit, without the GI discomfort associated with rapidly fermenting soluble fiber (Wong, J.M.W.; de Souza, R.; Kendall, C.W.C.; Emam, A.; Jenkins, D.J.A. Colonic Health: Fermentation and Short Chain Fatty Acids. J Clin Gastroenterol 2006, 40, 235-243, doi: 10.1097 / 00004836-200603000-00015).

[0291] In the literature, much of the evaluation of dietary fibers and digestive tolerance is limited to single fiber interventions. The present study, however, compared perceived quality of life, digestive symptoms, and anxiety while consuming one of two sources of dietary fiber, inulin or hemp hull fiber, or a placebo, maltodextrin, over the course of 6 weeks.

[0292] This completely virtual, randomized, parallel arm study is the first study to evaluate the perceived digestive comfort when consuming Bio Gut Fiber - a proprietary hemp hull fiber and a source of insoluble dietary fiber with bioactive components (van Klinken et al., 2024).Materials and MethodsStudy Subjects

[0293] This was a completely virtual, randomized, double-blinded, placebo-controlled study in adults aged 21 years or older living in the United States, administered by Radicle Science, Del Mar, California, USA. The protocol was reviewed and approved by the Institutional Review Board affiliated with Radicle Science. The study is registered in ClinicalTrials.gov under protocol number NCT06009614.

[0294] Since the study was conducted completely remotely, the study subjects were recruited online using several means of engagement: internet-based networks, retailers, and advocacy group distribution lists and email.

[0295] Subjects were recruited based on their intention to seek relief from GI related discomfort. The inclusion-exclusion criteria listed in Table 2 were used for subject enrollment. Eligible subjects provided informed consent and were enrolled in the study.Table 2. Subject Eligibility Criteria

[0296] Subjects were randomized to a study arm using a block randomization scheme that was stratified by sex assigned at birth and baseline Digestion-associated Quality of Life Questionnaire scores (Table 3).Table 3. Validated health measures used in the studyStudy Protocol

[0297] The study had an intervention duration of 6 weeks (42 days). Subject were randomly assigned to receive one of three study products:• Test product: Brightseed® Bio Gut Fiber (BGF), a hemp hull fiber, (Brightseed, San Francisco, CA, USA), a proprietary hemp hull fiber with bioactives at a dose providing 2.8 g fiber / day.• Comparator product: Inulin (Beneo, Mannheim, Germany), dose providing 2.8 g fiber / day. Maltodextrin was added to 4 g.• Placebo: Maltodextrin (Grain Processing Corporation, Washington, IN, USA), 4 g dose to approximately match total test and comparator product administered

[0298] All products were matched for weight and color. Fiber dose was chosen to provide 10% Daily Value or a “Good Source of Fiber” per United States fiber intake recommendations (Dietary Reference Intakes: The Essential Guide to Nutrient Requirements |The National Academies Press Available online: nap.nationalacademies.org / download / 11537). Subjects were shipped enough study products for the 6-week intervention. The subjects were asked to confirm receipt of the products and confirm the identity of the product code, to ensure they received the correct study products. Subjects were instructed to consume one sachet of product each day for the 6-week duration of the study. Subjects did not receive any financial compensation for participating in the study but rather were provided with a personalized health report based on the responses they provided.

[0299] Each week, subjects completed validated surveys through a secure, online platform. Automated reminders were sent to the subjects via text message and / or email. Table 3 lists the validated surveys used in this study. The primary outcome was to detect significant differences in the perceived Digestion-associated Quality of Life Questionnaire (DQLQ). Secondary outcomes assessed perceived belly pain, gas and bloating, and reported side effects using Patient-Reported Outcomes Measurement Information System (PROMIS™) instruments.

[0300] A sample size calculation was conducted to ensure sufficient power to detect a significant difference in the effect on the primary outcome between each active product group and the control group. A Monte Carlo power analysis was conducted to determine the sample size required to detect a small effect size equal to a generalized Cohen’s D = 0.2 (which translates to a Cohen’s D of 0.302) at a two-sided p-value of 0.05 between the slopes of the control group and the active product groups, and the planned pairwise comparisons the active product groups; Bonferroni correction was applied. For a power of 80% and accounting for up to 40% attrition, the required sample size is 250 participants per study arm.ResultsSubject characteristics and retention

[0301] A total of 948 subjects were randomized to a treatment arm and shipped the study products. In all treatment arms, the majority was female, white, and either overweight or obese, with a mean age of approximately 43 years (Table 4).Table 4. Subject Demographics- RandomizedBGF = Bio Gut Fiber; mITT= Modified Intent to Treat; PP = Per Protocol;BMI= Body mass index

