Integrative and quantitative bioenergetics: Design of a study to assess the impact of the gut microbiome on host energy balance

Abstract

The literature is replete with clinical studies that characterize the structure, diversity, and function of the gut microbiome and correlate the results to different disease states, including obesity. Whether the microbiome has a direct impact on obesity has not been established. To address this gap, we asked whether the gut microbiome and its bioenergetics quantitatively change host energy balance. This paper describes the design of a randomized crossover clinical trial that combines outpatient feeding with precisely controlled metabolic phenotyping in an inpatient metabolic ward. The target population was healthy, weight-stable individuals, age 18-45 and with a body mass index ≤30 kg/m². Our primary objective was to determine within-participant differences in energy balance after consuming a control Western Diet versus a Microbiome Enhancer Diet intervention specifically designed to optimize the gut microbiome for positive impacts on host energy balance. We assessed the complete energy-balance equation via whole-room calorimetry, quantified energy intake, fecal energy losses, and methane production. We implemented conditions of tight weight stability and balance between metabolizable energy intake and predicted energy expenditure. We explored key factors that modulate the balance between host and microbial nutrient accessibility by measuring enteroendocrine hormone profiles, appetite/satiety, gut transit and gastric emptying. By integrating these clinical measurements with future bioreactor experiments, gut microbial ecology analysis, and mathematical modeling, our goal is to describe initial cause-and-effect mechanisms of gut microbiome metabolism on host energy balance. Our innovative methods will enable subsequent studies on the interacting roles of diet, the gut microbiome, and human physiology.

Clinicaltrialsgov identifier: NCT02939703. The present study reference can be found here: https://clinicaltrials.gov/ct2/show/NCT02939703.

Keywords: BMI, body mass index; Bioenergetics; COD, chemical oxygen demand; Calorimeter; Chemical oxygen demand; DEXA, dual energy x-ray absorptiometry; EB, energy balance; EE, energy expenditure; EI, energy intake; Energy balance; MFC, mass flow controller; Microbiome; NIST, national institute of standards technology; PEG, polyethylene glycol; RMR, resting metabolic rate; RQ, respiratory quotient; SCFA, short chain fatty acid; SEE, sleep energy expenditure; TDEE, total daily energy expenditure; TEF, thermic effect of food; VAS, visual analog scale; VCH4, volume of methane produced; VCO2, volume of carbon dioxide produced; VO2, volume of oxygen consume; npRQ, non-protein RQ.