Inulin-type Fructans-rich Vegetables, Obesity, Gut Microbiota (Food4Gut)

Impact of a Diet Rich in Inulin-type Fructans Combined With Inulin Supplementation on Gut Microbiota Composition and Metabolic Parameters in Obese Patients

The purpose of the study was to evaluate the effect of a diet based on ITF-rich vegetables in combination with purified ITF supplementation on weight management, metabolic alteration and gut microbiota composition. Obese patients were treated for 3 months and several parameters were measured before and after the study period.

Study Overview

• Status: Completed
• Conditions: Obesity
• Intervention / Treatment: Dietary supplement: Placebo; Dietary supplement: Inulin

• Study Type: Interventional
• Enrollment (Actual): 106
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Body mass index > 30 kg/m²
• Caucasian
• Presence of at least one of the following comorbidity : prediabetes, diabetes, dyslipidemia, hypertension, steatosis.

Exclusion Criteria:

• Psychiatric problems or use of antipsychotic
• Consumption of antibiotics, pro/prebiotics, fibre dietary supplement, or any molecules that modifies the intestinal transit (<6 weeks)
• Pregnancy in progress or planified within 6 months
• Specific dietary practise (vegetarian, vegan,...)
• Specific dietary treatment (<6 weeks) (e.g. high protein diet)
• Type 1 diabetes
• Excessive alcohol consumption (>3 glasses/day)
• Inconclusive acceptability test (regarding the protocol of the intervention and the vegetables used in the protocol)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo; 16 g maltodextrin/day + recipes based on vegetables poor in inulin-type fructans	Dietary supplement: Placebo; Patient receive maltodextrin as dietary supplement (16g/d) in combination with dietary advice to restrict caloric intake and to enhance the consumption of vegetables poor in inulin
EXPERIMENTAL: Inulin; 16 g inulin/day + recipes based on vegetables rich in inulin-type fructans	Dietary supplement: Inulin; Patient receive inulin as dietary supplement (16g/d) in combination with dietary advice to restrict caloric intake and to enhance the consumption of inulin-rich vegetables

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gut microbiota composition	Relative abundance (percent) of bacterial taxa will be assessed by 16S rRNA gene sequencing	Month 0 - Month 3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anthropometry	height (cm)	Month 0 - Month 3
Anthropometry	weight (kg)	Month 0 - Month 3
Anthropometry	hip circumference and waist circumference (cm)	Month 0 - Month 3
Anthropometry	Body mass index (BMI, kg/m2)	Month 0 - Month 3
Anthropometry	Body composition by bioimpedance analysis (fat mass, fat free mass, kg)	Month 0 - Month 3
Anthropometry	Body composition by CT scan analysis (fat and muscle areas, cm2)	Month 0 - Month 3
Blood pressure	systolic and diastolic blood pressures (mm Hg)	Month 0 - Month 3
Glucose homeostasis	glycemia (mg/dl) (fasted, after an oral glucose tolerance test)	Month 0 - Month 3
Glucose homeostasis	insulinemia (mU/l) (fasted, after an oral glucose tolerance test)	Month 0 - Month 3
Glucose homeostasis	C-peptide (pM)	Month 0 - Month 3
Glucose homeostasis	glycated hemoglobin HbA1c (percent)	Month 0 - Month 3
Glucose homeostasis	dipeptidyl-peptidase IV activity in the plasma (UI/l)	Month 0 - Month 3
Lipid homeostasis	HLD-Cholesterol, triglycerides, total cholesterol, free fatty acids in the plasma (mg/dl)	Month 0 - Month 3
Hepatic fibrosis and/or steatosis	hepatic enzymes in the plasma (AST, ALT, gamma-glutamyl transpeptidase, U/l)	Month 0 - Month 3
Hepatic fibrosis and/or steatosis	Elasticity by Fibroscan (kPa)	Month 0 - Month 3
Hepatic fibrosis and/or steatosis	controlled attenuation parameter (CAP) by Fibroscan (dB/m)	Month 0 - Month 3
Eating behavior	Questionnaire for Eating Disorders Diagnosis (Q-EDD). The Q-EDD is a 50-items questionnaire based on Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV allowing the psychologist to diagnose eating disorders (anorexia nervosa, bulimia, binge eating), there is no quantitative result.	Month 0 - Month 3
Eating behavior	Dutch Eating Behaviour Questionnaire (DEBQ).The DEBQ is a 33-items questionnaire assessing 3 distinct behaviour: emotional eating (13 items), external eating (10 items) and restrained eating (10 items). Each item is rated on a 5-point scale. A high score is observed when individual tended to eat more when submitted to emotional and external stimuli (for emotional and external eating subscales) or when he displayed elevated cognitive control on its eating behaviour (for the restrained eating subscale).	Month 0 - Month 3
Mood and emotional competence	Positive and Negative Affect Schedule (PANAS, two subscale - positive and negative - from 10 to 50, higher score associated with higher positive and negative emotion respectively)	Month 0 - Month 3
Mood and emotional competence	Scale of Positive and Negative Experience (SPANE, two subscale - positive and negative - from 6 to 30, higher score associated with higher positive and negative emotion respectively)	Month 0 - Month 3
Mood and emotional competence	Profile of Emotional Competence (PEC, from 0 to 5, higher score associated with better emotional competence).	Month 0 - Month 3
Cognition	computer-based tests of the flexibility, the working memory and the inhibition of participants. The measurements will be the time to complete the task on the computer as well as the number of errors.	Month 0 - Month 3
Dietary intake	one-week recall questionnaire to evaluate the dietary intake (macronutrients, caloric intake)	Month 0 - Month 3
Biomarkers of systemic inflammation	Cytokines levels (Il-1β; IL-8; IL-12p70; IL-17a; MCP1; TNFα; IFNγ) by multiplex immunoassay (all in pg/ml)	Month 0 - Month 3
Gut peptides	Gut peptide (GLP-1, GIP, ghrelin, PP, leptin) multiplex immunoassay (all in pg/ml)	Month 0 - Month 3
Metabolomics	metabolomic analysis of biological samples (urine, blood and/or stool)	Month 0 - Month 3
Physical activity	IPAQ questionnaire (The IPAQ long form asks details about the specific types of activities undertaken within the four main domains (leisure time PA, domestic and gardening (yard) activities, work-related PA and transport-related PA). Computation of the total scores for the long form requires summation of the duration (in minutes) and frequency (days) for all the types of activities in all domains. Results allowed us to classify different levels of PA proposed by the questionnaire (total, low-moderate or high-intensity physical activities)	Month 0 - Month 3