[0302] The modified intent to treat (mITT) population was defined as the subjects (n=579) that completed at least one post baseline questionnaire at any time during the six weeks intervention period. Dropout rates were similar among the treatment arms. Twelve percent of the originally randomized subjects completed all six post-baseline questionnaires (n=l 14), which is the basis for the per-protocol analysis. As a fully remote / virtual study, this attrition rate was anticipated. The study was powered sufficiently such that this loss of subjects to follow-up did not impact statistical significance. Discontinuations tended to be from young males which slightly increased the proportion and ages of females in the mITT and PP populations.Table 5. Subject demographics- mITT and PP PopulationsBGF = Bio Gut Fiber; mITT= Modified Intent to Treat; PP = Per Protocol; BMI= Body mass indexStatistical Analysis

[0303] In an effort to utilize all available data due to the high dropout rate, the modified intent-to-treat (mITT) population was used as the primary analysis population for assessing outcomes over time. A mixed model repeated measures analysis of covariance (MMRM) method was used to analyze survey total score changes over 6 weeks.

[0304] The MMRM model for DQLQ Score, Belly Pain Score, and Gas and Bloating Score, respectively, included effects for study arm, week, interaction between arm and week, and included baseline scores for the specific outcome as a covariate. Subjects were random blocking factors and a variance component option was used for the covariance structure of the R matrix. This same model was run for mITT and PP populations, for each outcome. All data are presented as least squares mean (LSM) to best address the level of missingness in the data set. All treatment means are reported with LSM and standard error by week.

[0305] For both populations, mITT and PP, the models converged indicating statistically significant difference among Study Arms, among Weeks, but not for the interactionbetween Arms and Weeks. In both analyses, the baseline total score was a significant covariate for all outcomes and was included in the analysis models.Survey Results

[0306] All study arms, including placebo, resulted in a notably decreased survey scores from baseline to week 1, irrespective of the outcome assessed. The scores reported during week 2 through week 6 never returned to the baseline level for any of the treatment arms (Figs. 4A, 4B, 5A, 5B, 6A, 6B, 7A, and 7B), indicating an improvement in perceived digestive symptoms.

[0307] There were no study arm differences in LSM baseline for total DQLQ score, belly pain, or gas and bloating scores. The significant differences between treatment groups by week varied depending on the outcome assessed. These are described outcome by outcome in the next subsections.Digestion Associated Quality of Life Questionnaire (DQLQ) Scores

[0308] The DQLQ mITT LSM scores dropped from 4.14-4.22 to 1.93-2.17 between baseline and week 1 (Fig. 4A and 4B) for both treatments and placebo. The DQLQ mITT scores were significantly different only at week 3, between BGF and inulin. The DQLQ PP scores exhibited a similar trend to the mITT scores, dropping from 3.91- 4.07 to 1.41- 2.32 between baseline and week 1. Bio Gut Fiber consumption yielded significantly lower DQLQ PP scores compared to inulin at week 1, week 5, and week 6. Bio Gut Fiber yielded significantly lower DQLQ PP scores compared to placebo at week 6.PROMIS Belly Pain Scores

[0309] Over time, participants experienced, on average, a greater than 8-point decrease from baseline in total Belly Pain scores across all groups in both mITT and PP (Fig. 5A and 5B). This represents nearly a 50% reduction in total belly pain scores for all treatment arms. Similar to the trend seen with the DQLQ scores. Belly Pain mITT LSM scores dropped from 14.88-15.13 to 9.76-10.19 from baseline to week 1. Bio Gut Fiber consumption yielded significantly lower belly pain scores compared to inulin at week 2, week 4, week 5, and week 6. Placebo consumption yielded significantly lower belly pain scores compared to inulin at week 6. The Belly Pain PP LSM scores also dropped from 14.31-14.99 at baseline to 8.84-10.86 at week 1. The PP analysis exhibited a trend similarto the mITT analysis. Bio Gut Fiber consumption yielded significantly lower belly pain scores compared to inulin at weeks 4, 5, and 6. At week 1, placebo consumption resulted in significantly lower belly pain scores than inulin, while BGF consumption was trending toward being significantly lower (p=0.0662).PROMIS Gas & Bloating Scores

[0310] As seen with the DQLQ score and belly pain score, the gas and bloating score for all study arms exhibited the greatest decrease from baseline (32.26-32.80) to week 1 (21.87-24.13) in the mITT analysis as well as the PP analysis (30.87-33.09 baseline to 20.00-25.81 week 1, Fig. 6A and 6B). Over time, participants experienced on average > 11 -point decrease from baseline in total Gas and Bloating scores across all groups. This represents nearly a 35% reduction in total Gas and Bloating scores. In the mITT analysis, placebo intake resulted in significantly lower gas & bloating scores compared with inulin at weeks, 1, 2, 4, 5 and 6. Bio Gut Fiber consumption also yielded significantly lower gas and bloating scores compared to inulin at weeks 4, 5, and 6. The PP scores exhibited a similar trend, but the pairwise differences were only significant at week 4 (placebo vs inulin) and week 6 (BGF vs inulin). At both time points, inulin resulted in significantly greater scores than the other treatments.PROMIS Anxiety Scores

