Clinical trial NCT04804319: Interactions Between Diet, Microbiome and Abiotic Conditions in the Gut
Official title: Towards Personalized Dietary Recommendations Based on the Interaction Between Diet, Microbiome and Abiotic Conditions in the Gut
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Diet, Healthy
Metabolic Disease
Keywords: Microbiome
Metabolomics
Nutrition
Lead sponsor: University of Copenhagen
Sponsor class: OTHER
Collaborators: name: Technical University of Denmark
name: KU Leuven
name: University of Minnesota
First posted: 2021-03-18
Enrollment: 63
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: OTHER
Time perspective: OTHER
Sampling method: PROBABILITY_SAMPLE
Study population: Healthy volunteers

Brief summary: The aim of this study is to explore the interplay between environmental (abiotic) factors in the gut and the gut microbiota composition, diversity and metabolism. 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 is a 9-day trial including 85 healthy adults in age between 18 and 75. The participants will throughout the trial register their dietary intake, gastrointestinal symptoms including stool frequency and Bristol stool scale, physical activity, and medicine and supplements intake. Participants will on day 3 and day 5, respectively, consume sweet corns to estimate intestinal transit time by the time it takes sweet corn to travel through the gastrointestinal system. Furthermore, the participants will collect daily urine and stool samples.

On day 2 and day 9, participants will arrive fasting at the department in the morning and have their anthropometry, breath hydrogen and methane levels measured, and a blood sample will be collected from each participant.

The first visit (day 2) also includes a standardized meal test (rye bread, butter, jam, egg, and yogurt with nuts and berries) and intake of paracetamol (250 mg). Subsequently, the participants will stay at the department for the following 6 hours and have their postprandial breath hydrogen and methane measured and urine collected at specific intervals.

Moreover, a sub-set of the participants will on the first visit (day 2) immediately after intake of the standardized meal swallow a single-use gastrointestinal SmartPill capsule, which will monitor their gastrointestinal pH, transit time, temperature and pressure.

Eligibility criteria: Inclusion Criteria:

* 18.5-30.0 kg/m2 BMI
* Willing to daily collect a urine and stool sample at home and able to store them in their own freezer in a provided containers throughout the 9-days trial
* Willing to eat sweet corn and report corn-intestinal transit time questionnaire
* Willing to record 9 days dietary intake and defecation pattern
* Willing to have blood samples drawn two times
* Owns a device with access to the internet and is willing to use myfood24 platform
* Known ability to tolerate paracetamol and willing to consume ½ paracetamol tablet dissolved in water (250mg)
* Willing to eat rye bread, butter, jam, egg, yoghurt, berries and nuts

Exclusion Criteria:

* Any condition that makes the project responsible researcher to doubt the feasibility of the volunteer´s participation
* Pregnant or lactating women
* Suffering from inflammatory bowel syndrome (IBS), small intestinal bacterial overgrowth (SIBO) or inflammatory bowel diseases (IBD)
* Intake of antibiotics, diarrhea inhibitors and laxatives ˂ 1month
* Current chronic or infectious diseases
* Diagnosis of diabetes
* History of cancer within the past 5 years (except adequately-treated localized basal cell skin cancer or in situ uterine cervical cancer)
* Frequent intake of painkillers or other medication (mild antidepressants and contraceptive pills are allowed)
* Concurrent participation in another trial

Additional exclusion criteria for the SmartPill sub-study:

* 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, anticholinergic agents, narcotic analgetics, nonsteroidal anti-inflammatory drugs)
* Dysphagia

Primary outcomes:
measure: Faecal pH vs gut microbial saccharolytic/proteolytic metabolism
timeFrame: Day 1-9
Secondary outcomes:
measure: Abiotic factors vs faecal metagenomic profile
timeFrame: Day 1-9
measure: Abiotic factors vs faecal metabolome
timeFrame: Day 1-9
measure: Abiotic factors vs urine metabolome
timeFrame: Day 1-9
measure: Abiotic factors vs blood metabolome
timeFrame: Day 2 and 9
measure: Abiotic factors vs microbial-derived metabolites
timeFrame: Day 1-9
measure: Faecal metagenomics profile vs metabolome
timeFrame: Day 1-9
Other outcomes:
measure: Faecal microbiome
timeFrame: Day 1-9
measure: Faecal metabolome
timeFrame: Day 1-9
measure: In vitro metabolic profiling
timeFrame: Day 1-9
measure: Urine metabolome
timeFrame: Day 1-9
measure: Postprandial urine metabolome
timeFrame: Day 2
measure: Food intake markers
timeFrame: Day 2-3 and day 8-9
measure: Blood metabolome
timeFrame: Day 2 and 9
measure: Fasting breath hydrogen and methane
timeFrame: Day 2 and 9
measure: Postprandial breath hydrogen and methane
timeFrame: Day 2
measure: Plasma levels of short chain fatty acids
timeFrame: Day 2 and day 9
measure: Faecal levels of short chain fatty acids
timeFrame: Day 1-9
measure: Intestinal transit time
timeFrame: Day 2-7
measure: Gastric emptying
timeFrame: Day 2
measure: Appetite hormones
timeFrame: Day 2 and 9
measure: Glucose levels
timeFrame: Day 2 and 9
measure: Insulin levels
timeFrame: Day 2 and day 9
measure: C-peptide levels
timeFrame: Day 2 and day 9
measure: HbA1c levels
timeFrame: Day 2 and day 9
measure: Immune system markers
timeFrame: Day 2 and 9
measure: Lipid metabolism
timeFrame: Day 1-9
measure: 9-days dietary intake
timeFrame: Day 1-9
measure: Faecal nitrogen
timeFrame: Day 1-9
measure: Faecal residual carbohydrates
timeFrame: Day 1-9
measure: Faecal energy
timeFrame: Day 1-9
measure: Microbial load assessed by qPCR
timeFrame: Day 1-9
measure: Microbial load assessed by flow cytometry
timeFrame: Day 1-9
measure: Faecal pH
timeFrame: Day 1-9
measure: Faecal redox potential
timeFrame: Day 1-9
measure: Faecal ionic strength
timeFrame: Day 1-9
measure: Faecal water content
timeFrame: Day 1-9
measure: Subjective gastrointestinal symptoms
timeFrame: Day 1-9
measure: Creatinine
timeFrame: Day 2
measure: Intestinal pH
timeFrame: Day 2-7
measure: Intestinal epithelial cell shedding
timeFrame: Day 1-9
Locations:
city: Copenhagen
country: Denmark
facility: University of Copenhagen, Department of Nutrition, Exercise and Sports
Study officials:
References:
citation: Prochazkova N, Laursen MF, La Barbera G, Tsekitsidi E, Jorgensen MS, Rasmussen MA, Raes J, Licht TR, Dragsted LO, Roager HM. Gut physiology and environment explain variations in human gut microbiome composition and metabolism. Nat Microbiol. 2024 Dec;9(12):3210-3225. doi: 10.1038/s41564-024-01856-x. Epub 2024 Nov 27.