Can Gut Bacteria Predict Who Benefits Most From Exercise? A Gut Supplement to Help Exercise Non-Responders

Overview

Overview: You are invited to participate in a research study. You can join if you are a woman, 18-40 years old, have a BMI \>25, and a regular menstrual cycle (every 24 to 38 days, per the Cleveland Clinic). This study is open to the TCU and non-TCU communities. You cannot join if you: * Have diagnosis of diabetes or take insulin or metformin. * Have either diagnosis of high blood pressure, is currently taking high blood pressure medications, or shows high blood pressure readings during visit 1 ≥130/80 mmHg. * For the past month, have engaged in \>150 min/week of moderate intensity aerobic exercise (brisk walking), \>75 min/week of vigorous-intensity aerobic activity (running, fast cycling), and ≥1 session/week of strength exercising using weights for the past month. * Have lost or gained 10% or more of your body weight in the past 3 months. * Have used antibiotics or probiotics in the past 3 months. * Follow a restrictive diet like vegetarian, vegan, keto, or carnivore. * Take weight loss medications or supplements. * Smoke (including vaping) or drink heavily (more than 8 drinks per week for women, per CDC guidelines). Study Details: This study is being conducted at Texas Christian University, Richel building 256 and 259. The project is sponsored by a Texas Christian University Invests in Scholarship grant. The purpose of this study is to looks at how gut bacteria affect exercise benefits. We want to see if a supplement called butyrate can help people who don't get better insulin response from exercise. Butyrate is a natural substance made by gut bacteria when they break down fiber in your diet. The study lasts 12 weeks, including a 12-week supervised exercise program (30-60 min per day/5 days per week), 4 weeks of taking a butyrate supplement daily (weeks 8 to 12), 3 material pick up visits (10 min each) and 3 lab visits (60 min each). All participants will follow the 12-week exercise intervention and all participants will follow the 4-week supplementation. Participants: You are being asked to take part because you're a woman aged 18-40 with a BMI of 25.0 or higher and have regular menstrual cycle (every 24 to 38 days, per the Cleveland Clinic). You must not have done regular exercise (less than 150 minutes of moderate activity, 75 minutes of intense activity, or 1 session of strength training per week) for the past month and have no recent competitive sports experience. If you decide to be in this study, you will be one of 40 participants in this research study at TCU.

This is a single-arm, interventional study investigating the role of the gut microbiome in mediating the effects of cardiovascular exercise on insulin sensitivity in adult females with overweight or obesity (BMI ≥25). The study also evaluates the effectiveness of sodium butyrate supplementation in enhancing insulin sensitivity among individuals who are otherwise non-responsive to exercise alone. The study will enroll 40 female participants between the ages of 18 and 40, who have been sedentary for at least six months. Exclusion criteria include a diagnosis of diabetes or hypertension, recent weight changes, use of antibiotics, probiotics, or weight loss supplements, and any condition contraindicating safe participation in exercise. Participants will engage in a 12-week supervised cardiovascular exercise program at the TCU Recreation Center. Exercise will progress from 30 to 60 minutes per session, 5 days per week, with intensity increasing from 50% to 80% of estimated maximum heart rate. During weeks 8 through 12, participants will take sodium butyrate (BodyBio; 939 mg sodium/day) in capsule form, dosed at 2 capsules with each meal (6 total/day). Data collection includes: * Stool samples (3 total): collected pre-intervention, at week 8 (pre-supplementation), and at week 12 (post-supplementation), to evaluate changes in gut microbial composition and diversity. * Blood samples (3 total): fasting blood draws at the same three time points to measure glucose and insulin for calculation of HOMA-IR and other insulin sensitivity indices. * Body composition: assessed at three time points using Dual-Energy X-ray Absorptiometry (DEXA) to determine fat mass, lean mass, and bone mineral density. * Questionnaires: validated instruments assessing physical activity, dietary intake, sleep, anxiety, depression, and food cravings. * Blood pressure: at the beginning of the study, and every week during the supplementation phase The primary outcomes include changes in insulin sensitivity and gut microbiota composition across the 12-week intervention. Secondary outcomes include body composition changes and the classification of participants as "responders" or "non-responders" to exercise based on insulin sensitivity improvements. An exploratory objective is to develop predictive models using AI algorithms (e.g., decision trees, random forests, support vector machines, logistic regression) trained on baseline gut microbiota and blood biomarkers to predict individual response to exercise. This study is internally funded by a TCU Innovation Scholars (IS) Grant (\~$20,000), with an in-kind supplement donation valued at $2,000 provided by BodyBio. The study is conducted entirely on the TCU campus and has been approved by the TCU Institutional Review Board (IRB #2025-217). Results from this study aim to advance personalized exercise strategies and contribute to the growing field of precision medicine.