Effect of Nutrition Ingredients on Microbiota Modulation

Study Overview
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Brief Summary
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The objective of this study is to evaluate in healthy volunteers the time-dependent effect of daily consumption for four weeks of six different nutrition ingredients on relative abundance of microbial taxa in fecal samples. Second, the study looks at the time-dependent effect of six different nutrition ingredients on alpha and beta diversity of microbiota in fecal samples. Moreover, the time-dependent effect of six different nutrition ingredients on gastrointestinal symptoms and quality of life will be measured.

Official Title
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A Randomized, Double-blinded, Parallel, Placebo-controlled Pilot Study to Investigate the Effect of Nutrition Ingredients on Microbiota Composition in Healthy Adults

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Dietary Supplement: Vitamin B2
* Dietary Supplement: Vitamin C
* Dietary Supplement: Vitamin B2 + C
* Dietary Supplement: Vitamin A
* Dietary Supplement: Vitamin D3
* Dietary Supplement: Vitamin E
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects willing and able to give written informed consent and to understand, to participate and to comply with the clinical study requirements; Be between 20 and 50 years of age; Has a BMI of between 18.5 - 30 Kg/m2; Has a stable body weight (< 5% change) over the past 3-months; Is in general good health, as determined by the investigator; Willing to avoid consuming dietary supplements, prebiotic, probiotic, dietary or fibre rich supplements within 4 weeks prior to baseline visit, until the end of the study; Willing to avoid liver consumption during the intervention Maintain current level of physical activity; Women of child-bearing potential using a non-hormonal contraceptive (e.g. IUD); Willing to consume the investigational product daily for the duration of the study. Exclusion Criteria: Females are pregnant, lactating or wish to become pregnant during the study. Are hypersensitive to any of the components of the test product; Has taken antibiotics within the previous 3 months; Has a history of drug and/or alcohol abuse at the time of enrolment; Consumes greater than 2 servings/day of alcohol (e.g. >28 g ethanol/day); Is a smoker; Has made any major dietary changes in the past 3 months; Subject is planning a sun or ski holiday over the duration of the study; Planned major changes in life style (i.e. diet, dieting, exercise level, travelling) during the duration of the study; Has an eating disorder; Is vegetarian/vegan diet or has food allergies or other issues with foods that would preclude intake of the study products; Is using fibre supplements or enemas; Has a high fiber diet (i.e. >30 g) based on FFQ; Has an active gastrointestinal disorder or previous gastrointestinal surgery, If taking chronic medications (e.g., anti-hypertensive medications), they must have been taking the product for at least two months prior to screening and agree to maintain the same dosage throughout the study; Has a metabolic, psychiatric, or gastrointestinal disease (i.e., diarrhoea, Crohn's disease, ulcerative colitis, irritable bowel syndrome, diverticulosis, stomach or duodenal ulcers, diabetes, hepatitis, HIV, cancer, etc.), with a history of such diseases; Are severely immunocompromised (HIV positive, transplant patient, on antirejection medications, on a steroid for >30 days, or chemotherapy or radiotherapy within the last year); Experiences alarm features such as weight loss, rectal bleeding, recent change in bowel habit (<3 months) or abdominal pain; Have a malignant disease or any concomitant end-stage organ disease; Individuals who, in the opinion of the investigator, are considered to be poor attendees or unlikely for any reason to be able to comply with the trial; Subjects may not be receiving treatment involving experimental drugs. If the subject has been in a recent experimental trial, these must have been completed not less than 60 days prior to this study.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 50 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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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, double-blind, placebo-controlled, parallel trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vitamin B2<br>Daily dose of 75 mg Vitamin B2 | Dietary Supplement: Vitamin B2<br>* One capsule of 75 mg Vitamin B2 once a day for 4 weeks<br>* Other names: Riboflavin;|
| Experimental: Vitamin C<br>Daily dose of 500 mg Vitamin C | Dietary Supplement: Vitamin C<br>* One capsule of 500 mg Vitamin C once a day for 4 weeks<br>|
| Experimental: Vitamin B2 + C<br>Daily dose of 75 mg Vitamin B2 and 500 mg Vitamin C | Dietary Supplement: Vitamin B2 + C<br>* One capsule of of 75 mg Vitamin B2 plus 500 mg Vitamin C once a day for 4 weeks<br>|
| Experimental: Vitamin A<br>Daily dose of 250 µg Vitamin A | Dietary Supplement: Vitamin A<br>* One capsule of 250 µg Vitamin A once a day for 4 weeks<br>|
| Experimental: Vitamin D3<br>Daily dose of 60 µg Vitamin D3 | Dietary Supplement: Vitamin D3<br>* One capsule of 60 µg Vitamin D3 once a day for 4 weeks<br>* Other names: Cholecalciferol;|
| Experimental: Vitamin E<br>Daily dose of 100 mg Vitamin E | Dietary Supplement: Vitamin E<br>* One capsule of 100 mg Vitamin E once a day for 4 weeks<br>* Other names: alpha-tocopherol;|
| Placebo Comparator: Placebo<br>Daily dose of 575 mg microcrystalline cellulose | Dietary Supplement: Placebo<br>* One capsule of 575 mg microcrystalline cellulose once a day for 4 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relative abundance of microbial taxa in fecal samples as assessed by shotgun profiling based on shotgun sequencing | Changes from baseline in the treatment groups as compared to placebo of relative abundance of microbial taxa (operational taxonomic units) | from baseline to 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Alpha diversity of microbiota in fecal samples as assessed by shotgun profiling based on shotgun sequencing | Changes from baseline in the treatment groups as compared to placebo of alpha diversity assessed with shotgun sequencing (Shannon diversity, Estimated ChaoI index) | from baseline to 4 weeks | 
| Beta diversity of microbiota in fecal samples as assessed by shotgun profiling based on shotgun sequencing | Changes from baseline in the treatment groups as compared to placebo of beta diversity assessed with shotgun sequencing (bray-curtis distance metrics) | from baseline to 4 weeks | 
| Short-chain fatty acids concentrations in fecal samples | Changes from baseline in the treatment groups as compared to placebo of short-chain fatty acids using GC-MS (mM) | from baseline to 4 weeks | 
| Ammonia concentrations in fecal samples | Changes from baseline in the treatment groups as compared to placebo of ammonia concentrations assessed with phenol-hypochlorite method (mg/L) | from baseline to 4 weeks | 
| Cytokines and chemokines in blood | Changes from baseline in the treatment group as compared to placebo of cytokines and chemokines using immune assays (pg/mL) | from baseline to 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Intestinal microbiota