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To investigate the protective effect of ursula acid (UA) supplementation on alcoholic liver injury and to clarify the role of gut microbiota through fecal microbiota transplantation (FMT) experiments, as well as to explore the underlying mechanisms.
Eight-week-old C57BL/6 mice were randomly divided into a normal control group, an alcohol model group, and a UA intervention group, with six mice in each group. During the 8-week modeling period, fecal samples from each group were collected daily for the last two weeks to prepare fecal microbiota solutions. After the recipient mice underwent gut-derived bacterial clearance, they were randomly assigned to FMT-control, FMT-model, and FMT-UA groups. Starting from the seventh week, each group received daily gavage of 200 μl of the corresponding fecal microbiota solution for two weeks.Hematoxylin-Eosin (HE) staining was used to observe the histopathological changes in liver tissues of the mice, and colorimetric assays were performed to measure serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bile acid (TBA). The changes in gut microbiota of donor mice were analyzed by 16S rRNA gene sequencing, and Western blotting (WB) was used to detect the expression levels of Foresaid X receptor (FXR) protein in the liver of recipient mice.Statistical analysis was conducted using SPSS 22.0, with a significance level (α) set at 0.05.
Compared to the alcohol model group, UA intervention improved liver injury in mice with alcoholic liver damage, evidenced by a 39.3% reduction in serum ALT activity (P < 0.05) and a 16.7% reduction in AST activity (P < 0.05), while also restoring the diversity of gut microbiota. The liver pathology of recipient mice exhibited changes similar to those of donor mice. Analysis of ALT, AST, and TBA levels in recipient mice revealed that, compared to the FMT-control group, the serum ALT, AST, and TBA levels in the FMT-model group increased by 124%, 47.4%, and 97.5%, respectively (P < 0.05); the FMT-UA group showed significant reductions in ALT, AST, and TBA levels compared to the FMT-model group (P < 0.05). WB results indicated that FXR protein expression in the liver tissue of the FMT-model group was only 17.8% of that in the FMT-control group (P < 0.05); compared to the FMT-model group, the FXR protein expression in the liver of the FXR-UA group increased by 2.09 times (P < 0.05).
UA exhibits a protective effect against alcoholic liver injury in mice, and its mechanism may be associated with the regulation of gut microbiota and the modulation of liver FXR protein expression, thereby maintaining bile acid homeostasis.
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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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