[0311] The PROMIS anxiety scores followed the same downward trend as the digestive comfort scores previously described. The baseline LSM scores were highest for all treatments in mITT (10.04-10.22) and PP (9.19-9.63) analysis, dropping at week 1 to 7.75-8.38 for mITT and 6.94-7.22 for PP (Fig. 7A and 7B). Anxiety scores were significantly lower for placebo compared to inulin at weeks 1, 2, and 5 for the mITT analysis. Bio Gut Fiber consumption resulted in significantly lower anxiety scores at week 5 compared to inulin, also. The only significantly different time point in the PP analysis was at week 6, with BGF consumption resulting in lower anxiety scores compared to placebo.Side Effects

[0312] The incidence of reported side effects were similar for BGF (22.7%), Inulin (28.7%) and Placebo (29.0%) (see Klinken B. J. W ., D' Adamo C. R., Pauli E. K.,Kalgaonkar S. An upcycled dietary fiber rich in bioactives from hemp hulls supports digestive comfort in healthy adults: Randomized, placebo-controlled trial. Bioactive Compounds in Health and Disease 2024; 7(12): 594-609). Most of the side effects were classified as gastrointestinal concerns (stomach cramps, diarrhea, and gas / bloating) followed by nervous system symptoms (headache and insomnia). Other side effects included changes in feeling of energy, caffeine sensitivity, urinary concerns, and respiratory concerns.Discussion

[0313] Subject compliance can be challenging in a decentralized, remote study. Based on the reported daily intake and weekly frequency, subject compliance for those that continued to stay enrolled was acceptable and met expectations for data analysis. In a recent remote study on sleep, 27% of subjects enrolled in the study dropped out prior to the first data collection (Saleska, J.L.; Bryant, C.; Kolobaric, A.; D’ Adamo, C.R.; Colwell, C.S.; Loewy, D.; Chen, J.; Pauli, E.K. The Safety and Comparative Effectiveness of Non-Psychoactive Cannabinoid Formulations for the Improvement of Sleep: A Double-Blinded, Randomized Controlled Trial. J Am Nutr Assoc 2024, 43, 1- 11, doi: 10.1080 / 27697061.2023.2203221). This study experienced a slightly higher dropout rate, with 39% of enrolled subjects being lost to follow up and completing zero study visits. This may be a result of the lack of compensation for participating in the study or subject dislike of the study products.

[0314] A mITT analysis approach was taken to utilize the data collected from subjects who completed at least one study visit. This method is fairly robust in a study with multiple missing data points. However, approximately 48% of the expected outcomes were missing over the 6-week period. Therefore, to assess if estimated study arm differences are robust against this level of missingness, data were also analyzed using mixed model repeated measure (MMRM) method on the subset of PP population where there are no missing outcomes at any week.

[0315] Due to the attrition of participants over time, the final mITT dataset contained approximately 55% of the total expected data if all participants had completed all 6 weeks of questionnaires. However, this is far better than 12% of total expected data when a perprotocol definition is utilized, which is why a MMRM methodology for analyzing the data is preferred as it preserves all collected data. Even with the robust handling ofmissing data, problems in model convergence and adequate estimation of least squares means and intervention effects can arise. Therefore, the interpretation of outcomes were compared using both the MMRM approach on the mITT population to the PP population which represents the purest subset of participants who completed all study requirements.

[0316] Bio Gut Fiber intake yielded lower digestive symptom scores than inulin. This finding aligns with inulin having a relatively low digestive tolerance of 5 grams per day to avoid flatulence (Mysonhimer et al., 2022). In previous studies, both flatulence and bloating were reported at moderate intake of 2.0 to 7.5 grams per day. The findings in the present study, where the gas and bloating scores after consuming inulin were significantly higher than placebo and BGF at multiple time points, are supported by the current body of knowledge. This is likely due to inulin’s rapid fermentation rate which yields gas along with beneficial metabolites such as short-chain fatty acids (Stewart, M.L.; Timm, D.A.; Slavin, J.L. Fructooligosaccharides Exhibit More Rapid Fermentation than Long-Chain Inulin in an in Vitro Fermentation System. Nutr Res 2008, 28, 329-334, doi: 10.1016 / j.nutres.2008.02.014; Grabitske, H.A.; Slavin, J.L. Gastrointestinal Effects of Low-Digestible Carbohydrates. Crit Rev Food Sci Nutr 2009, 49, 327-360, doi: 10.1080 / 10408390802067126). While the short-chain fatty acids support digestive health, excessive and rapid gas production by the gut microbiota can yield discomfort. This may ultimately lead to an individual avoiding certain fibers to prevent discomfort (Mutuyemungu, E.; Singh, M.; Liu, S.; Rose, D.J. Intestinal Gas Production by the Gut Microbiota: A Review. Journal of Functional Foods 2023, 100, 105367, doi: 10.1016 / j.jff.2022.105367).

