Exercise is an important lifestyle intervention for mental health, yet the biological mechanisms through which it influences mood-related behaviors remain incompletely understood. In recent years, growing attention has focused on the bidirectional communication between the gut microbiota and the brain. Beyond their roles in digestion and metabolism, gut microorganisms may interact with the central nervous system through immune and inflammatory pathways and by influencing intestinal barrier integrity. However, whether exercise-induced changes in the gut microbiota can independently convey some of the beneficial effects of exercise on depressive-like behaviors remains to be experimentally established.
To investigate this question, a research team from Shanxi College of Medicine, Fenyang Hospital of Shanxi Province, and the First Hospital of Shanxi Medical University conducted a mouse study. The researchers established a model of depressive-like behaviors using chronic unpredictable mild stress (CUMS) and examined behavioral outcomes and gut microbiota changes following swimming exercise. They subsequently transplanted fecal microbiota from exercise-trained donor mice into stressed recipient mice to determine whether exercise-associated microbial communities could transfer some of the beneficial effects.
The results showed that chronic stress was associated with reduced exploratory behavior, anhedonia-like behavior, and increased immobility, alongside alterations in gut microbiota composition. Swimming exercise improved several measures of depressive-like behavior and altered microbial richness, community structure, and the relative abundance of specific bacterial taxa.
A key finding emerged from the fecal microbiota transplantation (FMT) experiment . Stressed mice receiving microbiota from exercise-trained donors showed a significant increase in sucrose preference and reduced immobility in the forced swim and tail suspension tests, indicating improvements in several measures of depressive-like behavior. Histological analyses also revealed reduced neuronal injury in the hippocampal dentate gyrus and improvements in colonic mucosal and intestinal tissue architecture. These findings suggest that exercise-associated changes in the gut microbiota may contribute to the regulation of depressive-like behaviors, rather than simply accompanying behavioral improvements.
Further microbiome analyses indicated that FMT improved gut microbial diversity in recipient mice and shifted community structure toward that observed in control animals. The relative abundance of several bacterial genera also changed, including a decrease in Adlercreutzia and changes in taxa such as Candidatus_Saccharimonas and Alistipes . The researchers then combined microbiota-based functional predictions with gene-expression analyses in hippocampal tissue. Predicted changes in NOD-like receptor-related signaling pathways were accompanied by changes in the expression of inflammation-related molecules. Following FMT, hippocampal expression of inflammatory mediators, including NLRP3 and IL-18, was reduced, suggesting that inflammatory regulation may be involved in the effects associated with exercise-derived microbiota.
The research team considers these findings further experimental support for a potential link among exercise, the gut microbiota, and the gut–brain axis. Beyond documenting an association between exercise and microbial changes, the study used FMT to investigate whether some effects associated with exercise-derived microbiota could be transferred to recipient animals. This provides a basis for further research into the contribution of the gut microbiota to the behavioral benefits of exercise.
However, the findings remain limited to animal experiments. The study involved a relatively small sample, and correlation analyses alone cannot establish a causal relationship between specific bacterial taxa and behavioral improvements. Functional predictions derived from sequencing data also require direct validation. The specific microbial strains or metabolites responsible for the observed effects have not yet been identified, and these findings do not establish that FMT can treat depression in humans.
Future studies will need to identify functionally relevant microbial strains and bioactive metabolites, use more direct mechanistic approaches to clarify the relationship between the microbiota and inflammatory regulation, and investigate how exercise affects the gut microbiota in people with depression. Such research may deepen our understanding of the biological effects of exercise and inform the future development of microbiota-based adjunctive interventions.
ACTA MICROBIOLOGICA SINICA
Exercise-induced restructuring of gut microbiota mitigates depressive-like behaviors: feasibility and therapeutic prospects of microbiota transplantation
4-Oct-2026