Integrating Quantitative Energetics Determines the Microbiome's Contribution to Energy Balance

NCT02939703 | Completed DMC

• 1 other identifier: TRIMD FH 942699
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

We propose to study the role of the gut microbiome in the development of obesity, and whether we can change the microbiome's contribution to host energy balance through diet. We have created a novel model that explicitly links the effects of microorganisms on human energy balance and modeled weight change, and will use the power of metabolic ward studies to measure small changes in energy absorption, total daily energy expenditure, and/or food intake that affect long-term weight gain or loss. By integrating clinical measurements, bioreactor experiments, and mathematical modeling, we will be able to describe cause-and-effect mechanisms that will enable a quantification of the microbiota's contribution to weight gain and inspire future studies on the interactions of diet, the gut microbiome, and human physiology.

Conditions

Obesity

Keywords

Adipose tissue; calorimetry; energy expenditure; microbiome

Outcome Measures

Primary Outcomes (1)

• The primary endpoint for the protocol is the within-participant difference in fecal energy (via chemical oxygen demand, COD) normalized to the total daily energy intake and to the non-metabolizable marker PEG [COD (kcal) / PEG (g)].

  Comparison within subject of control diet versus microbiome enhancer diet.

  Days 24-29 vs. Days 53-58

Study Arms (2)

Control Western diet

ACTIVE COMPARATOR

Participants will consume a control western diet prepared by our metabolic research kitchen for an outpatient period followed by an inpatient period.

Other: Diet

Microbiome Enhancer diet

EXPERIMENTAL

Participants will consume an experimental microbiome enhancer diet prepared by our metabolic research kitchen for an outpatient period followed by an inpatient period

Other: Diet

Interventions

Diet OTHER

Participants will consume either a Control Western Diet or a Microbiome Enhancer Diet.

Control Western diet; Microbiome Enhancer diet

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Able to communicate meaningfully with the investigator and legally competent to provide informed written consent
• Age 18 - 45 years, inclusive
• Weight stable (+/- 3 kg) during the 6 months prior to enrollment
• BMI ≤ 30 kg/m2

You may not qualify if:

• History or presence of cardiovascular disease (unstable angina, myocardial infarction or coronary revascularization within 6 months, clinically significant abnormalities on EKG, presence of cardiac pacemaker, implanted cardiac defibrillator)
• History of type 1 or type 2 diabetes
• Bleeding disorders
• Acute or chronic infections
• Hepatitis and/or cirrhosis
• Severe asthma or chronic obstructive pulmonary disease
• Renal insufficiency or nephritis
• Thyroid dysfunction (suppressed TSH, elevated TSH if symptomatic, elevated thyroid stimulating hormone (TSH) if asymptomatic)
• Uncontrolled hypertension (BP \>160 mmHg systolic or \>100 mmHg diastolic)
• Prior bariatric surgery
• Inflammatory bowel disease or malabsorption, swallowing disorders, suspected or known strictures, fistulas or physiological/mechanical GI obstruction, history of gastrointestinal surgery, Crohn's disease or diverticulitis
• Participants with strict dietary concerns (e.g. vegetarian or kosher diet, multiple food allergies, or allergies to food we will provide them during the study)
• Current use of polyethylene glycol (e.g. Dulcolax, Miralax, Gavilax)
• Cancer within the last 3 years (except non-melanoma skin cancer or treated cervical carcinoma in situ)
• History of depression within \< 5 years from screening visit or which, in the opinion of a medical investigator, will impact the participant's ability to complete the study

Sponsors & Collaborators

• AdventHealth Translational Research Institute: lead
• Arizona State University: collaborator

Study Sites (1)

Translational Research Institute for Metabolism and Diabetes

Orlando, Florida, 32804, United States

Location

Related Publications (3)

• Igudesman D, Yu G, Dutta T, Carnero EA, Krajmalnik-Brown R, Smith SR, Corbin KD. Global Metabolite Profiling in Feces, Serum, and Urine Yields Insights into Energy Balance Phenotypes Induced by Diet-Driven Microbiome Remodeling. Am J Clin Nutr. 2025 Oct;122(4):1027-1041. doi: 10.1016/j.ajcnut.2025.08.003. Epub 2025 Aug 19.

  PMID: 40835099 DERIVED

• Corbin KD, Carnero EA, Dirks B, Igudesman D, Yi F, Marcus A, Davis TL, Pratley RE, Rittmann BE, Krajmalnik-Brown R, Smith SR. Host-diet-gut microbiome interactions influence human energy balance: a randomized clinical trial. Nat Commun. 2023 May 31;14(1):3161. doi: 10.1038/s41467-023-38778-x.

  PMID: 37258525 DERIVED

• Corbin KD, Krajmalnik-Brown R, Carnero EA, Bock C, Emerson R, Rittmann BE, Marcus AK, Davis T, Dirks B, Ilhan ZE, Champagne C, Smith SR. Integrative and quantitative bioenergetics: Design of a study to assess the impact of the gut microbiome on host energy balance. Contemp Clin Trials Commun. 2020 Aug 19;19:100646. doi: 10.1016/j.conctc.2020.100646. eCollection 2020 Sep.

  PMID: 32875141 DERIVED

Related Links

• Translational Research Institute for Metabolism and Diabetes

MeSH Terms

Conditions

Obesity

Interventions

Diet

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena

Study Officials

• Steven R Smith, MD

  Study Principal Investigator

  PRINCIPAL INVESTIGATOR

• Rosa Krajmalnik-Brown, PhD

  Study Principal Investigator at Arizona State University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 16, 2016
• First Posted: October 20, 2016
• Study Start: June 14, 2017
• Primary Completion: July 20, 2019
• Study Completion: July 23, 2019
• Last Updated: June 30, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)