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

NCT07180446 | Active Not Recruiting

• 1 other identifier: Exercise - Gut Microbiome
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Obesity &Amp; Overweight

Keywords

Butyrate; Gut Microbiome; Exercise; Cardiovascular; Insulin; Gut Microbiota

Outcome Measures

Primary Outcomes (1)

• Change in Insulin Sensitivity (HOMA-IR)

  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.

  Measured at Baseline (Week 0), Week 8 (pre-supplementation), and Week 12 (post-supplementation)

Secondary Outcomes (6)

• Alpha Diversity

  Collected at Baseline (Week 0), Week 8, and Week 12

• Lean Mass

  Measured at Baseline (Week 0), Week 8, and Week 12

• Bone mineral density

  Measured at Baseline (Week 0), Week 8, and Week 12

• Fat Mass

  Measured at Baseline (Week 0), Week 8, and Week 12

• Beta diversity

  Measured at Baseline (Week 0), Week 8, and Week 12

Other Outcomes (6)

• Prediction Accuracy of AI Models for Exercise Response

  Modeling conducted post-study using baseline, Week 8, and Week 12 data

• Anxiety levels

  Completed at Baseline (Week 0), Week 8, and Week 12

• Depression levels

  Measured at Baseline (Week 0), Week 8, and Week 12

Study Arms (1)

Exercise

EXPERIMENTAL

Participants will undergo a 12-week exercise intervention. During the final 4 weeks, they will additionally receive sodium butyrate supplementation. The model uses repeated measures to assess changes in insulin sensitivity, gut microbiome composition, and body composition before and after the intervention.

Behavioral: Cardiovascular Exercise; Dietary Supplement: Butyrate

Interventions

Cardiovascular Exercise BEHAVIORAL

Participants will complete a 12-week supervised cardiovascular exercise program at the TCU Recreation Center. Exercise will occur 5 days per week, beginning with 30 minutes per session and progressing to 60 minutes. Intensity will start at 50% of estimated maximal heart rate and gradually increase to 80% by week 8, remaining at that level through week 12. Exercise modalities may include treadmill walking/running, rowing, elliptical, or cycling, based on participant preference and fitness level. Certified trainers will supervise all sessions to ensure safety, proper technique, and adherence to the intensity targets. Participants will wear ActiGraph heart rate monitors to verify exercise intensity throughout the intervention.

Exercise

Butyrate DIETARY_SUPPLEMENT

Participants will take a dietary supplement containing sodium butyrate during the final 4 weeks (weeks 8-12) of the 12-week intervention. The supplement will be provided in capsule form, with participants instructed to take six capsules per day-two with each meal. This daily dose is equivalent to 3.6 g of butyric acid, which provides 939 mg of sodium, delivered as sodium butyrate. The supplement is intended to support gut health and potentially enhance insulin sensitivity in individuals who do not respond to exercise alone. Participants will receive a 4-week supply during their 8-week study visit, along with instructions for proper use and monitoring of any side effects.

Exercise

Eligibility Criteria

• Age: 18 Years - 40 Years
• Gender Eligibility Details: Biological Female Participants
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• BMI greater than or equal to 25: A BMI at or greater than 25 classifies an individual as having overweight or obesity, which is the population we are looking for in this study.
• Female individuals with regular menstrual cycles (every 24 to 38 days, per the Cleveland Clinic): For this pilot study, we are limiting participation to female individuals, as our sample size is insufficient to investigate sex differences in gut microbiome interactions, which our prior experience suggests are significant. The menstrual cycle is controlled for as it can affect insulin resistance values, which is one of our main outcome variables.
• Age 18-40 years: Limiting the age range helps reduce age-related variability in metabolism, hormonal profiles, and gut microbiota composition. Adults under 40 are less likely to have comorbidities or take medications that could confound results. This age range also ensures participants can legally consent and likely have the cognitive capacity to understand and comply with study procedures.
• Willingness to maintain current diet: Diet has a strong influence on metabolic and microbiome outcomes. Requiring participants to maintain their habitual diet reduces a major source of variability and allows for clearer attribution of observed effects to the intervention being studied
• Desire/ability to understand and complete forms in English: To ensure informed consent and data accuracy, participants must be able to understand study materials, instructions, and questionnaires.
• Willingness to participate in a 12-week exercise intervention.

You may not qualify if:

