Bacteroides caccae strain ccfm1556 capable of alleviating diarrhea caused by tyrosine kinase inhibitors

Abstract

The application discloses a Bacteroides stercoris CCFM1556 capable of relieving diarrhea caused by tyrosine kinase inhibitors, and belongs to the technical field of microorganisms and the technical field of medicines. The Bacteroides stercoris CCFM1556 screened by the application can relieve the diarrhea symptoms of animals caused by TKI through multiple dimensions, and the specific performance is as follows: the water-like stool property of rats is significantly improved (the water content and the property score are reduced), the intestinal peristalsis is slowed down to prolong the time of the first black stool and the gastrointestinal transit rate, and the colon tissue damage is significantly protected and repaired. Therefore, the Bacteroides stercoris CCFM1556 has extremely wide application prospects in the development of medicines for assisting in relieving the side effects of antitumor drugs.

Description

Technical Field

[0001] This invention relates to the fields of microbial technology and pharmaceutical technology, specifically to a strain of Bacteroides fecalis CCFM1556 that can alleviate diarrhea caused by tyrosine kinase inhibitors. Background Technology

[0002] Tyrosine kinase inhibitors (TKIs), widely used oral small-molecule targeted drugs, have demonstrated remarkable efficacy in the treatment of various solid tumors, such as non-small cell lung cancer and HER2-positive breast cancer. Taking pyrotinib, a Class 1.1 new drug independently developed in my country, as an example, it significantly improves the prognosis of patients with malignant tumors by blocking the human epidermal growth factor receptor family. However, the extremely high incidence of diarrhea (up to 95%, of which approximately 40% are ≥ grade 3 severe diarrhea) accompanying its remarkable efficacy has become a major clinical concern. Severe diarrhea not only greatly increases the economic and psychological burden on patients but also easily leads to electrolyte imbalances and malnutrition, sometimes forcing the interruption of targeted therapy and causing disease progression.

[0003] According to the World Health Organization (WHO) International Classification of Diseases (ICD-10), routine diarrhea is mostly classified as infectious or functional (such as A09 or K52.9), while diarrhea caused by small molecule targeted anti-tumor drugs such as pyrotinib is strictly defined in clinicopathology as a specific drug-toxic colitis subtype (clinically combined code K52.1 and Y43.3).

[0004] Given the unique pathological characteristics of this disease, namely "drug-targeted toxicity" and "aseptic chemical colitis," existing conventional antidiarrheal or colitis medications have inherent limitations or safety risks. Conventional colitis medications (such as aminosalicylic acids and glucocorticoids) are ineffective in treating this disease. The core pathology of conventional colitis (such as ulcerative colitis, UC, and Crohn's disease CD) is chronic inflammatory infiltration mediated by abnormal activation of the autoimmune system. Conventional treatments for these diseases (such as mesalazine) primarily work by inhibiting immune cell activity and the release of peripheral inflammatory factors. However, the specific drug-toxic colitis caused by TKIs originates from the persistent blockade of core signaling pathways such as EGFR / HER2 on the surface of intestinal epithelial cells by exogenous small molecule drugs, directly leading to excessive apoptosis of intestinal mucosal epithelial cells, microvilli atrophy, and barrier collapse. Conventional colitis drugs cannot compensate for, remodel, or antagonize blocked kinase signaling pathways, nor can they fundamentally repair the damage to intestinal epithelial crypt stem cells under TKI compression. Due to "target mismatch," they cannot achieve the desired therapeutic effect.

[0005] Conventional antidiarrheal medications (such as loperamide) can only passively control symptoms: opioid receptor agonists like loperamide primarily control symptoms by slowing intestinal peristalsis and prolonging the retention time of intestinal contents. Furthermore, high doses can easily trigger rebound constipation and severe abdominal pain. More importantly, they cannot reverse or repair the organic toxicity-induced collapse of the intestinal mucosa. In the state of severe toxic colitis caused by TKIs, forcibly inhibiting intestinal peristalsis can easily lead to the accumulation of large amounts of necrotic and sloughed epithelial cells and inflammatory exudates in the intestinal lumen, significantly increasing the clinical risk of toxic megacolon, intestinal necrosis, and intestinal obstruction.

