Clinical trial NCT06022302: Effects of Changing Intestinal Transit Time on Gut Microbial Composition and Metabolism
Official title: Effects of Changing Intestinal Transit Time on Gut Microbial Composition and Metabolism During a Dietary Intervention with Low and High Fiber.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Diet, Healthy
Metabolic Disease
Keywords: Microbiome
Metabolomics
Transit time
Nutrition
Dietary fibre
Lead sponsor: University of Copenhagen
Sponsor class: OTHER
Collaborators: name: Technical University of Denmark
name: KU Leuven
name: University of Minnesota
First posted: 2023-09-01
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Overall, there are two parallel arms (low- and high-fiber diet) to which the participants will be randomized with an allocation ratio 1:1. In each arm participants will be exposed to a crossover design where participants in random order will continue on the meal intervention alone (control) or receive Movicol (a laxative) along with the meal intervention to shorten intestinal transit time.
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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

Primary outcomes:
measure: Fecal butyrate over urine p-cresol sulfate ratio
timeFrame: From visit 1 through to study completion, an average of 7 weeks
Secondary outcomes:
measure: Whole gut transit time measured by sweet corn
timeFrame: From visit 1 through to study completion, an average of 7 weeks
measure: Whole gut transit time measured by blue muffins
timeFrame: From visit 1 through to study completion, an average of 7 weeks
measure: Stool consistency
timeFrame: From visit 1 through to study completion, an average of 7 weeks
measure: Change in bowel movement frequency
timeFrame: From visit 1 through to study completion, an average of 7 weeks
measure: Fecal water content in percentage of stool weight
timeFrame: From visit 1 through to study completion, an average of 7 weeks
measure: Fecal concentration of short-chain fatty acids
timeFrame: From visit 1 through to study completion, an average of 7 weeks
measure: Fecal pH
timeFrame: From visit 1 through to study completion, an average of 7 weeks
measure: Fecal ammonia concentration
timeFrame: From visit 1 through to study completion, an average of 7 weeks
measure: Concentration of fasting plasma short-chain fatty acids
timeFrame: From visit 1 through to study completion, an average of 7 weeks
measure: Fasting plasma concentrations of bile acids
timeFrame: From visit 1 through to study completion, an average of 7 weeks
measure: Fasting breath methane and hydrogen levels in parts per million
timeFrame: From visit 1 through to study completion, an average of 7 weeks
measure: Microbial metabolites in urine from proteolytic fermentation as assessed by mass spectrometry
timeFrame: From visit 1 through to study completion, an average of 7 weeks
measure: Microbial metabolites in blood from proteolytic fermentation as assessed by mass spectrometry
timeFrame: From visit 1 through to study completion, an average of 7 weeks
measure: Fecal metabolome as assessed by untargeted metabolomics
timeFrame: From visit 1 through to study completion, an average of 7 weeks
measure: Gut microbiome assessed by shotgun sequencing
timeFrame: From visit 1 through to study completion, an average of 7 weeks
measure: Gut microbiome assessed by 16S amplicon sequencing
timeFrame: From visit 1 through to study completion, an average of 7 weeks
Other outcomes:
measure: Urine metabolome as assessed by untargeted metabolomics
timeFrame: From visit 1 through to study completion, an average of 7 weeks
measure: Blood metabolome as assessed by untargeted metabolomics
timeFrame: From visit 1 through to study completion, an average of 7 weeks
measure: Fecal microbial metabolites of proteolytic fermentation measured by mass spectrometry
timeFrame: From visit 1 through to study completion, an average of 7 weeks
measure: Fecal enzymatic activities
timeFrame: From visit 1 through to study completion, an average of 7 weeks
measure: Fecal residual carbohydrate concentration
timeFrame: From visit 1 through to study completion, an average of 7 weeks
measure: Fecal energy density
timeFrame: From visit 1 through to study completion, an average of 7 weeks
measure: Fecal redox potential measured in mV
timeFrame: From visit 1 through to study completion, an average of 7 weeks
measure: Fecal carbon:nitrogen (C:N) ratio
timeFrame: From visit 1 through to study completion, an average of 7 weeks
measure: Fecal microbial load (cells per gram)
timeFrame: From visit 1 through to study completion, an average of 7 weeks
measure: Fecal calprotectin concentration
timeFrame: From visit 1 through to study completion, an average of 7 weeks
measure: Change in various markers related to glucose metabolism
timeFrame: From visit 1 through to study completion, an average of 7 weeks
measure: Change in various markers related to lipid metabolism
timeFrame: From visit 1 through to study completion, an average of 7 weeks
measure: Change in various markers of inflammation
timeFrame: From visit 1 through to study completion, an average of 7 weeks
measure: Change in various appetite hormones
timeFrame: From visit 1 through to study completion, an average of 7 weeks
measure: Urinary creatinine concentration
timeFrame: From visit 1 through to study completion, an average of 7 weeks
measure: Amylase gene copy number
timeFrame: At visit 1
measure: Change in body weight
timeFrame: From baseline through to study completion, an average of 8 weeks
measure: Measurement of breath hydrogen and methane profiles in parts per million (Area under the curve)
timeFrame: From baseline through to study completion, an average of 8 weeks
measure: Habitual dietary intake
timeFrame: Before each intervention, 6 days in total
measure: Change in self-perceived stress level
timeFrame: At visit 1 and after each intervention
measure: Change in subjective gastrointestinal symptoms
timeFrame: From visit 1 through to study completion, an average of 7 weeks
measure: Physical activity level
timeFrame: At baseline
measure: Change in sleep quality
timeFrame: At visit 1 and after each intervention
Locations:
city: Copenhagen
country: Denmark
facility: University of Copenhagen, Department of Nutrition, Exercise and Sports
Study officials:
References: