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

R. Demmer, Zachary C. Pope, F. R. Avenido, N. R. Mitchell, Paige F. Richmond Hubbard, Stephen Johnson, Shweta Sharma, Daniel J. McDonough et al.

Diabetes, obesity, and cardiometabolic CARE, 2026

1,533 participants

Abstract

OBJECTIVE: To test the effect of physical activity on the gut microbiome and circulating short chain fatty acids among sedentary adults with prediabetes and overweight/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 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: 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 control, the intervention group experienced decreased alpha diversity as characterized by Shannon, Richness, and Faith’s diversity indices by intervention week 8 (P<0.05).…

How strong is the evidence?

Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 1,533 participants or records.

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