[0006] Existing broad-spectrum probiotic formulations lack specific targeted therapeutic mechanisms: To date, there is no conclusive evidence to support the routine use of conventional broad-spectrum probiotics during TKI treatment. For example, in clinical practice, the routine use of VSL#3 probiotics in non-small cell lung cancer patients receiving TKI treatment has proven ineffective in reducing diarrhea or improving intestinal mucosal damage. The reason for this is that currently available commercially available conventional probiotic strains (such as traditional Lactobacillus or Bifidobacterium) primarily target general functional microecological imbalances and cannot compensate for the specific metabolic disorders and precise loss of core functional species caused by TKI drugs, lacking clear guidance on the "drug-target-microbiota" interaction mechanism.

[0007] With the development of multi-omics technologies, gut microbiota imbalance has been confirmed as a contributing factor in the development and progression of TKI-related diarrhea. Under the strong disturbance of TKI drugs (such as pyrotinib), certain core functional bacteria in the gut undergo specific clearance or a dramatic decrease in abundance. *Bacteroides fecalis* (…) Bacteroides suffocatus As a core member of the gut microbiota responsible for maintaining homeostasis and participating in the degradation of complex carbohydrates and regulation of host metabolism, its specific protective function under TKI drug disturbance has long been overlooked. Currently, there are no known technical solutions or patents published domestically or internationally for precise targeted replenishment using specific exogenous fecal Bacteroides strains to effectively reverse TKI-induced diarrhea phenotypes. Summary of the Invention

[0008] The technical problem to be solved by the present invention is to provide a specific targeted strain that can alleviate diarrhea caused by tyrosine kinase inhibitors.

[0009] The *Bacteroides fecalis* strain screened in this invention can precisely and efficiently reverse the diarrhea phenotype by reconstructing the balance of the intestinal flora and antagonizing local inflammatory damage in response to TKI-induced specific gastrointestinal toxicity. This provides a novel and safe specific strain solution for addressing the unmet clinical need of TKI-related diarrhea.

[0010] This invention provides a fecal bacterium ( Bacteroides suffocatusCCFM1556, with accession number GDMCC No: 68559, was deposited at the Guangdong Provincial Center for Microbial Culture Collection on July 6, 2026.

[0011] The present invention provides a microbial preparation containing the aforementioned Bacteroides fecalis CCFM1556.

[0012] In one embodiment, the bacterial count of *Bacteroides fecalis* CCFM1556 in the microbial preparation is not less than 1 × 10⁻⁶. 6 CFU / mL or 1×10 6 CFU / g.

[0013] The present invention provides a product containing the aforementioned Bacteroides fecalis CCFM1556 or the aforementioned microbial preparation.

[0014] In one embodiment, the product includes food, medicine, or health products.

[0015] In one embodiment, the medicine further comprises pharmaceutical excipients and / or pharmaceutical carriers.

[0016] In one embodiment, the dosage form of the drug includes granules, blocks, tablets, gels, or liquid formulations.

[0017] In one embodiment, the pharmaceutical carrier includes one or more of the following commonly used in medicine: fillers, adhesives, wetting agents, disintegrants, lubricants, and flavoring agents.

[0018] This invention provides the use of Bacteroides fecalis CCFM1556 or the microbial preparation thereof in the preparation of a medicament for relieving diarrhea caused by specific drug-induced colitis.

[0019] In one embodiment, the fecal Bacteroides CCFM1556 can significantly reduce fecal water content and fecal morphology scores in TKI-diarrhea rats.

[0020] In one embodiment, the fecal Bacteroides CCFM1556 can significantly improve the hypermotility of the gastrointestinal tract in TKI-diarrhea rats, restoring the gastrointestinal propulsion rate to near-normal levels.

[0021] In one embodiment, the fecal Bacteroides CCFM1556 can alleviate the damaged colon in TKI-induced diarrheal rats.

[0022] Beneficial effects: This invention screened a strain of Bacteroides fecalith ( Bacteroides suffocatusCCFM1556, this fecal Bacteroides has the effect of alleviating TKI-induced diarrhea, specifically manifested in: (1) significantly reducing fecal water content in TKI-induced diarrhea rats. (2) significantly reducing fecal characteristics score in TKI-induced diarrhea rats. (3) significantly prolonging the time to excretion of the first black stool in TKI-induced diarrhea rats. (4) significantly prolonging the gastrointestinal transit rate in TKI-induced diarrhea rats. (5) alleviating colonic damage in TKI-induced diarrhea rats.