• Having diabetes of any kind and/or currently being prescribed insulin: Diabetes significantly alters metabolic processes and gut microbiota, which may confound the outcomes of interest. Insulin therapy can independently affect weight, glucose regulation, and inflammatory status. Excluding individuals with diabetes ensures a more metabolically uniform sample and avoids the need for complex medical monitoring
• Having a diagnosis of high blood pressure, currently taking high blood pressure medications, or having high blood pressure readings during visit 1 ≥130/80 mmHg
• Current participation in regular exercise or participation in the last month (\> 150 minutes of moderate activity, 75 minutes of intense activity, or more than 1 session of strength training per week): Regular physical activity affects weight, metabolism, insulin sensitivity, and gut microbiota. Including only untrained participants minimizes variability and allows a clearer assessment of the study intervention's effects without confounding from exercise-related physiological changes.
• Recent significant weight change (weight loss or gain of ≥10% of body weight in the last 3 months): Substantial recent weight gain or loss may signal underlying health changes, dietary shifts, or medication use that could influence study outcomes. It also complicates baseline comparisons and longitudinal measures. Stable weight ensures physiological stability and data consistency.
• Use of antibiotics or probiotics in the last 3 months: Antibiotics can drastically alter the gut microbiome for weeks to months, and probiotics may modulate microbial composition and metabolic markers. To isolate the effects of the study intervention, participants must have a stable, unaltered baseline microbiota.
• Current pregnancy or planning to become pregnant during the study duration: Pregnancy induces major hormonal, metabolic, and microbiome changes, making it a strong confounder. For safety and scientific clarity, pregnant individuals are excluded to avoid complications and ensure data homogeneity.
• Currently lactating: Lactation also involves significant hormonal and metabolic shifts. These physiological changes could confound outcomes related to metabolism, weight, or microbiota composition.
• Following a vegetarian, vegan, keto, carnivore, intermittent fasting, inconsistent time-restricted feeding, or another restrictive diet: Restrictive diets strongly influence gut microbiota, energy metabolism, and nutrient absorption. Excluding individuals on these diets helps control for dietary variability and standardize the nutritional background of participants.
• Smoking, vaping, or excessive alcohol use (e.g., \>14 drinks/week for men, per CDC guidelines): Tobacco and excessive alcohol use are associated with systemic inflammation, metabolic changes, and altered gut microbiota. Excluding these individuals reduces health-related confounding and protects participant safety
• Inability to understand and/or complete forms in English: Accurate completion of study forms, consent, and assessments is essential for reliable data collection. If forms are only available in English, participants must be proficient to ensure informed consent and study integrity.

Sponsors & Collaborators

• Texas Christian University: lead

Study Sites (1)

Texas Christian University

Fort Worth, Texas, 76008, United States

Location

Related Publications (6)

• Noone J, Mucinski JM, DeLany JP, Sparks LM, Goodpaster BH. Understanding the variation in exercise responses to guide personalized physical activity prescriptions. Cell Metab. 2024 Apr 2;36(4):702-724. doi: 10.1016/j.cmet.2023.12.025. Epub 2024 Jan 22.

  PMID: 38262420 BACKGROUND

• Cleophas MCP, Ratter JM, Bekkering S, Quintin J, Schraa K, Stroes ES, Netea MG, Joosten LAB. Effects of oral butyrate supplementation on inflammatory potential of circulating peripheral blood mononuclear cells in healthy and obese males. Sci Rep. 2019 Jan 28;9(1):775. doi: 10.1038/s41598-018-37246-7.

  PMID: 30692581 BACKGROUND

• Krauze W, Busz N, Pikula W, Maternowska M, Prowans P, Maciejewska-Markiewicz D. Effect of Sodium Butyrate Supplementation on Type 2 Diabetes-Literature Review. Nutrients. 2025 May 22;17(11):1753. doi: 10.3390/nu17111753.

  PMID: 40507022 BACKGROUND

• Liu Y, Wang Y, Ni Y, Cheung CKY, Lam KSL, Wang Y, Xia Z, Ye D, Guo J, Tse MA, Panagiotou G, Xu A. Gut Microbiome Fermentation Determines the Efficacy of Exercise for Diabetes Prevention. Cell Metab. 2020 Jan 7;31(1):77-91.e5. doi: 10.1016/j.cmet.2019.11.001. Epub 2019 Nov 27.

  PMID: 31786155 BACKGROUND

• Boule NG, Weisnagel SJ, Lakka TA, Tremblay A, Bergman RN, Rankinen T, Leon AS, Skinner JS, Wilmore JH, Rao DC, Bouchard C; HERITAGE Family Study. Effects of exercise training on glucose homeostasis: the HERITAGE Family Study. Diabetes Care. 2005 Jan;28(1):108-14. doi: 10.2337/diacare.28.1.108.

  PMID: 15616242 BACKGROUND

• Bohm A, Weigert C, Staiger H, Haring HU. Exercise and diabetes: relevance and causes for response variability. Endocrine. 2016 Mar;51(3):390-401. doi: 10.1007/s12020-015-0792-6. Epub 2015 Dec 7.

  PMID: 26643313 BACKGROUND

MeSH Terms

Conditions

Obesity; Overweight; Motor Activity; Insulin Resistance

Interventions

Butyrates

Condition Hierarchy (Ancestors)

Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Behavior; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases

Intervention Hierarchy (Ancestors)

Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids, Volatile; Fatty Acids; Lipids

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: Interventional Study Model: Type: Interventional (Clinical Trial) Design: Single-group assignment (one-arm study) Model: Pretest-Posttest Design Allocation: Non-randomized Masking: None (Open Label) Primary Purpose: Treatment / Mechanistic Time Perspective: Prospective Study Duration: 12 weeks Intervention Type: Behavioral: Supervised cardiovascular exercise (progressively increasing intensity over 12 weeks) Dietary Supplement: Sodium butyrate (oral capsules, 6 per day, taken during weeks 8-12) Description: Participants will undergo a 12-week exercise intervention. During the final 4 weeks, they will additionally receive sodium butyrate supplementation. The model uses repeated measures to assess changes in insulin sensitivity, gut microbiome composition, and body composition before and after the intervention.

Study Record Dates

• First Submitted: September 5, 2025
• First Posted: September 18, 2025
• Study Start: January 18, 2026
• Primary Completion: June 30, 2026
• Study Completion: June 30, 2026
• Last Updated: May 27, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)