Interactions Between Diet, Microbiome and Abiotic Conditions in the Gut

Metabolic Disease Clinical Trial

— PRIMA  

Official title:

Towards Personalized Dietary Recommendations Based on the Interaction Between Diet, Microbiome and Abiotic Conditions in the Gut

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04804319
• Other study ID #: M237
• Status: Completed
• Start date: April 13, 2021
• Est. completion date: November 29, 2021

Study information

• Verified date: April 2024
• Source: University of Copenhagen
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 61
• Est. completion date: November 29, 2021
• Est. primary completion date: November 29, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Diet, Healthy
• Metabolic Disease
• Metabolic Diseases

Intervention

Other:
• 9-days habitual diet
9-days study with habitual diet including one standardized breakfast on a single day

Locations

Country	Name	City	State
Denmark	University of Copenhagen, Department of Nutrition, Exercise and Sports	Copenhagen

Sponsors (4)

Lead Sponsor	Collaborator
University of Copenhagen	KU Leuven, Technical University of Denmark, University of Minnesota

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Faecal microbiome	Determination of the variation in the intra- and inter-individual microbiomes in all faecal samples collected from day 1 to day 9	Day 1-9
Other	Faecal metabolome	Changes in the faecal metabolome within and between volunteers as determined by untargeted metabolic profiling by liquid chromatography mass spectrometry (LC-MS) of all faecal samples collected from day 1 to day 9	Day 1-9
Other	In vitro metabolic profiling	Metabolic profiling of in vitro microbial communities inoculated by faecal outputs from the study	Day 1-9
Other	Urine metabolome	Changes in the urine metabolome within and between volunteers as determined by untargeted metabolic profiling by LC-MS of all urine samples collected from day 1 to day 9	Day 1-9
Other	Postprandial urine metabolome	Diet- and microbial-derived metabolites from the standardised meal determined by metabolic profiling by LC-MS of postprandial urine samples collected at 30 min, 1 hours, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 6-8 hours, 8-10 hours, 10-24 hours	Day 2
Other	Food intake markers	Food intake biomarkers determined by metabolic profiling by LC-MS of 24-hour urine collection at day 2-3 and day 8-9.	Day 2-3 and day 8-9
Other	Blood metabolome	Changes in the blood metabolome within and between volunteers as determined by untargeted metabolic profiling by LC-MS of fasting blood samples collected at day 2 and day 9	Day 2 and 9
Other	Fasting breath hydrogen and methane	Measurement of fasting breath hydrogen and methane exhalation at day 2 and day 9	Day 2 and 9
Other	Postprandial breath hydrogen and methane	Measurement of fasting and postprandial breath hydrogen and methane exhalation after standardized breakfast (every 30 min until 6 hours post-meal)	Day 2
Other	Plasma levels of short chain fatty acids	Measurement of fasting plasma short-chain fatty acids determined by LC-MS from day 2 and day 9	Day 2 and day 9
Other	Faecal levels of short chain fatty acids	Measurements of short-chain fatty acids in all faecal samples collected from day 1 to day 9 determined by LC-MS	Day 1-9
Other	Intestinal transit time	Whole transit time variation within and between volunteers as determined by the "sweet-corn test". Briefly, participants are instructed to consume sweet corns twice, on day 3 and 5, and to record the times until visible corn excretion on these two occasions, as well as their defecation frequency, and stool consistency during days 1 to 9; Whole transit time variation within and between volunteers as determined by the SmartPill Wireless Motility Capsule in the subgroup; Comparison of the whole intestinal transit time data obtained by the Smartpill Wireless Motility Capsule and results from the sweet-corn test in the subgroup; Small bowel transit time determined by the SmartPill Wireless Motility Capsule in the subgroup; Colonic transit time determined by the SmartPill Wireless Motility Capsule in the subgroup	Day 2-7
Other	Gastric emptying	Fluid gastric emptying time determined by the presence of paracetamol metabolites in postprandial urine samples; Solid gastric emptying time determined by the SmartPill Wireless Motility Capsule in the subgroup	Day 2
Other	Appetite hormones	Determination of different appetite hormones in fasting blood samples at day 2 and day 9 to record baseline values	Day 2 and 9
Other	Glucose levels	Measurements of glucose in fasting blood samples at day 2 and day 9	Day 2 and 9
Other	Insulin levels	Measurement of insulin levels in fasting blood samples at day 2 and day 9	Day 2 and day 9
