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

Not Applicable

Not yet recruiting

• Conditions: Obesity &Amp; Overweight

• Registration Number: NCT07180446
• Lead Sponsor: Texas Christian University

Brief Summary

The goal of this clinical trial is to learn how gut bacteria affect the way the body responds to exercise, especially how the body uses insulin. It also aims to learn if a supplement called sodium butyrate can help people who don't respond well to exercise alone.

The main questions it aims to answer are:

* Does exercise improve how the body uses insulin in male participants who have overweight or obesity?

* Can gut bacteria predict who will benefit most from exercise?

* Does sodium butyrate help improve insulin response in people who don't respond to exercise alone?

Participants will:

* Exercise 5 days a week for 12 weeks under supervision

* Take sodium butyrate (a natural gut health supplement) daily for the last 4 weeks of the program

* Provide blood and stool samples at three points during the study

* Complete health and lifestyle questionnaires

* Get body composition scans (DEXA) before, during, and after the study

This study may help researchers find new ways to personalize exercise plans based on gut health and improve blood sugar control.

Detailed Description

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 males 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 25 male participants between the ages of 18 and 40, who are affiliated with Texas Christian University (students, staff, or faculty) and 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.

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.

Study Timeline

• Status Verified: 2025-09
• Study First Submitted: 2025-09-05
• Study First Submitted QC: 2025-09-11
• Last Update Submitted: 2025-09-11
• Study Start: 2025-09-18
• Study First Posted: 2025-09-18
• Last Update Posted: 2025-09-18
• Primary Completion: 2026-08-10
• Study Completion: 2026-08-10

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: Male
• Target Recruitment: 25

Inclusion Criteria

• Male, aged 18 to 40 years
• BMI ≥ 25.0 kg/m² (classified as overweight or obese)
• Affiliated with TCU (student, staff, or faculty)
• Sedentary lifestyle, defined as:
• Less than 150 minutes/week of moderate-intensity aerobic activity
• Less than 75 minutes/week of vigorous-intensity activity
• Fewer than 1 strength training session/week over the past 6 months
• Willingness to maintain current diet throughout the study
• Able and willing to understand and complete forms in English
• Able to provide informed consent

Exclusion Criteria

• Diagnosis of diabetes or currently prescribed insulin
• Hypertension, defined as:
• A diagnosis of high blood pressure
• Currently taking antihypertensive medication
• Blood pressure ≥130/80 mmHg during screening (Visit 1)
• Regular physical activity as defined in inclusion criteria
• Recent significant weight change (≥5% of body weight lost or gained in the past 3 months)
• Use of antibiotics or probiotics in the past 3 months
• Pregnant or planning pregnancy during the study period
• Currently lactating
• Following a restrictive diet (e.g., vegetarian, vegan, keto, carnivore)
• Taking weight loss medications or supplements (e.g., GLP-1 receptor agonists)
• Smoking or excessive alcohol use (>14 drinks/week for men)
• Participation in another research study (clinical trial or intervention study)
• Contraindications to exercise as determined by the Physical Activity Readiness Questionnaire Plus (PARQ+)
• Inability to understand or complete forms in English

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Change in Insulin Sensitivity (HOMA-IR)	Measured at Baseline (Week 0), Week 8 (pre-supplementation), and Week 12 (post-supplementation)	Fasting blood glucose and insulin levels will be used to calculate the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). This outcome will assess the impact of exercise and sodium butyrate supplementation on insulin sensitivity.

Secondary Outcome Measures

Name	Time	Method
Alpha Diversity	Collected at Baseline (Week 0), Week 8, and Week 12	16S rRNA sequencing of stool samples will be used to evaluate changes in gut microbial alpha diversity in response to exercise and butyrate supplementation.
Lean Mass	Measured at Baseline (Week 0), Week 8, and Week 12	Dual-Energy X-ray Absorptiometry (DEXA) will assess changes in total lean mass (kg)
Bone mineral density	Measured at Baseline (Week 0), Week 8, and Week 12	DEXA will be used to measure bone mineral density (g/cm2)
Fat Mass	Measured at Baseline (Week 0), Week 8, and Week 12	Dexa will be used to measure total fat mass (kg)
Beta diversity	Measured at Baseline (Week 0), Week 8, and Week 12	16S rRNA sequencing of stool samples will be used to evaluate changes in gut microbial beta diversity in response to exercise and butyrate supplementation.
Taxonomic Classification	Measured at Baseline (Week 0), Week 8, and Week 12	16S rRNA sequencing of stool samples will be used to evaluate changes in gut microbial taxonomic composition in response to exercise and butyrate supplementation.

Trial Locations

Locations (1)

Texas Christian University; 🇺🇸 Fort Worth, Texas, United States