[0317] Placebo intake resulted in lower digestive symptom scores compared to baseline for all outcomes. It is unlikely that there was a physiological change in gut function when the placebo, a fully digestible, corn-based maltodextrin, was consumed. This indicates that participating in the study in and of itself resulted in a change in perceived digestive symptoms (a placebo effect). However, there were notably higher Gas and Bloating scores when inulin was consumed compared to placebo in the ITT analysis during 5 of the 6 weeks. Week 3 was trending towards a significant difference (p = 0.0576) between placebo and inulin. The increased Gas and Bloating scores after consuming inulin correspond with increased Anxiety scores for inulin, compared to placebo, at weeks 1, 2,and 5 in the mITT analysis. Thus, the digestive symptoms may have influenced the perceived anxiety for the subjects.

[0318] The placebo effect noted in this study has been documented in other publications. Particularly when perceived gastrointestinal symptoms are measured, there can be a substantial placebo effect. Research on functional dyspepsia has reported placebo response rates ranging from 6% to 72% (Musial, F.; Klosterhalfen, S.; Enck, P. Placebo Responses in Patients with Gastrointestinal Disorders. World J Gastroenterol 2007, 13, 3425-3429, doi: 10.3748 / wjg.vl3.i25.3425). When irritable bowel syndrome was studied, placebo response rates ranged from 3% to 84% across trials (Lu, C.-L.; Chang, F.-Y. Placebo Effect in Patients with Irritable Bowel Syndrome. J Gastroenterol Hepatol 2011, 26 Suppl 3, 116-118, doi: 10.1111 / j.1440-1746.2011.06651.x). While both of these situations involved the study of patients with a declared diseases and the present study examined healthy individuals that were experiencing self-reported gastrointestinal discomfort, it demonstrates that placebo effects in digestive symptom studies have been previously reported.

[0319] Dietary fiber has been identified as a shortfall nutrient in the American diet for decades (Dietary Guidelines Advisory Committee Scientific Report of the 2020 Dietary Guidelines Advisory Committee: Advisory Report to the Secretary of Agriculture and the Secretary of Health and Human Services; U.S. Department of Agriculture, Agricultural Research Service, 2020; p. 835). On average, Americans consume only half of the recommended intake of dietary fiber. Fiber supplements and fiber fortified foods are approaches to close this gap. However, not all fibers provide the same physiological benefits, and likewise, not all fibers have the same digestive tolerance. This study demonstrates that hemp hull fiber, when consumed at a “Good Source” of fiber level (2.8 grams per day), results in lower digestive distress than inulin, when consumed at the same level. Also, surprisingly, consumers perceive a difference in GI distress with a dose as low as 2.8 gr / day. Because this study included such a large group of participants, the study was uniquely able to tease out such a small effect.

[0320] One differentiator between the two types of fiber administered is the inclusion of bioactive compounds. Hemp hull fiber includes bioactive compounds that can support health and well-being, beyond the digestive tract. A recent review describes accompanying total phenolic compounds, total flavonoid content and antioxidant activityof sources of insoluble fiber (Timm et al., 2023). In addition to providing dietary fiber with improved digestive tolerance, insoluble fiber sources such as BGF, can also increase bioactive compound intake to support health. Highly fermentable fibers, such as inulin, have been associated with digestive wellness benefits (e.g. prebiotic effect) and also digestive discomfort (Eswaran, S.; Muir, J.; Chey, W.D. Fiber and Functional Gastrointestinal Disorders. Am J Gastroenterol 2013, 108, 718-727, doi: 10.1038 / ajg.2013.63). However, inulin is among the sources of soluble fiber that increase abdominal pain, bloating, and flatulence, which can result in undue discomfort (Barrett, J.S. Extending Our Knowledge of Fermentable, Short-Chain Carbohydrates for Managing Gastrointestinal Symptoms. Nutr Clin Pract 2013, 28, 300-306, doi: 10.1177 / 0884533613485790). The multi-faceted benefit of slowly fermented fibers reinforces their value in a health-promoting diet.Conclusions

[0321] This study demonstrated that BGF, a source of naturally-occurring fiber and bioactives, is well tolerated by healthy adults when consumed in a practical dose. Digestive comfort after consuming BGF improved compared to baseline and was significantly better than inulin at multiple points during the intervention. This study provides that inulin intake can result in noticeable digestive symptoms, which may deter individuals from consuming this type of fiber. Including BGF as a part of a balanced diet can enable an individual to meet dietary fiber intake goals while experiencing minimal digestive side-effects.