[0023] Preservation of biological materials A strain of Bacteroides faecium CCFM1556, taxonomically named Bacteroides suffocatus It was deposited on July 6, 2026 at the Guangdong Provincial Center for Microbial Culture Collection, with accession number GDMCC No: 68559, located at 5th Floor, Building 59, No. 100 Xianlie Middle Road, Guangzhou. Attached Figure Description

[0024] Figure 1 The following are dynamic changes in fecal water content of rats in each group at different time points (1, 4, and 7 days) in this embodiment of the invention: (a) blank control group, (b) pyrotinib model group, and (c) pyrotinib + BS group.

[0025] Figure 2 Statistical chart of fecal characteristics scores of rats in each group in this embodiment of the invention.

[0026] Figure 3 (a) Quantitative statistical diagram of gastrointestinal transit rate of rats in each group in the embodiments of the present invention; (b) Representative anatomical diagram of carbon propulsion position in the intestine of rats in the blank control group; (c) Representative anatomical diagram of carbon propulsion position in the intestine of rats in the pyrotinib model group; (d) Representative anatomical diagram of carbon propulsion position in the intestine of rats in the pyrotinib + BS group.

[0027] Figure 4 A statistical chart showing the time required for each group of rats to excrete their first black feces in each embodiment of the present invention.

[0028] Figure 5 Histological images of hematoxylin-eosin (H&E) staining of rat colon sections in the embodiments of the present invention (scale bar = 500 μm): (a) blank control group, (b) pyrotinib model group, (c) pyrotinib + BS group. Detailed Implementation

[0029] To make the objectives, technical solutions, and advantages of the present invention clearer, preferred embodiments of the present invention will be described in detail below with reference to the accompanying drawings. It should be understood that these examples are for illustrative purposes only and are not intended to limit the scope of the invention. In the embodiments, all original reagent materials are commercially available, and experimental methods not specifically specified are conventional methods and conditions well known in the art, or according to the conditions recommended by the instrument manufacturer.

[0030] The culture media involved in the following examples are as follows: Brain heart infusion (BHI) broth medium: tryptone 10.0 g / L, disodium hydrogen phosphate dodecahydrate 2.5 g / L, sodium chloride 5.0 g / L, glucose 2.0 g / L, ox heart extract powder 17.5 g / L; measure 1 L of ultrapure water using a graduated cylinder, stir evenly with a magnetic stirrer, add an appropriate amount of NaOH to adjust the pH to between 6.8 and 7.0, dispense into test tubes or Erlenmeyer flasks, seal with rubber stoppers, sterilize at 115℃ for 20 min, dry in an oven, and store at room temperature.

[0031] BHI agar medium: Add agar to the BHI broth medium at a concentration of 1.5-2%, sterilize at 115℃ for 20 minutes, and then pour 10-15 mL into sterile plates in a laminar flow hood. After drying and solidification, store upside down at 4℃ for subsequent plate coating and counting.

[0032] Example 1: An investigation into the association between gut microbiota and TKI-induced diarrhea This embodiment constructs a fecal microbiota transplantation model based on germ-free rats to explore the association between gut microbiota and diarrhea induced by the tyrosine kinase inhibitor (pyrotinib). The model includes two complementary validation systems: (1) Transplantation of drug-microbe co-fermentation products in vitro: TKI and fecal bacteria of healthy humans were co-fermented in vitro under sterile anaerobic conditions for 24 h. The fermentation liquid was collected and transplanted into germ-free rats by gavage. The aim was to eliminate the interference of host background and directly confirm the relationship between microbes and diarrhea phenotype after drug exposure. (2) Clinical patient sample transplantation: Fecal samples of clinical patients with diarrhea caused by taking TKI drugs were collected, prepared into bacterial suspension, and transplanted into germ-free rats by gavage, in order to reproduce the clinical physiological and pathological state.

[0033] In the experiment, germ-free rats were randomly divided into a control group, a TKI fermentation broth transplantation group (transplantation of in vitro drug-microbe co-fermentation products), and a diarrhea patient microbe transplantation group (transplantation of clinical patient samples).

