Luxembourgish Fiber Cohort

NCT04352231 | Completed

• 1 other identifier: LUX-FICO
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

Brief Summary

Many human populations across the world are deficient in the intake of dietary fiber. This decline in fiber consumption parallels an increase in prevalence of a multitude of diseases (e.g. colorectal cancer, multiple sclerosis). A possible link for this association between dietary changes and the diseases could rest in the trillions of commensal gut microbes that digest dietary fibers, provide energy for colonic cells, and modulate the immune system. However, the molecular mechanisms that link fiber deficiency via the activities of the gut microbiome to various diseases have been poorly understood. The investigators previously showed that, in a mouse model with a defined human gut microbiota, removal of fiber from the diet favors proliferation of bacteria that degrade the gut's protective mucus lining. In the proposed project, the investigators aim to translate our findings from mouse studies to humans using a 2x2 crossover study among healthy adults. Forty participants will be randomly assigned to a low- or high-fiber dietary intervention and then, following a washout period to reverse any changes, switched to the other diet type. By employing longitudinal sampling of stool collections, the investigators envision that participants will exhibit increased abundance and activities of mucolytic bacteria when fed a low-fiber diet. The unique selling point of the proposed study involves setting up high-throughput culture collections of mucus-degrading bacteria, whose abundances and activities will be investigated by sequencing and enzymatic assays in stool. Additionally, the investigators will measure inflammatory markers in blood using CyTOF to assess whether short-term fiber deficiency exerts detectable changes in the host immune function. Thus, the proposed dietary intervention clinical trial will help elucidate the role of fiber deficiency in various chronic diseases.

Conditions

Dietary Fiber; Gastrointestinal Microbiome; Healthy Volunteers

Keywords

Metagenome; Whole Genome Sequencing; Biomarkers; Mucolytic Activity; Mass cytometry; Inflammatory Bowel Diseases

Outcome Measures

Primary Outcomes (1)

• Change in gut microbiota composition across study periods

  Assessment of whether statistically significant shifts in the community composition has occurred will be performed using PERMANOVA on the SILVA-annotated taxonomic output of 16S rRNA gene sequence data from stool taken on the last three days of each intervention. Visual presentation of beta-diversity will be presented using PCoA plots based on weighted and unweighted Unifrac distance measures.

  through study completion, an average of 1 month

Secondary Outcomes (2)

• Change in gut microbiota CAZyme abundance across study periods

  through study completion, an average of 1 month

• Change in gut microbiota mucolytic enzyme activity across study periods

  through study completion, an average of 1 month

Other Outcomes (8)

• Change in fecal acetate levels across study periods

  through study completion, an average of 1 month

• Change in fecal propionate levels across study periods

  through study completion, an average of 1 month

• Change in fecal butyrate levels across study periods

  through study completion, an average of 1 month

Study Arms (2)

High to Low Fiber Diet Intervention

EXPERIMENTAL

Participants receive the high fiber diet intervention first, then undergo a washout period to reverse any changes from the diet before receiving the low fiber diet intervention. A second washout period will follow this diet so that we can track any reversal of diet-linked changes.

Dietary Supplement: High Fiber Diet Intervention; Dietary Supplement: Low Fiber Diet Intervention

Low to High Fiber Diet Intervention

EXPERIMENTAL

Participants receive the low fiber diet intervention first, then undergo a washout period to reverse any changes from the diet before receiving the high fiber diet intervention. A second washout period will follow this diet so that we can track any reversal of diet-linked changes.

Dietary Supplement: High Fiber Diet Intervention; Dietary Supplement: Low Fiber Diet Intervention

Interventions

High Fiber Diet Intervention DIETARY_SUPPLEMENT

Plant-based diet with a targeted quantity of 35 g of dietary fiber per day, from a variety of fiber types. Each meal will be balanced to provide all essential nutrients and portions will be of adequate size to ensure participants are satiated. Participants on both diet interventions will be given multivitamin supplements in order to ensure they are receiving essential vitamins and minerals.

High to Low Fiber Diet Intervention; Low to High Fiber Diet Intervention

Low Fiber Diet Intervention DIETARY_SUPPLEMENT

Animal based diet (meat, dairy) with a targeted quantity of 10 g of dietary fiber per day. Each meal will be balanced to provide all essential nutrients and portions will be of adequate size to ensure participants are satiated. Participants on both diet interventions will be given multivitamin supplements in order to ensure they are receiving essential vitamins and minerals.

High to Low Fiber Diet Intervention; Low to High Fiber Diet Intervention

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female:
• a. The investigators will aim for a 50:50 male:female ratio, at most 40:60. Therefore, given a sample size of N=40, if 24 eligible participants are exceed for one gender, the investigators will proceed with recruitment only for members of the underrepresented gender.
• Between 18 and 35 years of age (expand to 55 if needed)
• BMI between 18.5 ≥ BMI \> 25 kg/m2 (expand to 30 if needed)
• Born in Europe
• Current resident of Luxembourg City or Esch-sur-Alzette (expand to nearby communes if needed)
• Own a smartphone with access to Android or Apple Store applications

You may not qualify if:

