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[Objective] To investigate whether gut microbiota (GM) reshaped by exercise can ameliorate chronic unpredictable mild stress (CUMS)-induced depressive-like behaviors in mice via fecal microbiota transplantation (FMT), and to explore the underlying mechanisms. [Methods] Twenty SPF-grade male C57BL/6J mice (four weeks old) meeting the experimental criteria were randomly assigned to a control group (CON, n=5), a model group (CUMS, n=10), and an exercise group (SW, n=5). After four weeks of CUMS modeling, mice in the model group were further randomized into a PBS control group (CUMS+PBS, n=5) and an FMT group (CUMS+FMT, n=5). The latter received GM transplants from SW donors, and the experiment lasted for eight weeks. Depressive-like phenotypes were assessed by behavioral tests. GM composition was analyzed by 16S rRNA gene sequencing. Hippocampal and colonic structures were examined by histopathological staining. Hippocampal inflammatory cytokine expression was measured by quantitative real-time PCR (qPCR). Correlation analyses were performed between differential microbial taxa and environmental factors. [Results] Compared with the CON group, the model group exhibited typical depressive-like behaviors and disrupted GM structure, characterized by a decreased Bacteroidota/Bacillota ratio and enrichment of the pro-inflammatory genus Adlercreutzia. The SW group showed increased GM richness (P<0.05) and reversed behavioral abnormalities. After FMT intervention, depressive-like behaviors in recipient mice were markedly alleviated, indicated by an increased sucrose preference rate (P<0.000 1) and reduced immobility time in the forced swim test (P<0.01). Furthermore, hippocampal neuronal injury and colonic barrier disruption were effectively repaired. Microbiota analysis revealed that FMT restored GM diversity in recipients (P<0.01), shifted the microbiota structure toward that of the CON group, significantly reduced the relative abundance of Adlercreutzia, and increased the relative abundance of beneficial genera such as Candidatus_Saccharimonas and Alistipes. From a mechanism perspective, FMT suppressed the CUMS-activated nucleotide-binding and oligomerization domain (NOD)-like receptor signaling pathway and downregulated hippocampal mRNA levels of NOD-like receptor family pyrin domain containing 3 (NLRP3) and interleukin-18 (IL-18) (P<0.01). Correlation analysis further confirmed that the abundance of beneficial genera was positively correlated with positive behavioral indices and negatively correlated with pro-inflammatory cytokine expression. [Conclusion] Exercise can attenuate CUMS-induced depressive-like behaviors by reshaping the GM and inhibiting NOD-like receptor signaling pathway-mediated neuroinflammation, and this protective effect can be effectively transferred via FMT.
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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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