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

NCT07180446 | Not Yet Recruiting

• 1 other identifier: Exercise - Gut Microbiome
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

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.

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 Male Participants
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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)
• 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

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

Central Study Contacts

Elisa Marroquin, Ph.D.

CONTACT

469-491-6443; E.Marroquin@tcu.edu

Ryan Porter, Ph.D.

CONTACT

817-257-6868; r.porter@tcu.edu

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: September 18, 2025
• Primary Completion (Estimated): August 10, 2026
• Study Completion (Estimated): August 10, 2026
• Last Updated: September 18, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)