• Following a specific diet or subject to dietary restrictions for any reason
• "Vigorous" physical activity level based on the International Physical Activity Questionnaire - Short Form (IPAQ-SF) criteria
• Antibiotics usage within the past 3 months
• Probiotics usage within the past 1 month
• Laxatives usage within the past 1 month
• Other regular medication usage (e.g. ibuprofen, warfarin)
• Current or former smoker
• Gastrointestinal disorder (e.g. ulcerative colitis, Crohn's disease) diagnosis
• History of gastrointestinal surgery (excluding appendectomy)
• Metabolic disorder diagnosis or predisposition (determined by blood test at eligibility screen)
• Prediabetes: fasting glucose 100-125 mg/dL (6.1-7.0 mmol/L) and/or drug treatment of elevated glucose (8)
• Diabetes: fasting glucose ≥126 mg/dL (7.0 mmol/L) and/or drug treatment of elevated glucose and/or previously diagnosed type 1 or type 2 diabetes (8)
• Hypertriglyceridaemia: fasting triglycerides ≥1.7 mmol/L (≥150 mg/dL) and/or drug treatment for elevated triglycerides (9)
• Hypercholesterolaemia: Fasting High-density lipoprotein cholesterol (HDL-C) \< 40 mg/dL (\< 1.0 mmol/L) in men and \< 45 mg/dL (\< 1.2mmol/L) in women and/or drug treatment for reduced HDL-C (9)
• Hypertension: Systolic BP ≥130 and/or diastolic BP ≥80 mm Hg and/or drug treatment of previously diagnosed hypertension (10)

Sponsors & Collaborators

• Luxembourg Institute of Health: lead
• Centre Hospitalier du Luxembourg: collaborator
• Integrated Biobank of Luxembourg: collaborator
• University of Luxembourg: collaborator

Study Sites (2)

Luxembourg Institute of Health

Esch-sur-Alzette, 4354, Luxembourg

Location

Luxembourg Institute of Health

Strassen, 4356, Luxembourg

Location

Related Publications (7)

• Martens EC, Neumann M, Desai MS. Interactions of commensal and pathogenic microorganisms with the intestinal mucosal barrier. Nat Rev Microbiol. 2018 Aug;16(8):457-470. doi: 10.1038/s41579-018-0036-x.

  PMID: 29904082 BACKGROUND

• Desai MS, Seekatz AM, Koropatkin NM, Kamada N, Hickey CA, Wolter M, Pudlo NA, Kitamoto S, Terrapon N, Muller A, Young VB, Henrissat B, Wilmes P, Stappenbeck TS, Nunez G, Martens EC. A Dietary Fiber-Deprived Gut Microbiota Degrades the Colonic Mucus Barrier and Enhances Pathogen Susceptibility. Cell. 2016 Nov 17;167(5):1339-1353.e21. doi: 10.1016/j.cell.2016.10.043.

  PMID: 27863247 BACKGROUND

• Belzer C, de Vos WM. Microbes inside--from diversity to function: the case of Akkermansia. ISME J. 2012 Aug;6(8):1449-58. doi: 10.1038/ismej.2012.6. Epub 2012 Mar 22.

  PMID: 22437156 BACKGROUND

• Weir TL, Manter DK, Sheflin AM, Barnett BA, Heuberger AL, Ryan EP. Stool microbiome and metabolome differences between colorectal cancer patients and healthy adults. PLoS One. 2013 Aug 6;8(8):e70803. doi: 10.1371/journal.pone.0070803. Print 2013.

  PMID: 23940645 BACKGROUND

• Jangi S, Gandhi R, Cox LM, Li N, von Glehn F, Yan R, Patel B, Mazzola MA, Liu S, Glanz BL, Cook S, Tankou S, Stuart F, Melo K, Nejad P, Smith K, Topcuolu BD, Holden J, Kivisakk P, Chitnis T, De Jager PL, Quintana FJ, Gerber GK, Bry L, Weiner HL. Alterations of the human gut microbiome in multiple sclerosis. Nat Commun. 2016 Jun 28;7:12015. doi: 10.1038/ncomms12015.

  PMID: 27352007 BACKGROUND

• Hou JK, Abraham B, El-Serag H. Dietary intake and risk of developing inflammatory bowel disease: a systematic review of the literature. Am J Gastroenterol. 2011 Apr;106(4):563-73. doi: 10.1038/ajg.2011.44.

  PMID: 21468064 BACKGROUND

• 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.

  PMID: 24336217 BACKGROUND

MeSH Terms

Conditions

Inflammatory Bowel Diseases

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Study Officials

• Mahesh S Desai, PhD

  Luxembourg Institute of Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: This study involves recruitment of healthy volunteers to participate in a 2x2 crossover design controlled-diet study.

Study Record Dates

• First Submitted: February 26, 2020
• First Posted: April 20, 2020
• Study Start: February 22, 2021
• Primary Completion: December 5, 2022
• Study Completion: December 5, 2022
• Last Updated: December 8, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will share
• Time Frame: Data will become available to share with other researchers at the time of publication. Accession numbers for sequencing data will be published in the manuscript.
• Access Criteria: All IPD will be pseudonymised. Researchers requesting use of this data should make an inquiry by email to the Principal Investigator explaining the purpose of their proposed work and what types of metadata they are interested in before any data sharing can be approved. In keeping with data minimization policies, we will share only the data that is relevant for the proposed analyses. Furthermore, data may not be shared if the participant has indicated on their consent form that they do not wish their data to be used in follow up studies (in the same or a different field of research).

Locations

LU (2)