Gut Health Enhancement by Eating Favourable Food

Study Overview
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Brief Summary
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Within the GEEF om je buik study the effect of 8 weeks intervention with either a diet rich in fiber or fermented food on the gut microbiota will be investigated.

Detailed Description
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This study is a randomized controlled trial (RCT) with three intervention groups (high dietary fiber group (HDF), high fermented foods group (HFF), and a control group (CG)). The total duration of the study is 5 months and consists of an 8-week intervention ( 2-week ramp up period with dietary guidelines, followed by 6-week period with dietary guidelines + additional consumption of study products) and a follow-up after 3 months. In total 147 subjects will be included.

Official Title
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Gut Health Enhancement by Eating Favourable Food

Conditions
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Microbial Colonization

Intervention / Treatment
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* Dietary Supplement: WholeFiber
* Dietary Supplement: Kombucha
* Dietary Supplement: Maltodextrin DE19/21


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and Women, aged ≥18 - ≤70 years; Being able to read and speak Dutch; Willing to keep a stable dietary pattern throughout the study, apart from the dietary advice in the study; Having a smartphone compatible with the Lifedata or PocketQ app to fill out the daily questionnaires. Exclusion Criteria: Having a disease or medical condition which can influence the study results such as diabetes, cancer, diagnosed irritable bowel syndrome, renal disease, liver enzyme abnormality, malignant neoplasm, or a history of inflammatory diseases (such as multiple sclerosis, rheumatoid arthritis, and inflammatory bowel disease); Having a history of intestinal surgery that might interfere with study outcomes (this does not include an appendectomy or cholecystectomy); Average dietary fiber intake of ≥18 gram (women) or ≥22 gram (men) per day, according to the fiber screen questionnaire (see F1 questionnaires); More than 3 servings of fermented foods per day as assessed with the fermented food frequency questionnaire (see F1 questionnaires); Having a Body Mass Index (BMI) of ≥ 30 kg/m2 (self-reported); Currently following a strict diet and unwilling or unable to change; for example, a gluten free diet or a crash diet using meal substitutes; Specific food allergies that interfere with dietary intervention (for example, gluten, lactose, etc); Use of prebiotics, probiotics and/or synbiotics (this should be stopped 4 weeks before the start of the study) and use of fiber supplements; Use of antibiotic treatment less than 3 months before start of the study and/or use of antibiotics during the study; Use of medication that can interfere with the study outcomes, as judged by the medical supervisor; Alcoholic use of ≥14 (women) or ≥28 (men) glasses of alcoholic beverages per week; Use of soft or hard drugs (should be stopped at least 4 weeks before start of the study); Being pregnant or lactating; Participation in another clinical trial at the same time; Student or employee working at either Food, Health and Consumer Research from Wageningen Food and Biobased Research, Microbiology at VU, the MLDS, at WholeFiber, Keep Food Simple or at Cidrani; Unable to follow or comply to study rules.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The study applies a randomized, parallel design of 8 weeks (+ follow-up after 3 months)
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fiber arm<br>Subjects receive dietary guidelines, to increase their fiber intake. Additionally, during the last 6 weeks of the intervention period subjects receive a study product containing 8,5 grams fiber per day. Additionally, subjects receive general guidelines about the effect of nutrition on the gut microbiome. | Dietary Supplement: WholeFiber<br>* WholeFiberTM is a product with high levels of prebiotic dietary fibers ( 85%) mainly consisting of inulin, and some pectin, hemi-cellulose and cellulose that is derived from the root vegetable, chicory roots. Fiber guidelines: Subjects receive a booklet with recipes high in fiber. Subjects are recommended to use 2 recipes per day + a snack. Estimated average intake via the recipes in the recipe booklet is 24 grams/day. General guidelines on nutrition and microbiome: Subjects receive a link to a website with general recommendations to positively alter the gut microbiome (website Voedingscentrum and Dutch Digestive Foundation).<br>* Other names: Chicory roots;|
