Interactions Between Diet, Microbiome and Abiotic Conditions in the Gut

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Diet, Healthy, Metabolic Disease

Intervention / Treatment
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* Other: 9-days habitual diet


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Other: 9-days habitual diet|9-days study with habitual diet including one standardized breakfast on a single day|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Microbiome, Metabolomics, Nutrition