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Metformin demonstrates significant hypoglycemic efficacy, yet its clinical application is limited by gastrointestinal adverse reactions. The integration of Chinese and Western medicine through gut microbiota modulation provides a novel strategy for addressing metformin intolerance. Animal experiments were approved by the Animal Ethics Committee of Beijing Friendship Hospital, Capital Medical University (Approval No.: 23-2043). C57BL/6J mice were fed a high-fat diet (HFD) for 4 weeks, followed by 7 days of high-dose metformin administration (250 mg·kg-1, bid) to establish a diarrhea model (HFDM). Additional groups included a normal chow diet group (NCD), HFD group, and combination group (HFDMB; co-administered baicalin while establishing the mouse model of diarrhea, 100 mg·kg-1, bid). Observations of fecal morphology, diarrhea score, and fecal water content revealed that baicalin alleviated metformin-induced early diarrhea. Full-length 16S rRNA sequencing of fecal samples demonstrated that baicalin reduced the relative abundance of diarrhea-associated bacteria (Shigella sonnei, Enterococcus gallinarum, Enterococcus hirae) while increasing beneficial bacteria (Lactobacillus johnsonii, Ligilactobacillus murinus, Limosilactobacillus reuteri). Targeted bile acid quantification of colonic contents revealed elevated levels of primary bile acids (e.g., TCDCA, TCA) in the HFDM group, which were normalized by baicalin co-treatment. Histopathological analysis of colonic tissues via H&E staining and immunohistochemical labeling of tight junction proteins (ZO-1 and occludin) indicated that baicalin mitigated metformin-induced colonic damage and enhanced tight junction protein expression. In conclusion, this study elucidates that baicalin alleviates metformin-induced early diarrhea by modulating gut microbiota-bile acids-gut barrier, offering a scientifically grounded integrated therapeutic approach for clinical metformin intolerance.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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