| Experimental: Fermented food arm<br>Subjects receive dietary guidelines, to increase their intake of fermented foods. Additionally, during the last 6 weeks of the intervention period subjects receive a study product of 17 millilitres concentrated kombucha per day. Additionally, subjects receive general guidelines about the effect of nutrition on the gut microbiome. | Dietary Supplement: Kombucha<br>* The kombucha is produced by a minimum three-month long fermentation process. It is a live fermented herbal drink essence, without refined sugar, and an unpasteurized, organic product. Fermented food guidelines: Study participants in the fermented foods arm are asked to use 3 additional servings of fermented food per day, using the fermented food list / recipe booklet. General guidelines on nutrition and microbiome: Subjects receive a link to a website with general recommendations to positively alter the gut microbiome (website Voedingscentrum and Dutch Digestive Foundation).<br>* Other names: Fermented tea;|
| Placebo Comparator: Control<br>Subjects receive general guidelines about the effect of nutrition on the gut microbiome. Additionally, during the last 6 weeks of the intervention period subjects receive a placebo product of 10 grams maltodextrin per day. | Dietary Supplement: Maltodextrin DE19/21<br>* Maltodextrin DE19/21 is a digestible carbohydrate, that is completely digested and does not reach the colon, which makes it a suitable placebo dietary compound and the reason why it is frequently used in comparable studies. General guidelines on nutrition and microbiome: Subjects receive a link to a website with general recommendations to positively alter the gut microbiome (website Voedingscentrum and Dutch Digestive Foundation).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Microbiota diversity | Microbioal richness (ASV) using 16s rRNA | Baseline (week 0) | 
| Microbiota diversity | Microbioal richness (ASV) using 16s rRNA | End ramp-up (week 2) | 
| Microbiota diversity | Microbioal richness (ASV) using 16s rRNA | End intervention (week 8) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gut microbiota composition | 16s rRNA | Baseline (week 0) | 
| Gut microbiota composition | 16s rRNA | End ramp-up (week 2) | 
| Gut microbiota composition | 16s rRNA | End intervention (week 8) | 
| Carbohydrate Active Enzymes (CAZymes) | Relative abundance of CAZymes using shotgun metagenomic sequencing | Baseline (week 0) | 
| Carbohydrate Active Enzymes (CAZymes) | Relative abundance of CAZymes using shotgun metagenomic sequencing | End ramp-up (week 2) | 
| Carbohydrate Active Enzymes (CAZymes) | Relative abundance of CAZymes using shotgun metagenomic sequencing | End intervention (week 8) | 
| 92 inflammatory serum proteins | 92 protein biomarkers proteins associated with inflammatory and immune response processes measured in dried blood spots using the Olink target 96 panels. Expressed as normalized protein expression (NPX). | Baseline (week 0) | 
| 92 inflammatory serum proteins | 92 protein biomarkers proteins associated with inflammatory and immune response processes measured in dried blood spots using the Olink target 96 panels. Expressed as normalized protein expression (NPX). | End ramp-up (week 2) | 
| 92 inflammatory serum proteins | 92 protein biomarkers proteins associated with inflammatory and immune response processes measured in dried blood spots using the Olink target 96 panels. Expressed as normalized protein expression (NPX). | End intervention (week 8) | 
| Dietary intake | Average intake of fiber, fermented foods and macronutrients using the Traqq app | Baseline (week 0) | 
| Dietary intake | Average intake of fiber, fermented foods and macronutrients using the Traqq app | End ramp-up (week 2) | 
| Dietary intake | Average intake of fiber, fermented foods and macronutrients using the Traqq app | End intervention (week 8) | 
| Dietary intake | Average intake of fiber, fermented foods and macronutrients using the Traqq app | End follow-up (5 months) | 
| Gastrointestinal complaints | Likert-point scale (scores 0 - 10), for bloating, flatulence and abdominal pain. A higher score means more bloating, flatulence and abdominal pain. | Daily during intervention (week 0 - week 8) | 
| Stool frequency | Frequency of bowel movement per day | Daily during intervention (week 0 - week 8) | 
| Stool consistency | Consistency per stool, based on Bristol Stool Score (type 1 -7). Scores 1-7. A higher score means more loose / watery stool. | Daily during intervention (week 0 - week 8) | 