Other	C-peptide levels	Measurement of C-peptide levels in fasting blood samples at day 2 and day 9	Day 2 and day 9
Other	HbA1c levels	Measurement of HbA1c levels in fasting blood samples at day 2 and day 9	Day 2 and day 9
Other	Immune system markers	Measurements of fasting plasma cytokines, C-reactive protein (CRP), lipopolysaccharides (LPS), lipopolysaccharide binding protein (LPS-BP) at day 2 and day 9 to record baseline values	Day 2 and 9
Other	Lipid metabolism	Determination of bile acids in fasting blood samples at day 2 and day 9 and in all faecal samples from day 1 to day 9 to associate with changes in abiotic factors	Day 1-9
Other	9-days dietary intake	Assessment of dietary intake via myfood24 dietary recalls from day 1 to day 9	Day 1-9
Other	Faecal nitrogen	Assessment of nitrogen in all faecal samples from day 1 to day 9	Day 1-9
Other	Faecal residual carbohydrates	Assessment of residual carbohydrates in all faecal samples from day 1 to day 9	Day 1-9
Other	Faecal energy	Assessment of total energy in all faecal samples from day 1 to day 9	Day 1-9
Other	Microbial load assessed by qPCR	Assessment of microbial load by quantitative PCR in all faecal samples from day 1 to day 9	Day 1-9
Other	Microbial load assessed by flow cytometry	Assessment of microbial cell counts by flow cytometry in all faecal samples from day 1 to day 9	Day 1-9
Other	Faecal pH	Measurements of pH in all faecal samples from day 1 to day 9	Day 1-9
Other	Faecal redox potential	Measurements of redox potential in all faecal samples from day 1 to day 9	Day 1-9
Other	Faecal ionic strength	Measurements of ionic strength (Na+ and K+) in all faecal samples from day 1 to day 9	Day 1-9
Other	Faecal water content	Measurements of water content in all faecal samples from day 1 to day 9	Day 1-9
Other	Subjective gastrointestinal symptoms	Gastrointestinal symptoms reported on a scale from 0 to 10, where 0 means no symptoms and 10 means the worst possible symptoms. The questionnaire includes these symptoms: overall stomach and intestine symptoms, stomachache, flatulence, bloating, constipation, and diarrhea.	Day 1-9
Other	Creatinine	Measurements of urinary levels of creatinine from controlled 6-hour urine collection	Day 2
Other	Intestinal pH	pH measurements throughout the gastrointestinal system determined by the SmartPill Wireless Motility Capsule in the subgroup	Day 2-7
Primary	Faecal pH vs gut microbial saccharolytic/proteolytic metabolism	We test whether faecal pH is positively associated with microbial-derived proteolytic metabolites (i.e. p-cresol sulfate and phenylacetylglutamine) in urine and negatively associated with microbial-derived saccharolytic metabolites in faeces (i.e. acetate, butyrate and propionate)	Day 1-9
Secondary	Abiotic factors vs faecal metagenomic profile	We test whether day-to-day variations in abiotic factors (faecal and/or intestinal pH, faecal redox potential, intestinal transit time and substrate availability) are associated with changes in the faecal microbiome	Day 1-9
Secondary	Abiotic factors vs faecal metabolome	We test whether day-to-day variations in abiotic factors (faecal and/or intestinal pH, faecal redox potential, intestinal transit time and substrate availability) are associated with changes in the faecal metabolome	Day 1-9
Secondary	Abiotic factors vs urine metabolome	We test whether day-to-day variations in abiotic factors (faecal and/or intestinal pH, faecal redox potential, intestinal transit time and substrate availability) are associated with changes in the urine metabolome	Day 1-9
Secondary	Abiotic factors vs blood metabolome	We test whether day-to-day variations in abiotic factors (faecal and/or intestinal pH, faecal redox potential, intestinal transit time and substrate availability) are associated with changes in the blood (serum) metabolome	Day 2 and 9
Secondary	Abiotic factors vs microbial-derived metabolites	We test whether day-to-day variations in abiotic factors (faecal and/or intestinal pH, faecal redox potential, intestinal transit time and substrate availability) are associated with changes in diet-derived microbial metabolites in blood/urine/faeces, including short-chain fatty acids, secondary bile acids, phenolic and indolic compounds, branched-chain fatty acids, trimethylamine N-oxide, hippuric acid, urolithin, and enterolactone	Day 1-9
Secondary	Faecal metagenomics profile vs metabolome	We test whether day-to-day variations in the microbiome are associated with changes in diet-derived microbial metabolites in blood/urine/faeces, including short-chain fatty acids, secondary bile acids, phenolic and indolic compounds, branched-chain fatty acids, trimethylamine N-oxide, hippuric acid, urolithin, and enterolactone	Day 1-9