ArticleFrontiers in cellular and infection microbiology2026
High-intensity interval training alleviates depressive-like behaviors and is associated with differences in gut microbiota composition and prefrontal LPS-associated inflammatory measures in CUMS rats.
Article in Frontiers in cellular and infection microbiology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Exercise is a safe and effective intervention for improving depressive symptoms, but the effects and related mechanisms of high-intensity interval training (HIIT) remain unclear. Growing evidence suggests that interactions among the gut microbiota, immune-inflammatory responses, and the central nervous system may contribute to the development and progression of depression. This study investigated whether a 4-week HIIT intervention attenuated depressive-like behaviors and explored related differences in gut microbiota composition and prefrontal cortical lipopolysaccharide (LPS)-associated inflammatory measures. Methods: Forty male Sprague-Dawley rats were initially assigned to either the chronic unpredictable mild stress (CUMS) or control conditions. Following CUMS modeling and corresponding control procedures, rats were further allocated to four groups: CUMS_Sed, CUMS_Ex, Con_Sed, and Con_Ex. Exercise groups performed HIIT on motorized treadmills. Depressive-like behaviors were assessed using the sucrose preference test and the open field test, and body weight was monitored longitudinally as a secondary physiological outcome during CUMS exposure. Gut microbiota composition was profiled using 16S rRNA gene sequencing. LPS levels in the prefrontal cortex and ileum, and IL-1β levels in the prefrontal cortex, were measured using enzyme-linked immunosorbent assay, and prefrontal cortical Toll-like receptor 4 ( Results: CUMS induced marked depressive-like behaviors, including reduced sucrose preference and altered open field test performance. HIIT partially attenuated these behavioral alterations. In exploratory microbiota analyses, HIIT-treated CUMS rats differed from sedentary CUMS rats in gut microbial diversity and taxonomic composition and also showed lower prefrontal cortical LPS and IL-1β levels and lower Conclusions: These findings suggest that HIIT-related improvements in depression-related phenotypes were accompanied by attenuation of LPS-associated inflammatory changes in the prefrontal cortex, while exploratory microbiota analyses identified differences in gut microbiota composition. HIIT may represent a promising exercise-based strategy for improving stress-related depressive-like phenotypes.
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