| Abundance of Prevotella | Based on a faecal smear image, using MicrobeLink tool from HORAIZON (AI, machine learning). | Baseline (week 0) | 
| Abundance of Prevotella | Based on a faecal smear image, using MicrobeLink tool from HORAIZON (AI, machine learning). | End ramp-up (week 2) | 
| Abundance of Prevotella | Based on a faecal smear image, using MicrobeLink tool from HORAIZON (AI, machine learning). | End intervention (week 8) | 
| Abundance of Bacteroides | Based on a faecal smear image, using MicrobeLink tool from HORAIZON (AI, machine learning). | Baseline (week 0) | 
| Abundance of Bacteroides | Based on a faecal smear image, using MicrobeLink tool from HORAIZON (AI, machine learning). | End ramp-up (week 2) | 
| Abundance of Bacteroides | Based on a faecal smear image, using MicrobeLink tool from HORAIZON (AI, machine learning). | End intervention (week 8) | 
| Ratio of Prevotella/Bacteroides | Based on a faecal smear image, using MicrobeLink tool from HORAIZON (AI, machine learning). | Baseline (week 0) | 
| Ratio of Prevotella/Bacteroides | Based on a faecal smear image, using MicrobeLink tool from HORAIZON (AI, machine learning). | End ramp-up (week 2) | 
| Ratio of Prevotella/Bacteroides | Based on a faecal smear image, using MicrobeLink tool from HORAIZON (AI, machine learning). | End intervention (week 8) | 
| Microbial alpha diversity | Based on a faecal smear image, using MicrobeLink tool from HORAIZON (AI, machine learning). | Baseline (week 0) | 
| Microbial alpha diversity | Based on a faecal smear image, using MicrobeLink tool from HORAIZON (AI, machine learning). | End ramp-up (week 2) | 
| Microbial alpha diversity | Based on a faecal smear image, using MicrobeLink tool from HORAIZON (AI, machine learning). | End intervention (week 8) | 
| Transit time | Using blue dye method (two blue muffins) | Baseline (week 0) | 
| Transit time | Using blue dye method (two blue muffins) | End ramp-up (week 2) | 
| Transit time | Using blue dye method (two blue muffins) | End intervention (week 8) | 
| Sleep quality | Athens insomnia scale. Score range: 0-28 points. Higher score means worse outcome. | Baseline (week 0) | 
| Sleep quality | Athens insomnia scale. Score range: 0-28 points. Higher score indicates worse sleep quality. | End ramp-up (week 2) | 
| Sleep quality | Athens insomnia scale. Score range: 0-28 points. Higher score indicates worse sleep quality. | End intervention (week 8) | 
| Sleep quality | Athens insomnia scale. Score range: 0-28 points. Higher score indicates worse sleep quality. | End follow-up (5 months) | 
| Digestion associated Quality of Life | Digestion associated Quality of Life (DQLQ) questionnaire. Score range: 0-9. Higher score indicates worse digestion associated quality of life. | Baseline (week 0) | 
| Digestion associated Quality of Life | Digestion associated Quality of Life (DQLQ) questionnaire. Score range: 0-9. Higher score indicates worse digestion associated quality of life. | End ramp-up (week 2) | 
| Digestion associated Quality of Life | Digestion associated Quality of Life (DQLQ) questionnaire. Score range: 0-9. Higher score indicates worse digestion associated quality of life. | End intervention (week 8) | 
| Digestion associated Quality of Life | Digestion associated Quality of Life (DQLQ) questionnaire. Score range: 0-9. Higher score indicates worse digestion associated quality of life. | End follow-up (5 months) | 
| Well-being | World Health Organisation (WHO)-Five Well-Being Index (WHO-5) questionnaire. Raw score ranges from 0-25. Final score is calculated by multiplying the raw score by 4. Final score range 0-100. Higher score indicates better well-being. | Baseline (week 0) | 
| Well-being | World Health Organisation (WHO)-Five Well-Being Index (WHO-5) questionnaire. Raw score ranges from 0-25. Final score is calculated by multiplying the raw score by 4. Final score range 0-100. Higher score indicates better well-being. | End ramp-up (week 2) | 
| Well-being | World Health Organisation (WHO)-Five Well-Being Index (WHO-5) questionnaire. Raw score ranges from 0-25. Final score is calculated by multiplying the raw score by 4. Final score range 0-100. Higher score indicates better well-being. | End intervention (week 8) | 
| Well-being | World Health Organisation (WHO)-Five Well-Being Index (WHO-5) questionnaire. Raw score ranges from 0-25. Final score is calculated by multiplying the raw score by 4. Final score range 0-100. Higher score indicates better well-being. | End follow-up (5 months) | 
