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Effects of Changing Intestinal Transit Time on Gut Microbial Composition and Metabolism

Not Applicable
Completed
Conditions
Diet, Healthy
Metabolic Disease
Interventions
Drug: Diet + laxative
Other: Diet only
Registration Number
NCT06022302
Lead Sponsor
University of Copenhagen
Brief Summary

The aim of this study is to investigate how a short versus a long transit time impacts the gut microbiome's response to a high-fiber and a low-fiber diet, respectively. Such insights could help us understand personal responses to diets and be a first step towards personalized dietary recommendations targeting the gut microbiome.

Detailed Description

The study consists of two parallel arms of whole-meal diets, a low-fiber diet, and a high-fiber diet, respectively. Each arm is designed as a cross-over where participants, in random order, are administered a laxative (Movicol) along with the provided diet to shorten their intestinal transit time or simply consume the provided whole-meal diet (control).

The two intervention periods both involve the following:

* One week of run-in where participants consume the provided whole-meal diet.

* One week where participants either consume Movicol with the provided whole-meal diet or simply continue consuming the provided whole-meal diet (control).

Both arms begin with a screening visit and one week where participants consume and record their habitual diets. Subsequently, the first intervention period follows with one visit before and after each of the two weeks (visit 1-3) followed by the second intervention period with one visit before and after each of the two weeks (visit 4-6). The two cross-over periods are split by a washout of at least two weeks.

The study thus runs for approximately 7-8 weeks depending on the length of the washout and consists of seven visits (one screening visit and six regular visits) in total.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
22
Inclusion Criteria
  • 18.5-30.0 kg/m2 BMI
  • Self-reported ≤3.5 spontaneous bowel movements per week
  • 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 eat the foods provided.
  • Owns a smartphone (iOS 11.0 and later or Android 5.0 and up) with access to the internet.
Exclusion Criteria
  • Pregnant or lactating women.
  • Diagnosis of irritable bowel syndrome (IBS), small intestinal bacterial overgrowth (SIBO), inflammatory bowel diseases (IBD), Gastrointestinal obstruction, or Ischemic colitis
  • Diagnosed constipation according to the ROME IV criteria
  • Intake of antibiotics ˂ 1month, or any medication that can affect the outcomes of the study
  • Regular use of diarrhea inhibitors or laxatives
  • Dysphagia
  • Any chronic disease that can affect the outcomes of the study or pose a risk when consuming Movicol
  • Intake of medications potentially altering gastric pH (proton pump inhibitors, histamine receptor antagonists, antacids)
  • Intake of medications potentially altering the gastrointestinal motility (prokinetics, antiemetic agents, anti-cholinergic agents, narcotic analgetics, nonsteroidal anti-inflammatory drugs, and peroral glucocorticoids)
  • Concurrent participation in another trial
  • Any condition that makes the project responsible researcher to doubt the feasibility of the volunteer´s participation

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
High-fiber dietDiet + laxativeThe high-fiber diet will consist of foods rich in dietary fiber such as coarse vegetables, wholegrain bread, and fruits representing a broad range of dietary fibers aiming for ≈40 g of fiber/10 MJ.
High-fiber dietDiet onlyThe high-fiber diet will consist of foods rich in dietary fiber such as coarse vegetables, wholegrain bread, and fruits representing a broad range of dietary fibers aiming for ≈40 g of fiber/10 MJ.
Low-fiber dietDiet + laxativeThe low-fiber diet will consist of foods poor in fiber such as white bread and refined foods aiming for ≈10 g of fiber/10 MJ.
Low-fiber dietDiet onlyThe low-fiber diet will consist of foods poor in fiber such as white bread and refined foods aiming for ≈10 g of fiber/10 MJ.
Primary Outcome Measures
NameTimeMethod
Fecal butyrate over urine p-cresol sulfate ratioFrom visit 1 through to study completion, an average of 7 weeks

Changes in ratio between fecal butyrate (reflecting saccharolytic fermentation) and urine p-cresol sulfate (reflecting proteolytic fermentation) between interventions.

Secondary Outcome Measures
NameTimeMethod
Fecal ammonia concentrationFrom visit 1 through to study completion, an average of 7 weeks

Change in ammonia content between interventions.

Concentration of fasting plasma short-chain fatty acidsFrom visit 1 through to study completion, an average of 7 weeks

Change in concentration of short-chain fatty acids between interventions.

Fasting plasma concentrations of bile acidsFrom visit 1 through to study completion, an average of 7 weeks

Change in concentration of bile acids in fasting blood between interventions.

Fecal metabolome as assessed by untargeted metabolomicsFrom visit 1 through to study completion, an average of 7 weeks

Changes in the fecal metabolome between interventions.

Gut microbiome assessed by 16S amplicon sequencingFrom visit 1 through to study completion, an average of 7 weeks

Changes in gut microbiota composition between interventions.

Fasting breath methane and hydrogen levels in parts per millionFrom visit 1 through to study completion, an average of 7 weeks

Changes in fasting breath methane and hydrogen concentration measured in parts per million (PPM) in exhalations between interventions.

Change in bowel movement frequencyFrom visit 1 through to study completion, an average of 7 weeks

Changes in bowel movement frequency will be measured by the participants recording every bowel movement in a defecation diary during the study.

Whole gut transit time measured by sweet cornFrom visit 1 through to study completion, an average of 7 weeks

Changes in whole gut transit time between interventions determined by the passage time of sweet corn.

Whole gut transit time measured by blue muffinsFrom visit 1 through to study completion, an average of 7 weeks

Changes in whole gut transit time between interventions determined by the passage time of muffins with blue dye.

Stool consistencyFrom visit 1 through to study completion, an average of 7 weeks

Changes in stool consistency determined by Bristol Stool Scale. The Bristol Stool Scale measures stool consistency on a scale from 1-7 with high numbers reflecting loose stool.

Fecal water content in percentage of stool weightFrom visit 1 through to study completion, an average of 7 weeks

Change in fecal water content between interventions.

Fecal concentration of short-chain fatty acidsFrom visit 1 through to study completion, an average of 7 weeks

Change in concentration of short-chain fatty acids between interventions.

Fecal pHFrom visit 1 through to study completion, an average of 7 weeks

Change in fecal pH level between interventions.

Gut microbiome assessed by shotgun sequencingFrom visit 1 through to study completion, an average of 7 weeks

Changes in gut microbiota composition between interventions.

Microbial metabolites in urine from proteolytic fermentation as assessed by mass spectrometryFrom visit 1 through to study completion, an average of 7 weeks

Changes in the urine concentration of metabolites of microbial proteolysis between interventions.

Microbial metabolites in blood from proteolytic fermentation as assessed by mass spectrometryFrom visit 1 through to study completion, an average of 7 weeks

Changes in the blood concentration of metabolites of microbial proteolysis between interventions.

Trial Locations

Locations (1)

University of Copenhagen, Department of Nutrition, Exercise and Sports

🇩🇰

Copenhagen, Denmark

University of Copenhagen, Department of Nutrition, Exercise and Sports
🇩🇰Copenhagen, Denmark
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