[0322] Taken together, a composition of the present disclosure, comprising insoluble fiber and, for example, fiber having a decreased fermentation rate, results in a higher tolerance profile than, e.g., inulin. Therefore, in some aspects, the present disclosure provides a composition of plant mass, for example, comprising hemp hull fiber, that is better tolerated than inulin and / or reduces gastrointestinal discomfort relative to administration of an equivalent mass of inulin. Further, addition of a probiotic, such as a bacteria or yeast, to a composition comprising hemp hull fiber as described herein can provide additional improved digestive benefits from, for example, release of metabolites from the bacteria and / or yeast.Example 7. Administration of a disclosed composition

[0323] A composition as disclosed herein is administered to enhance the growth of bacteria and / or yeast in a subject, wherein the bacteria and / or yeast is determined to have increased growth in the presence of a hemp hull fiber composition in an in vitro experiment according to any one of Examples 1-4.

[0324] For example, a dietary supplement is provided as two capsules to be administered orally, once per day. The supplement is provided in a screw-cap bottle containing 100 capsules. Each serving of two capsules contains, distributed among the two capsules, 1 g of a hemp hull fiber composition (or another composition disclosed herein) and 20 mg of prebiotic additives NCT and NFT.

[0325] The dietary supplement is suitable for co-administration with one or more probiotics, which can be administered before, concurrent with, or after administration of the daily dose of the dietary supplement.

[0326] It is to be appreciated that the Detailed Description section, and not the Summary and Abstract sections, is intended to be used to interpret the claims. The Summary and Abstract sections may set forth one or more but not all exemplary embodiments of the present invention as contemplated by the inventor(s), and thus, are not intended to limit the present invention and the appended claims in any way.

[0327] The present invention has been described above with the aid of functional building blocks illustrating the implementation of specified functions and relationships thereof. The boundaries of these functional building blocks have been arbitrarily defined herein for the convenience of the description. Alternate boundaries can be defined so long as the specified functions and relationships thereof are appropriately performed.

[0328] The foregoing description of the specific embodiments will so fully reveal the general nature of the invention that others can, by applying knowledge within the skill of the art, readily modify and / or adapt for various applications such specific embodiments, without undue experimentation, without departing from the general concept of the present invention. Therefore, such adaptations and modifications are intended to be within the meaning and range of equivalents of the disclosed embodiments, based on the teaching and guidance presented herein. It is to be understood that the phraseology or terminology herein is for the purpose of description and not of limitation, such that the terminology orphraseology of the present specification is to be interpreted by the skilled artisan in light of the teachings and guidance.

[0329] The breadth and scope of the present invention should not be limited by any of the above-described exemplary embodiments, but should be defined only in accordance with the following claims and their equivalents. Publications cited herein and the materials for which they are cited are specifically incorporated by reference in their entireties.

Claims

WHAT IS CLAIMED IS:

1. A composition comprising (i) a hemp hull fiber, and (ii) a plurality of bacteria, yeast, or both.

2. The composition of claim 1, wherein the hemp hull fiber comprises a cellulose, a hemicellulose, a lignan, a lignin, or a combination thereof.

3. The composition of claim 1 or claim 2, wherein the composition is formulated as a synbiotic composition.

4. The composition of any one of claims 1-3, further comprising N-trans-caffeoyltyramine (NCT) and / or N-trans-feruloyltyramine (NFT).

5. The composition of any one of claims 1-4, wherein the hemp hull fiber comprises less than 2% wt / v N-trans-caffeoyltyramine (NCT) and / or N-trans-feruloyltyramine (NFT).

6. A composition comprising a plurality of bacteria, yeast, or both, and N-trans- caffeoyltyramine (NCT) and / or N-trans-feruloyltyramine (NFT).

7. The composition of any one of claims 1-6, wherein the composition comprises less than 2% wt / v N-trans-caffeoyltyramine (NCT) and / or N-trans-feruloyltyramine (NFT).

8. The composition of any one of claims 1-7, wherein the plurality of bacteria comprises only one species or strain of bacteria.

9. The composition of any one of claims 1-7, wherein the plurality of bacteria comprises two or more species or strains of bacteria.

10. The composition of any one of claims 1-9, wherein the plurality of bacteria comprises bacteria of the genus Lacticaseibacillus (formerly part of the genus Lactobacillus).

