Gut Health Enhancement by Eating Favourable Food (GEEFomjebuik)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Microbial Colonization
• Intervention / Treatment: Dietary supplement: WholeFiber; Dietary supplement: Kombucha; Dietary supplement: Maltodextrin DE19/21

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 146
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Maartje van den Belt, Msc; Phone Number: 06 1852 0632; Email: maartje.vandenbelt@wur.nl
• Study Contact Backup: Name: Nicole de Wit, PhD; Phone Number: +31317480310; Email: nicole.dewit@wur.nl

Study Locations

• Netherlands
  • Gelderland
    • Wageningen, Gelderland, Netherlands, 6708 WG
      • Stichting Wageningen Research
      • Contact: Nicole de Wit, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fiber arm; 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; 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).; Other Names: Chicory roots
Experimental: Fermented food arm; 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; 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).; Other Names: Fermented tea
Placebo Comparator: Control; 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; 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).

What is the study measuring?

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)
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)
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)
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)
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)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Body Mass Index (BMI)	Weight and height will be combined to report BMI in kg/m^2	Baseline (week 0)
Body Mass Index (BMI)	Weight and height will be combined to report BMI in kg/m^2	End ramp-up (week 2)
Body Mass Index (BMI)	Weight and height will be combined to report BMI in kg/m^2	End intervention (week 8)
Body Mass Index (BMI)	Weight and height will be combined to report BMI in kg/m^2	End follow-up (5 months)

Collaborators and Investigators

• Sponsor: VU University of Amsterdam
• Collaborators: Wageningen University and Research; Maag Lever Darm Stichting; Cidrani; WholeFiber; Keep Food Simple
• Investigators: Principal Investigator: Nicole de Wit, PhD, Wageningen Food and Biobased Research; Principal Investigator: Remco Kort, PhD, VU University of Amsterdam

Publications and helpful links

General Publications

• David LA, Maurice CF, Carmody RN, Gootenberg DB, Button JE, Wolfe BE, Ling AV, Devlin AS, Varma Y, Fischbach MA, Biddinger SB, Dutton RJ, Turnbaugh PJ. Diet rapidly and reproducibly alters the human gut microbiome. Nature. 2014 Jan 23;505(7484):559-63. doi: 10.1038/nature12820. Epub 2013 Dec 11.
• Myhrstad MCW, Tunsjo H, Charnock C, Telle-Hansen VH. Dietary Fiber, Gut Microbiota, and Metabolic Regulation-Current Status in Human Randomized Trials. Nutrients. 2020 Mar 23;12(3):859. doi: 10.3390/nu12030859.
• Stiemsma LT, Nakamura RE, Nguyen JG, Michels KB. Does Consumption of Fermented Foods Modify the Human Gut Microbiota? J Nutr. 2020 Jul 1;150(7):1680-1692. doi: 10.1093/jn/nxaa077.
• Wastyk HC, Fragiadakis GK, Perelman D, Dahan D, Merrill BD, Yu FB, Topf M, Gonzalez CG, Van Treuren W, Han S, Robinson JL, Elias JE, Sonnenburg ED, Gardner CD, Sonnenburg JL. Gut-microbiota-targeted diets modulate human immune status. Cell. 2021 Aug 5;184(16):4137-4153.e14. doi: 10.1016/j.cell.2021.06.019. Epub 2021 Jul 12.

Study record dates

Study Major Dates

• Study Start (Actual): May 22, 2023
• Primary Completion (Actual): November 26, 2023
• Study Completion (Estimated): March 5, 2024

Study Registration Dates

• First Submitted: April 3, 2023
• First Submitted That Met QC Criteria: June 9, 2023
• First Posted (Actual): June 12, 2023

Study Record Updates

• Last Update Posted (Actual): January 10, 2024
• Last Update Submitted That Met QC Criteria: January 9, 2024
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Microbiota; Fiber; Immune system; Fermented food
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Infections; Communicable Diseases
• Other Study ID Numbers: NL83652.028.23

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No