Am J Physiol Gastrointest Liver Physiol. 2026 Feb 3. doi: 10.1152/ajpgi.00354.2025. Online ahead of print.
ABSTRACT
Primary aging associates with an imbalanced gut microbiome and cardiovascular disease (CVD) risk in mice and humans. Strong evidence from clinical and pre-clinical studies supports that habitual physical exercise improves cardiovascular function and intestinal health in adults. Here we tested the hypothesis that exercise training, even when initiated late-in-life, re-establishes a beneficial and cooperative intestinal microbiome to an extent that associates with reduced risk for CVD. At 21-months of age, male C57BL/6 mice started a progressive resistance treadmill-training program 6-days per week (Old+ETR) for 12-weeks. Twenty-one month old (Old) and 4-month old (Adult) male mice remained sedentary. First, reductions in exercise capacity and soleus muscle citrate synthase activity displayed by Old vs. Adult mice were restored in Old+ETR animals. Next, systolic function (fractional shortening, FS), diastolic function (E/A ratio), and overall left-ventricular function (myocardial performance index, MPI) otherwise depressed in Old vs. Adult mice were normalized in Old+ETR animals. Third, elevated trimethylamine (TMA) and TMA N-oxide (TMAO), and heightened inflammatory markers [e.g., interferon (IFN)-g and keratinocyte-derived chemokine (KC)], observed in Old vs. Adult mice were lowered in Old+ETR animals. Importantly, the abundance of beneficial microbial features, including Bacteroides, Muribaculaceae, Parabacteroides, and the Rikenellaceae RC9 gut group, otherwise depressed by aging, was normalized in Old+ETR mice. Finally, the Rikenellaceae RC9 gut group positively correlated with FS, and Parabacteroides negatively correlated with IFN-γ. These findings support that late-in-life exercise training beneficially remodels the gut microbiome to an extent that associates with reduced CVD risk in male mice.
PMID:41632533 | DOI:10.1152/ajpgi.00354.2025