Why Calories Are Not the Same - a Gut Explanation?

NCT06932666 | Completed

• 1 other identifier: M408
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this study is to understand how the gut microbiome influences how much dietary energy humans excrete via feces. This study is based on the hypothesis that levels of methane in exhaled breath represent two different gut microbiome community structures, and therefore influence fecal energy excretion differently. Moreover, this study is assessed in the context of two different diets, both isocaloric and equal in macronutrient composition, but differing in contents of fiber, resistant starch, and large particles; which are hypothesized to impact the gut microbiome differently.

Conditions

Breath Analysis; Diet, Healthy

Keywords

Fecal energy; Metabolizable energy; Breath methane; Gut microbiome; Metabolomics; Dietary fiber; Resistant starch; Food particle size

Outcome Measures

Primary Outcomes (1)

• Total fecal energy excretion (between high- and low-methane producers)

  Differences in total fecal energy excretion, determined as total kilocalories excreted via feces, between low and high methane producers following intake of the two controlled, isocaloric diets.

  During each stool collection period (following each 3-day intervention period)

Secondary Outcomes (14)

• Total fecal energy excretion (between diet A and diet B)

  During each stool collection period (following each 3-day intervention period)

• Fecal energy density

  During each 3-day intervention period and its following stool collection period

• Total fecal weight excreted

  During each 3-day intervention period and its following stool collection period

• Breath hydrogen and methane levels

  During each 3-day intervention period and its following stool collection period

• Whole-gut transit time

  During each 3-day intervention period and its following stool collection period

Other Outcomes (26)

• Gut microbiome-derived metabolites (fecal samples)

  During each 3-day intervention period and its following stool collection period

• Gut microbiome-derived metabolites (urine samples)

  Before and during each 3-day intervention period

• Gut microbiome-derived metabolites (blood samples)

  Right before each 3-day intervention period

Study Arms (2)

High-methane producers

EXPERIMENTAL

Individuals exhaling high levels of methane (median exhaled methane \>= 5 ppm), as measured 3-times daily during the screening period.

Other: Diet A group; Other: Diet B group

Low-methane producers

EXPERIMENTAL

Individuals exhaling low levels of methane (median exhaled methane \< 5 ppm), as measured 3-times daily during the screening period.

Other: Diet A group; Other: Diet B group

Interventions

Diet A group OTHER

Diet high in fiber (\> 40g/10MJ), high in resistant starch (\> 10g/10MJ), and containing large food particles. Diet is provided for 3 full days, consists of three meals per day (breakfast, lunch, and dinner) and in-between meals, and covers 100% of the participants' energy requirements.

High-methane producers; Low-methane producers

Diet B group OTHER

Diet low in fiber (\< 10g/10MJ), low in resistant starch (\< 3g/10MJ) and containing small food particles. Diet is provided for 3 full days, consists of three meals per day (breakfast, lunch, and dinner) and in-between meals, and covers 100% of the participants' energy requirements.

High-methane producers; Low-methane producers

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years old
• BMI:18.5-29.9 kg/m2
• Self-reported regular defecations defined as at least every second day
• Willing to collect urine and stool samples at home and able to temporarily store them in their own freezer in a provided container
• Willing to exclusively eat the food provided
• Owning a smartphone (iOS 11.0 and onwards, or Android 5.0 and onwards) with access to the internet
• Speak and understand Danish or English

You may not qualify if:

• Current pregnancy or lactation
• Following a specific dietary program or diet (e.g., vegetarian, vegan, gluten-free) or unable to consume the food provided
• Diagnosis of small intestinal bacterial overgrowth (SIBO), inflammatory bowel diseases (IBD), gastrointestinal obstruction, or ischemic colitis
• Diagnosed chronic constipation
• Regular use of diarrhea inhibitors or laxatives
• Any chronic disease that can affect the outcomes of the study
• Use of medications potentially altering gastric pH (proton pump inhibitors, histamine receptor antagonists, antacids)
• Use of medications potentially altering the gastro-intestinal motility (prokinetics, antiemetic agents, anticholinergic agents, narcotic analgesics, nonsteroidal anti-inflammatory drugs, peroral glucocorticoids, and GLP-1 related medications such as semaglutide and liraglutide)
• Use of antibiotics, or any medication that can affect any outcomes of the study, within the previous three months
• Concurrent participation in another trial
• Any condition that makes the project responsible and/or the clinical responsible doubt the feasibility of the volunteer's participation

Sponsors & Collaborators

• Wageningen University and Research: collaborator
• University of Copenhagen: lead

Study Sites (1)

University of Copenhagen, Department of Nutrition, Exercise and Sports

Frederiksberg, Capital Region, 1958, Denmark

Location

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: Overall, there are two parallel arms - high- (HMP) and low- (LMP) methane producers, to which the participants are allocated in a ratio 1:1 after a 4-day screening period, where individual levels of methane in exhaled breath are measured multiple times. In both arms, participants undergo two 3-days dietary interventions in a crossover design and separated by a +10-day washout period. Participants are randomized to receiving diet A first or diet B first. These two diets are isocaloric and equal in macronutrient composition, but differ on dietary fiber, resistant starch and food particle size.

Study Record Dates

• First Submitted: April 10, 2025
• First Posted: April 17, 2025
• Study Start: May 15, 2025
• Primary Completion: May 13, 2026
• Study Completion: May 13, 2026
• Last Updated: June 2, 2026

Record last verified: 2026-06

Locations

DK (1)