| Subjective health (perception and awareness) | A 2-item questionnaire, which assesses how healthy participants perceive their own health and diet. Score range: 2 - 14, higher scores mean a higher subjective health | Baseline (week 0) | 
| Subjective health (perception and awareness) | A 2-item questionnaire, which assesses how healthy participants perceive their own health and diet. Score range: 2 - 14, higher scores mean a higher subjective health | End intervention (week 8) | 
| Subjective health (perception and awareness) | A 2-item questionnaire, which assesses how healthy participants perceive their own health and diet. Score range: 2 - 14, higher scores mean a higher subjective health | End follow-up (5 months) | 
| Intention to stay healthy (perception + awareness) | A 3-item questionnaire, which assesses the extent to which participants have the intention to eat healthy. Score range: 3 - 21, higher scores mean more intention to stay healthy | Baseline (week 0) | 
| Intention to stay healthy (perception + awareness) | A 3-item questionnaire, which assesses the extent to which participants have the intention to eat healthy. Score range: 3 - 21, higher scores mean more intention to stay healthy | End intervention (week 8) | 
| Intention to stay healthy (perception + awareness) | A 3-item questionnaire, which assesses the extent to which participants have the intention to eat healthy. Score range: 3 - 21, higher scores mean more intention to stay healthy | End follow-up (5 months) | 
| Dietary intrinsic motivation (perception + awareness) | A validated 6-item questionnaire, which assesses whether someone's motivation to eat healthy comes from within a person. Score range: 6 - 42, higher scores mean a higher intrinsic motivation. | Baseline (week 0) | 
| Dietary intrinsic motivation (perception + awareness) | A validated 6-item questionnaire, which assesses whether someone's motivation to eat healthy comes from within a person. Score range: 6 - 42, higher scores mean a higher intrinsic motivation. | End intervention (week 8) | 
| Dietary intrinsic motivation (perception + awareness) | A validated 6-item questionnaire, which assesses whether someone's motivation to eat healthy comes from within a person. Score range: 6 - 42, higher scores mean a higher intrinsic motivation. | End follow-up (5 months) | 
| Dietary self-efficacy (perception + awareness) | A validated 8-item questionnaire, which assesses the extent to which one feels capable of eating healthy. Score range: 8 - 49, higher scores mean a higher self-efficacy | Baseline (week 0) | 
| Dietary self-efficacy (perception + awareness) | A validated 8-item questionnaire, which assesses the extent to which one feels capable of eating healthy. Score range: 8 - 49, higher scores mean a higher self-efficacy | End intervention (week 8) | 
| Dietary self-efficacy (perception + awareness) | A validated 8-item questionnaire, which assesses the extent to which one feels capable of eating healthy. Score range: 8 - 49, higher scores mean a higher self-efficacy | End follow-up (5 months) | 
| Self-regulation (perception + awareness) | A 5-item questionnaire, which assesses the ability to plan and monitor actions. Score range: 5 - 35, higher scores mean a higher self-regulation | Baseline (week 0) | 
| Self-regulation (perception + awareness) | A 5-item questionnaire, which assesses the ability to plan and monitor actions. Score range: 5 - 35, higher scores mean a higher self-regulation | End intervention (week 8) | 
| Self-regulation (perception + awareness) | A 5-item questionnaire, which assesses the ability to plan and monitor actions. Score range: 5 - 35, higher scores mean a higher self-regulation | End follow-up (5 months) | 
| Subjective knowledge (perception + awareness) | A validated 5-item questionnaire, which assesses how knowledgeable someone feels about nutrition and gut microbiota. Score range: 5 - 35, higher scores mean a higher subjective knowledge | Baseline (week 0) | 
| Subjective knowledge (perception + awareness) | A validated 5-item questionnaire, which assesses how knowledgeable someone feels about nutrition and gut microbiota. Score range: 5 - 35, higher scores mean a higher subjective knowledge | End intervention (week 8) | 
| Subjective knowledge (perception + awareness) | A validated 5-item questionnaire, which assesses how knowledgeable someone feels about nutrition and gut microbiota. Score range: 5 - 35, higher scores mean a higher subjective knowledge | End follow-up (5 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fiber, Fermented food, Immune system, Microbiota