Sharma, Shweta

Objective: To test the effect of physical activity on the gut microbiome and circulating short chain fatty acids among sedentary overweight/obese adults with prediabetes. We hypothesized that randomization to increased physical activity would result in gut microbiome changes. Methods: \We randomized 77 adults with prediabetes and a sedentary lifestyle into one of two groups: 1) Intervention Group: Invited to engage in home-based moderate intensity walking 3x/week for 30 minutes/session in weeks 1-4 and for 45 minutes/session during weeks 5-8 of the 8-week intervention; or 2) Control Group: Maintained habitual physical activity levels. We performed metagenomic sequencing from stool collected at baseline, week 4, and week 8, with short-chain fatty acids (SCFA) measured from serum collected at baseline and week 8. Taxonomic and functional profiling were performed on the metagenomic reads; alpha diversity metrics were subsequently derived. Linear regression assessed the difference in change between the intervention and control groups for alpha-diversity and SCFA levels. Results: We screened 1,533 participants for eligibility and consented 132. Of these, 87 entered the run-in phase and 77 were randomized. Participants were 51.4±8.9 years old, 87.7% female, and 74% non-Hispanic White. Mean fasting glucose was 103.3±13.2 while mean BMI was 34.4±5.7. In comparison to the control group, the intervention group experienced decreased alpha diversity as characterized by Shannon, Richness, and Faith’s diversity indices by week 8 of the intervention (P<0.05). SCFA levels trended towards improvement in the intervention group, but the results were not statistically significant. Functional analysis of KEGG ontologies revealed themes consistent with a microbiome with enhanced metabolic activity and host-relevant metabolic signaling (Figure). Conclusions: Randomization to a walking intervention resulted in modest gut microbiome changes among adults with overweight/obesity and prediabetes.