[Objective] To investigate the effects of Shouwu Pill (SWW) on physical performance, gut microbiota composition, and bile acid metabolism in the mouse model of doxorubicin (DOXO)-induced premature aging, and to preliminarily explore its potential mechanisms. [Methods] A mouse model of premature aging was established by intraperitoneal injection of DOXO. Mice were randomized into Control, DOXO, DOXO+Shouwu Pill low-dose (SWW-L), and DOXO+Shouwu Pill high-dose (SWW-H) groups. Grip strength test, hanging endurance test, and treadmill exercise test were performed to evaluate physical performance. Gut microbiota composition and diversity were analyzed by 16S rRNA gene sequencing, followed by PICRUSt functional prediction. Fecal bile acid profiling was performed via UHPLC-QQQ-MS. Spearman correlation analysis was further conducted to explore the association between differentially abundant gut microbial taxa and bile acid metabolism. [Results] Compared with the Control group, DOXO-treated mice exhibited increased systemic inflammatory cytokine levels and significantly decreased forelimb grip strength, hanging endurance, and maximal running speed, indicating successful establishment of the premature aging model. SWW treatment significantly reduced systemic inflammation and improved physical performance, with the DOXO+SWW-H group demonstrating greater efficacy than the DOXO+SWW-L group. The results of 16S rRNA gene sequencing revealed that DOXO induced gut microbiota dysbiosis characterized by altered microbial diversity and disrupted microbiota structure, including decreased abundance of Muribaculaceae and increased abundance of opportunistic pathogenic genera such as Desulfovibrio and Helicobacter. SWW treatment partially restored the microbiota structure by increasing the abundance of potentially beneficial bacteria, including Akkermansia, Lactobacillus, Bifidobacterium, and Roseburia. PICRUSt functional prediction indicated significant alterations in bile acid metabolism-related pathways following SWW intervention. Fecal bile acid profiling further demonstrated that DOXO treatment led to the accumulation of several conjugated bile acids, including T-α-MCA and T-β-MCA, accompanied by reduced levels of unconjugated bile acids. SWW intervention significantly lowered the levels of conjugated bile acids and partially restored the levels of unconjugated bile acids. Correlation analysis showed that several beneficial bacteria were positively correlated with unconjugated bile acids but negatively correlated with conjugated bile acids. [Conclusion] SWW ameliorates physical decline and gut microbiota dysbiosis in the mouse model of DOXO-induced premature aging. Its anti-aging effects may be associated with modulation of gut microbiota-related bile acid metabolism and restoration of bile acid homeostasis.
| 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 |