[0034] Following continuous gavage transplantation, various diarrhea phenotypic indices in rats were measured, and the results are as follows: Compared with their respective control groups, the fecal water content of rats in the TKI fermentation broth transplantation group and the diarrhea patient microbiota transplantation group was significantly increased (reaching [values ​​missing] respectively). p <0.001 and p <0.05), the fecal water content of rats in the TKI fermentation broth transplantation group significantly increased from (61.32±1.09) in the control group to (70.86±0.80); the fecal water content of rats in the fecal microbiota transplantation group of diarrhea patients significantly increased from (67.73±1.04) in the control group to (73.88±1.90), indicating that both transplantation methods can quantitatively induce the pathological phenotype of drug-associated diarrhea with extremely high water content. The defecation frequency of rats in the microbiota transplantation group of diarrhea patients significantly increased from (4.25±0.63) in the control group to (11.25±1.93). p <0.05). Meanwhile, the fecal morphology score of rats in the TKI fermentation broth transplantation group (2.00±0.41) was significantly higher than that in the control group (0.50±0.29). p <0.05, the stool was mostly loose and soft with no fixed shape, and the gastrointestinal transit time was significantly shortened from (368.00±3.00) in the control group to (340.70±2.96). p <0.0001).

[0035] These results indicate that both in vitro fermentation microbiota following TKI exposure and direct transplantation of microbiota from diarrhea patients can stably transmit the diarrhea phenotype in germ-free rats. This confirms that the imbalanced gut microbiota caused by TKI disturbance is associated with TKI-induced diarrhea.

[0036] Example 2: Discovery of Bacteroides feces This embodiment utilizes in vitro microecological simulation combined with metagenomic sequencing technology to precisely identify core-specific symbiotic strains damaged by exposure to tyrosine kinase inhibitors. The specific steps and results are as follows: 1. Construction of in vitro fermentation model and metagenomic sequencing Fecal samples were collected from 6 healthy volunteers (6 in total). After being mixed in an equal proportion, sterile PBS (0.1 mol / L, pH 7.4, containing 1 g / L filtered sterile cysteine) was added at a mass-to-volume ratio of 1:7 for homogenization. The mixture was then centrifuged at 600×g for 5 min. The fecal supernatant was collected and added to mGAM medium at a 10% inoculum concentration and mixed thoroughly. The experiment was divided into a drug-treated group (pyrotinib final concentration 33 μM) and a control group (added an equal volume of physiological saline). Immediately after inoculation, the samples were transferred to an anaerobic workstation for in vitro anaerobic fermentation. Fermentation broth samples were collected after 24 h and immediately placed on ice for 15 min to rapidly terminate the fermentation reaction. Six replicates were performed. After incubation, total microbial DNA was extracted from the fermentation broth and subjected to high-quality metagenomic sequencing analysis.

[0037] 2. LEfSe analysis and mining of core differentially expressed bacteria To precisely identify the specific microbial groups significantly inhibited by TKI, linear discriminant analysis (LEfSe) was employed. LEfSe and LDA scores: Differentially differentiated species were screened using an LDA score threshold greater than 2.0. Results showed that all identified statistically significant marker taxa were enriched in the control group, but showed a general decline in the TKI-treated group. The differentially differentiated bacteria mainly included *Bacteroides coccidioides* (…). Bacteroides suffocatus , p <0.05), Clostridium plasminoides ( Faecalibacterium prausnitzii , p <0.05), Halldman's bacterium ( Holdemanella biformis , p <0.05), Eubacterium dolichum CAG 375 ( p Core species such as <0.05).

[0038] Based on the core deletion characteristics identified through multi-cohort metagenomic screening, this invention focuses on Bacteroides fecalis, which is dominant in the human gut and plays a core regulatory role in maintaining intestinal microecological balance and host metabolic homeostasis. Bacteroides suffocatus To confirm its biological effects, this invention precisely reintroduced this fecal Bacteroides (FAG) into a TKI-induced diarrhea rat model. Bacteroides suffocatus From the dimensions of overall phenotype, intestinal motility and barrier repair, the core application value of this strain in alleviating diarrhea induced by tyrosine kinase inhibitors was systematically evaluated and confirmed.

[0039] Example 3: Effects of fecal Bacteroides CCFM1556 on diarrhea-related indicators in TKI-induced diarrhea rats 1. Experimental strains The strain used in the technical solution of this invention is Bacteroides fecalis CCFM1556.

