Differential gut microbial signatures induced by exercise intensity and mode in aging SAMP6 mice

Abstract

The aging population faces increased risks of metabolic and cognitive decline, with emerging evidence linking gut microbiota to exercise-mediated health benefits. Senescence-accelerated mouse prone 6 (SAMP6) exhibits early aging phenotypes, while senescence-resistant 1 (SAMR1) serves as a healthy control. Thirty-six male SAMP6 and twelve SAMR1 mice (5- and 7-month-old) were assigned to eight groups ( n = 6/group). SAMP6 mice underwent 8 weeks of treadmill training beginning at 5 months of age: low-intensity continuous (12 m/min), moderate-intensity continuous (15 m/min), high-intensity interval training (HIIT; 12/20 m/min), or progressively intensified protocol (12→15 m/min). Fecal samples were collected post-intervention for 16 S rRNA sequencing (V3–V4 region). Alpha diversity, beta diversity, and taxonomic composition were analyzed. Seven-month-old sedentary SAMR1 mice (G4) exhibited higher alpha diversity than age-matched SAMP6 controls (G3), indicating a link between microbial richness and healthy aging. HIIT significantly restructured gut microbiota composition in SAMP6 mice, characterized by enrichment of Eggerthella lenta and Lactobacillus johnsonii , increased Proteobacteria abundance without a reduction in alpha diversity. Low-intensity continuous training was associated with the lowest alpha diversity. Moderate-intensity continuous training (MICT) enriched Faecalibaculum rodentium with milder compositional shifts. Progressively intensified training resulted in a phylum-level profile intermediate between sedentary and HIIT groups. HIIT is associated with distinct compositional shifts in the gut microbiota of aging-prone mice. These findings highlight exercise intensity as a critical determinant of gut microbial ecology and support HIIT as a candidate precision exercise strategy for older adults. Future studies employing fecal microbiota transplantation are necessary to test causality.