11. The composition of any one of claims 1-10, wherein the plurality of bacteria comprises bacteria selected from Lacticaseibacillus rhamnosus. Lacticaseibacillus casei, Lacticaseibacillus paracasei. or a combination thereof.

12. The composition of any one of claims 1-11, wherein the plurality of bacteria does not comprise Blautia producta, Eggerthella lenla. or both.

13. The composition of any one of claims 1-9, wherein the plurality of bacteria comprises bacteria of the genus Enterococcus, Lactobacillus, Bifidobacterium, Lactococcus, Streptococcus, or a combination thereof.

14. The composition of any one of claims 1-9 or 13, wherein the plurality of bacteria comprises bacteria selected from Enterococcus faecalis, Lactobacillus reuteri, Bifidobacterium animalis, Bifidobacterium longum, Lactobacillus helveticus, Lactococcus lactis, Lactobacillus acidophilus, Streptococcus thermophiles, or a combination thereof.

15. The composition of any one of claims 1-9, 13, or 14, wherein the plurality of bacteria comprises bacteria selected from Enterococcus faecalis BAA-2820, Lactobacillus reuteri BAA-2837, Bifidobacterium animalis subsp. Lactis BAA-2848, Bifidobacterium longum BAA-999, Lactobacillus helveticus BAA-2840, Lactococcus lactis subsp. Lactis ATCC 19435, Lactobacillus acidophilus BAA-2832, Streptococcus thermophilus BAA-19258, or a combination thereof.

16. The composition of any one of claims 1-15, wherein the plurality of bacteria comprises spores.

17. The composition of any one of claims 1-15, wherein the plurality of bacteria comprises vegetative cells.

18. The composition of any one of claims 1-17, wherein the plurality of bacteria comprises spores and vegetative cells.

19. The composition of any one of claims 1-18, wherein the plurality of bacteria comprises a polynucleotide encoding an enzyme that catabolizes a cellulose, a hemicellulose, a lignan, or a lignin.

20. The composition of claim 19, wherein the plurality of bacteria comprises recombinant bacteria genetically engineered to comprise the polynucleotide encoding the enzyme that catabolizes the cellulose, hemicellulose, lignan, or the lignin.

21. The composition of any one of claims 1-6, wherein the plurality of yeast comprises only one species or strain of yeast.

22. The composition of any one of claims 1-6, wherein the plurality of yeast comprises two or more species or strains of yeast.

23. The composition of any one of claims 1-6, 21, or 22, wherein the plurality of yeast comprises yeast of the genus Saccharomyces.

24. The composition of any one of claims 1-6 or 21-23, wherein the plurality of yeast comprises Saccharomyces cerevisiae.

25. The composition of any one of claims 1-6 or 21-24, wherein the plurality of yeast comprises Saccharomyces cerevisiae MYA-797.

26. The composition of any one of claims 1-20, wherein the composition comprises (i) the hemp hull fiber, and (ii) the plurality of bacteria.

27. The composition of any one of claims 1-7 and 21-25, wherein the composition comprises (i) the hemp hull fiber, and (ii) the plurality of yeast.

28. The composition of any one of claims 1-5 or 8-27, wherein the hemp hull fiber is an extruded hemp hull fiber.

29. The composition of any one of claims 1-5 or 8-27, wherein the hemp hull fiber is not an extruded hemp hull fiber.

30. The composition of any one of claims 1-5 or 8-29, wherein the hemp hull fiber comprises less than 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, 0.9%, 0.8%, 0.7%, 0.6%, 0.5%, 0.4%, 0.3%, 0.2%, 0.1%, 0.09%, 0.08%, 0.07%, 0.06%, 0.05%, 0.04%, 0.03%, 0.02%, or 0.01% w / w of inulin.

31. The composition of any one of claims 1-5 or 8-29, wherein the hemp hull fiber does not comprise a detectable amount of inulin.

32. The composition of any one of claims 1-5 or 8-31, wherein the hemp hull fiber comprises insoluble fiber.

33. The composition of any one of claims 1-32, wherein the composition is capable of producing one or more of the metabolites listed in Table 1.

34. The composition of any one of claims 1-32, wherein the composition further comprises one or more of the metabolites listed in Table 1.

35. A comestible composition comprising the composition of any one of claims 1-34 and a nutritionally acceptable additive.

36. The comestible composition of claim 35, wherein the nutritionally acceptable additive comprises a prebiotic additive.

37. The comestible composition of claim 36, wherein the prebiotic additive comprises a prebiotic substance not present in the hemp hull fiber.

38. The comestible composition of claim 37, wherein the prebiotic additive comprises a prebiotic substance present in the hemp hull fiber.

39. The comestible composition of any one of claims 35-38, wherein the nutritionally acceptable additive comprises a flavoring agent, an odor masking agent, a coloring agent, a mouthfeel agent, or a combination thereof.