[0040] 2. Sample collection Fecal samples were collected from healthy individuals and placed in sampling tubes containing 30% glycerol. The samples were then stored in an insulated box with ice packs and brought back to the laboratory. The samples were then quickly placed in a -80°C freezer for separation and screening.

[0041] 3. Isolation and purification of fecal Bacteroides (1) Dilution and plating: Take about 0.5 g of fecal sample and add it to a 10 mL centrifuge tube containing 4.5 mL of physiological saline under sterile conditions to obtain 10 -1 Diluent, repeat the above dilution steps to obtain 10 -2 10 -3 10 -4 10 -5 10 -6 Diluent; (2) Spread culture: Take 100 μL of the above 10 -4 10 -5 10 -6 Three graded dilutions were incubated on Bacteroides fecal microbiota-specific selective medium, spread evenly with a spreader, and incubated at 37°C under anaerobic conditions for 48 h. (3) Primary purification culture: Take the diluted plating plate with a colony count in the range of 30 to 300. Randomly select 10 single colonies of suspected target strains from each sample and perform streaking isolation and purification on the Bacteroides fecal microbiota specific selective medium plate. Repeat the purification 2-3 times until a genetically stable pure culture strain is obtained. After identification, it is named Bacteroides fecal microbiota CCFM1556.

[0042] 4. Preparation of oral bacterial solution Bacteroides fecalis CCFM1556 was cultured in BHI medium under anaerobic conditions at 37°C for 24 h, and passaged 2-3 times. After the culture was completed, the culture was centrifuged at 6000 rpm for 5 min, washed with physiological saline, and then centrifuged again under the same conditions. The culture was then resuspended in physiological saline to obtain the oral bacterial solution.

[0043] 5. Animal Experiment Design Eighteen 6-week-old male SD rats were randomly divided into three groups of six each, as shown in Table 1: control group, model group (Pyrotinib), and Clostridium praosporum intervention group (Pyrotinib+BS).

[0044] Before the start of the animal experiments, all animals underwent a one-week acclimatization period. After the acclimatization period, the Control group received 1 mL of normal saline twice daily by gavage; the Pyrotinib group received 1 mL of pyrotinib (120 mg / kg / day) by gavage, followed by 1 mL of normal saline 30 minutes later; and the Pyrotinib+BS group received 1 mL of pyrotinib (120 mg / kg / day) by gavage, followed by 1 mL of 1×10⁻⁶ mcg / kg / day 30 minutes later. 9 Bacterial solution at CFU / mL. Administered via gavage for 7 consecutive days.

[0045] Table 1. Grouping and treatment methods for animal experiments

[0046] 6. Sample Collection Rat feces were collected daily. On the last day of the experiment, fecal characteristics were scored, and the rats were administered ink by gavage. The time of the first black stool excretion was recorded. The gavage dose was 1 mL per rat. On the evening of the end of the intervention period, the rats were fasted but allowed to drink water. The following afternoon, all rats in each group were administered ink by gavage. Ten minutes after gavage, the rats were anesthetized, and blood was collected from the heart. The abdominal cavity was then opened, the mesentery was separated, and the intestinal segment from the cardia to the ileocecal junction was cut off. The small intestine was gently straightened to avoid tearing the intestinal segment. The length of the stomach and intestinal segment was measured as the "total gastrointestinal length", and the length from the cardia to the ink tip was measured as the "ink propulsion length". The gastrointestinal propulsion rate was calculated.

[0047] 7. Experimental Results This invention systematically evaluated the alleviating and protective effects of Bacteroides feces (BS CCFM1556) on gastrointestinal toxicity induced by tyrosine kinase inhibitors by constructing a pyrotinib-induced rat diarrhea model. The specific results are as follows: like Figure 1 As shown, the fecal water content of the control group rats remained within the normal physiological range on days 1, 4, and 7, stabilizing at (56.98±2.21)%, (54.34±2.83)%, and (53.96±1.07)%, respectively, without significant fluctuations. After intervention with pyrotinib, the fecal water content of the rats showed a significant and continuous upward trend over time, from (54.92±0.83)% on day 1 to a substantial increase to (72.56±1.69)% on day 7, significantly higher than that on day 1. p <0.0001 indicates that the intestinal water reabsorption function of rats is severely impaired. After intervention with fecal Bacteroides CCFM1556, the fecal water content of rats on days 1, 4, and 7 were (55.63±1.28)%, (59.08±1.99)%, and (60.35±3.19)%, respectively, remaining within the normal and stable range, with no statistically significant difference at any time point. p>0.05), effectively reversing the loose stools and water excretion induced by pyrotinib.

