High-Intensity Interval Training Modulates Gut Microbial Composition in Aging SAMP6 Mice: A Comparative Study with Moderate-Intensity Continuous Exercise

Background: 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. Methods: Thirty-six male SAMP6 and twelve SAMR1 mice (5- and 7-month-old) were assigned to eight groups (n = 6/group). Sedentary controls included age-matched SAMP6 and SAMR1 mice. Seven-month-old SAMP6 mice underwent 8 weeks of treadmill training: 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. Fecal samples were collected post-intervention for 16S rRNA sequencing (V3–V4 region). Results: Sedentary SAMR1 mice exhibited higher alpha diversity than SAMP6 controls, indicating a link between microbial richness and healthy aging. HIIT significantly restructured gut microbiota composition in SAMP6 mice, specifically enriching Akkermansia muciniphila (LDA > 3.7, p = 0.005) and increasing Bacteroidota abundance. Despite this beneficial taxon enrichment, HIIT was associated with reduced overall alpha diversity compared to sedentary groups. Conclusions: High-intensity interval training may offer superior modulation of key gut microbes linked to metabolic health in aging-prone individuals, supporting its potential as a precision exercise strategy for older adults with early metabolic decline.The findings highlight the importance of exercise intensity in shaping gut microbial communities and suggest that HIIT, despite potentially reducing overall alpha diversity, may be particularly effective in enriching beneficial taxa such as Akkermansia muciniphila. This targeted microbial remodeling may underlie the observed improvements in metabolic health and cognitive function in aging mice. Future studies employing fecal microbiota transplantation from exercised SAMP6 donors to germ-free recipients will be critical to establish causality between exercise-induced microbial shifts and host phenotypes.