40. The comestible composition of any one of claims 35-39, wherein the comestible composition is in liquid form.

41. The comestible composition of any one of claims 35-39, wherein the comestible composition is in solid form.

42. The comestible composition of claim 41, wherein the comestible composition comprises one or more capsules or tablets.

43. The comestible composition of claim 41, wherein the comestible composition comprises a crisp (e.g., a protein crisp).

44. An oral dosage form comprising the composition of any one of claims 1-34.

45. The oral dosage form of claim 44, wherein the composition comprises a solution, slurry, suspension, or emulsion.

46. The oral dosage form of claim 44, wherein the composition comprises a solid dosage form.

47. The oral dosage form of claim 46, wherein the solid dosage form comprises a powder, a capsule, or a tablet.

48. The oral dosage form of claim 47, comprising two or more capsules or tablets.

49. The oral dosage form of any one of claims 44-48, wherein the oral dosage form is formulated for delivery to the intestines.

50. The oral dosage form of claim 49, comprising an enteric polymer.

51. The composition of any one of claims 1-34, the comestible composition of any one of claims 35-43, or the oral dosage form of any one of claims 44-50, comprising a “Good Source” level of fiber or a “High” level of fiber.

52. The composition, the comestible composition, or the oral dosage form of claim 51, comprising about 2.5 grams to about 4.9 grams of fiber.

53. The composition, the comestible composition, or the oral dosage form of claim 51 or 52, comprising about 2.8 grams of fiber.

54. The composition, the comestible composition, or the oral dosage form of claim 51, comprising about 5 grams or more of fiber.

55. A method of preparing the composition of any one of claims 1-34, the comestible composition of any one of claims 35-43, or the oral dosage form of any one of claims 44- 50, comprising a step of pre-treating the plurality of bacteria.

56. The method of claim 55, wherein the step of pre-treating comprises germinating a plurality of spores.

57. The method of claim 55 or claim 56, wherein the step of pre-treating comprises growing a plurality of bacterial cells to logarithmic phase.

58. A method of preparing the composition of any one of claims 1-34, the comestible composition of any one of claims 35-43, or the oral dosage form of any one of claims 44- 50, comprising growing the plurality of yeast cells to a logarithmic phase.

59. A method of treating or reducing the risk of a disease, disorder, or dysbiosis, of improving gut epithelial barrier integrity, of increasing gut transepithelial electrical resistance (TEER), of increasing gut microbial diversity, of reducing one or more symptoms of gastrointestinal discomfort, of reducing the risk of gastrointestinal discomfort, or of improving gastrointestinal comfort, comprising administering an effective amount of the composition of any one of claims 1-34, the comestible composition of any one of claims 35-43, or the oral dosage form of any one of claims 44- 50 to a subject in need thereof.

60. A method of treating or reducing the risk of a disease, disorder, or dysbiosis, of improving gut epithelial barrier integrity, of increasing gut transepithelial electrical resistance (TEER), of increasing gut microbial diversity, of reducing one or more symptoms of gastrointestinal discomfort, of reducing the risk of gastrointestinal discomfort, or of improving gastrointestinal comfort, comprising administering to a subject in need thereof an effective amount of: a hemp hull fiber comprising a cellulose, a hemicellulose, a lignan, a lignin, or a combination thereof.

61. The method of claim 60, wherein the subject is additionally administered a plurality of bacteria, yeast, or both.

62. The method of claim 61, wherein the hemp hull fiber and the plurality of bacteria, yeast or both are not contained within the same dosage form.

63. The method of claim 61, wherein the hemp hull fiber and the plurality of bacteria, yeast, or both are contained within the same dosage form.

64. The method of any one of claims 59-63, wherein the one or more symptoms of gastrointestinal discomfort is assessed by one or more of: Digestion Associated Quality of Life Questionnaire (DQLQ), PROMIS Belly Pain 5a, PROMIS GI Gas and Bloating 13a, and PROMIS Anxiety 4a.

65. The method of any one of claims 59-64, wherein the one or more symptoms of gastrointestinal discomfort is one or more of abdominal pain, flatulence, bloating, and anxiety.

66. The method of any one of claims 59-65, wherein the one or more symptoms of gastrointestinal discomfort is improved more than the level of improvement observed following administration of a mass of inulin equivalent to the mass of the hemp hull fiber administered to the subject.

67. The method of any one of claims 59-66, wherein the risk of gastrointestinal discomfort is decreased more than the level of decrease observed following administration of a mass of inulin equivalent to the mass of the hemp hull fiber administered to the subject.

68. The method of any one of claims 59-67, wherein the risk of gastrointestinal comfort is improved more than the level of improvement observed following administration of a mass of inulin equivalent to the mass of the hemp hull fiber administered to the subject.