[0048] like Figure 2 As shown, compared with the normal control group (0.83±0.17), the model group rats had a significantly higher fecal characteristic score (3.83±0.17) due to severe diarrhea. p <0.0001), and the corresponding fecal characteristic scores are shown in Table 2. After intervention with fecal Bacteroides CCFM1556, the fecal characteristic score of rats in the Pyrotinib+BS group was significantly lower than that in the model group to (2.00±0.26). p <0.0001).

[0049] Table 2 Stool Characteristics Scoring Table

[0050] like Figure 3 As shown, the results of the rat ink propulsion experiment indicated that the gastrointestinal transit rate of the model group rats significantly increased from (26.57±1.98)% in the normal control group to (40.51±2.76)%. p <0.001 indicates that pyrotinib stimulates the intestinal wall, leading to extremely hyperactive gastrointestinal motility. After intervention with fecal Bacteroides CCFM1556, the gastrointestinal transit rate in rats significantly decreased to (24.35±1.14)%. p <0.001).

[0051] like Figure 4 As shown, the time from ingesting ink to excreting the first black feces in the model group rats was significantly shortened to (360.2±0.80) min compared to (375.8±2.87) min in the normal control group. p <0.01%, further confirming the accelerated intestinal transit induced by TKI drugs. After targeted replenishment with fecal Bacteroides CCFM1556, the time to excretion of the first black stool in rats was significantly prolonged to (377.0±3.03) min. p <0.01), returning to levels close to the control group.

[0052] like Figure 5H&E-stained sections of colonic tissue showed that the colonic mucosa of the normal control group (Control) rats was intact, with neat and tightly arranged crypts and no inflammatory infiltration. The colonic tissue of the model group (Pyrotinib) rats showed obvious pathological damage, with deformed and locally atrophied crypt structures, and a certain degree of inflammatory damage or loose structure in the intestinal wall mucosa. In contrast, after intervention with fecal Bacteroides CCFM1556, the colonic pathological morphology of rats was significantly repaired, the epithelial crypts regained their intact and regular arrangement, the histopathological score was significantly improved, and the physical integrity of the mucosal barrier was effectively restored.

[0053] Although the present invention has been disclosed above with reference to preferred embodiments, it is not intended to limit the present invention. Anyone skilled in the art can make various modifications and alterations without departing from the spirit and scope of the present invention. Therefore, the scope of protection of the present invention should be determined by the claims.

Claims

1. A type of fecal Bacteroides ( Bacteroides stercoris CCFM1556 was deposited at the Guangdong Provincial Center for Microbial Culture Collection on July 6, 2026, with accession number GDMCC No: 68559.

2. A microbial preparation containing the Bacteroides fecalis CCFM1556 of claim 1.

3. The microbial preparation as described in claim 2, characterized in that, In the microbial preparation, the bacterial count of Bacteroides fecalis CCFM1556 is not less than 1×10⁻⁶. 6 CFU / mL or 1×10 6 CFU / g.

4. A product containing Bacteroides fecalis CCFM1556 as described in claim 1 or a microbial preparation as described in claim 2 or 3.

5. The product as described in claim 4, characterized in that, The products include food, medicine, or health products.

6. The product as described in claim 5, characterized in that, The drug also contains pharmaceutical excipients and / or pharmaceutical carriers.

7. The product as described in claim 6, characterized in that, The dosage forms of the medicine include granules, blocks, tablets, gels, or liquid preparations.

8. The product as described in claim 7, characterized in that, The pharmaceutical carrier includes one or more of the following commonly used medical fillers, adhesives, wetting agents, disintegrants, lubricants, and flavoring agents.

9. The use of the fecal Bacteroides CCFM1556 of claim 1 or the microbial preparation of claim 2 or 3 in the preparation of a medicine for relieving diarrhea caused by specific drug-induced colitis.

10. The application as described in claim 9, characterized in that, The drug has at least one of the following functions: reducing fecal water content and fecal characteristics score in individuals with diarrhea; improving gastrointestinal propulsion rate in individuals with diarrhea; and improving colonic tissue structure and condition.

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