The Effect of Physical Activity on the Gut Microbiome in Prediabetes: Results From a Randomized Controlled Trial

OBJECTIVE To test the effect of physical activity on the gut microbiome and circulating short-chain fatty acids (SCFAs) among sedentary adults with prediabetes and overweight or obesity. RESEARCH DESIGN AND METHODS In a pilot and feasibility trial, we randomized 77 adults with prediabetes and a sedentary lifestyle into one of two groups: 1) intervention: invited to engage in home-based moderate-intensity walking 3×/week for 30 min/session in weeks 1–4 and for 45 min/session during weeks 5–8 of the 8-week intervention; or 2) control: maintained habitual physical activity levels. We performed metagenomic sequencing from stool collected at baseline, week 4, and week 8, with SCFAs measured from serum collected at baseline and week 8. Taxonomic and functional profiling was performed on the metagenomic reads; α-diversity metrics were subsequently derived. Linear regression assessed the difference in change between the intervention and control groups for α-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 mean (SD) 51.4 (8.9) years old, 87.7% female, and 74% non-Hispanic White. Mean fasting glucose was 103.3 (13.2) mg/dL, while mean BMI was 34.4 (5.7) kg/m2. Compared with the control group, the intervention group experienced decreased α-diversity as characterized by Shannon, Richness, and Faith diversity indices by intervention week 8 (P < 0.05). Changes in SCFA levels were not statistically significant different in intervention versus control. CONCLUSIONS Randomization to a walking intervention resulted in modest gut microbiome changes among adults with overweight or obesity and prediabetes.