69. A method of increasing the abundance of Lactobacilliaceae in the gut of a subject in need thereof, comprising administering to the subject an effective amount of: a hemp hull fiber comprising a cellulose, a hemicellulose, a lignan, a lignin, or a combination thereof.

70. The method of claim 69, wherein the subject is additionally administered a plurality of bacteria, yeast, or both.

71. The method of claim 70, wherein the hemp hull fiber and the plurality of bacteria, yeast, or both are not contained within the same dosage form.

72. The method of claim 70, wherein the hemp hull fiber and the plurality of bacteria, yeast, or both are contained within the same dosage form.

73. The method of any one of claims 60-68 and 70-72, wherein the plurality of bacteria, yeast, or both further comprises and / or the hemp hull fiber comprises N-trans- caffeoyltyramine (NCT) and / or N-trans-feruloyltyramine (NFT).

74. The method of any one of claims 59-68, wherein the disease, disorder, or dysbiosis is selected from Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH).

75. The method of any one of claims 59-68, wherein the disease, disorder, or dysbiosis is a gastrointestinal disease, disorder, or dysbiosis.

76. The method of claim 75, wherein the gastrointestinal disease, disorder, or dysbiosis is selected from irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), Crohn's disease (CD), ulcerative colitis (UC), celiac disease, necrotizing enterocolitis, indeterminate colitis, chronic colitis, HIV enteropathy, Helicobacter gastritis, NSAID- enteropathy / enteritis, pouchitis, discontinuous or patchy disease, ileal inflammation, extracolonic inflammation, granulomatous inflammation in response to ruptured crypts, aphthous ulcers, transmural inflammation, microscopic colitis, diverticulitis, diversion colitis, short bowel syndrome, GI mucositis, chemotherapy induced mucositis, radiation induced mucositis, or interstitial cystitis.

77. The method of any one of claims 59-76, wherein the abundance of Lactobacillaceae in the gut of the subject is increased following administration.

78. The method of any one of claims 59-77, wherein the abundance of bacteria of the family Enterob acteriaceae in the gut of the subject is not increased following administration.

79. The method of any one of claims 59-78, wherein the concentration of a short-chain fatty acid in the gut of the subject is increased following administration.

80. The method of claim 79, wherein the short-chain fatty acid comprises acetic acid, propanoic acid, or butyric acid.

81. The method of any one of claims 59, 64-68, or 74-80, wherein the composition, the comestible composition, or the oral dosage form is administered as two or more capsules daily.

82. The method of any one of claims 69-81, further comprising: obtaining a fecal sample from the subject, determining the abundance of Lactobacillaceae present in the fecal sample from the subject, and administering the composition to the subject if the abundance of Lactobacillaceae present in the fecal sample from the subject is less than about 0.001%, 0.01%, 0.1%,0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 1.5%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 30%, 35%, 40%, 45%, or 50% relative to the total abundance of bacteria in the fecal sample.

83. The method of any one of claims 69-81, further comprising: obtaining a fecal sample from the subject, determining the abundance of Lactobacillaceae present in the fecal sample from the subject, obtaining a fecal sample from a healthy donor, determining the abundance of Lactobacillaceae present in the fecal sample from the healthy donor, and administering the composition to the subject if the abundance of Lactobacillaceae present in the fecal sample is less than 10% relative to the abundance of Lactobacillaceae present in the fecal sample from the healthy donor.

84. The method of any one of claims 59-81, further comprising: obtaining a fecal sample from the subject, determining the amount of a cellulose, a hemicellulose, a lignin, a lignan, or a combination thereof present in the fecal sample from the subject, obtaining a fecal sample from a healthy donor, determining the amount of the cellulose, the hemicellulose, the lignin, the lignan, or the combination thereof present in the fecal sample from the healthy donor, and administering the composition to the subject if the amount of the cellulose, the hemicellulose, the lignin, the lignan, or the combination thereof present in the fecal sample from the subject is more than the amount of the cellulose, the hemicellulose, the lignan, the lignin, or the combination thereof present in a fecal sample from the healthy donor.

85. The method of any one of claims 59-81, further comprising: obtaining a fecal sample from the subject, determining the amount of a cellulose, a hemicellulose, a lignin, a lignan, or a combination thereof present in the fecal sample from the subject, obtaining a fecal sample from a healthy donor,determining the amount of the cellulose, the hemicellulose, the lignin, the lignan, or the combination thereof present in the fecal sample from the healthy donor, and administering the composition to the subject if the amount of the cellulose, the hemicellulose, the lignin, the lignan, or the combination thereof present in the fecal sample is more than the amount of the cellulose, the hemicellulose, the lignin, the lignan, or the combination thereof present in the fecal sample from the healthy donor.

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