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fecal microbial-derived metabolites	Long and short chain fatty acid and bile acid profiles (ng/mg feces or percent) considered as exploratory analyses not initially scheduled in the study but performed in the context of the FiberTAG project. Before inclusion of the study, all participants provided written informed consent stipulating that any research outside the context performed in the future could only be conducted after approval by an ethics committee. We obtained agreement from the ethical committee of Saint-Luc for those exploratory analyses	Month 0 - Month 3
Biomarkers of gut integrity and inflammation	Fecal zonulin (ng/mg feces) considered as exploratory analyses not initially scheduled in the study but performed in the context of the FiberTAG project. Before inclusion of the study, all participants provided written informed consent stipulating that any research outside the context performed in the future could only be conducted after approval by an ethics committee. We obtained agreement from the ethical committee of Saint-Luc for those exploratory analyses	Month 0 - Month 3
Biomarkers of gut integrity and inflammation	fecal albumin (ng/mg feces) considered as exploratory analyses not initially scheduled in the study but performed in the context of the FiberTAG project. Before inclusion of the study, all participants provided written informed consent stipulating that any research outside the context performed in the future could only be conducted after approval by an ethics committee. We obtained agreement from the ethical committee of Saint-Luc for those exploratory analyses	Month 0 - Month 3
Biomarkers of gut integrity and inflammation	fecal calprotectin (ng/mg feces) considered as exploratory analyses not initially scheduled in the study but performed in the context of the FiberTAG project. Before inclusion of the study, all participants provided written informed consent stipulating that any research outside the context performed in the future could only be conducted after approval by an ethics committee. We obtained agreement from the ethical committee of Saint-Luc for those exploratory analyses	Month 0 - Month 3

Collaborators and Investigators

• Sponsor: Cliniques universitaires Saint-Luc- Université Catholique de Louvain

Publications and helpful links

General Publications

• Hiel S, Gianfrancesco MA, Rodriguez J, Portheault D, Leyrolle Q, Bindels LB, Gomes da Silveira Cauduro C, Mulders MDGH, Zamariola G, Azzi AS, Kalala G, Pachikian BD, Amadieu C, Neyrinck AM, Loumaye A, Cani PD, Lanthier N, Trefois P, Klein O, Luminet O, Bindelle J, Paquot N, Cnop M, Thissen JP, Delzenne NM. Link between gut microbiota and health outcomes in inulin -treated obese patients: Lessons from the Food4Gut multicenter randomized placebo-controlled trial. Clin Nutr. 2020 Dec;39(12):3618-3628. doi: 10.1016/j.clnu.2020.04.005. Epub 2020 Apr 13.
• Leyrolle Q, Cserjesi R, Mulders MDGH, Zamariola G, Hiel S, Gianfrancesco MA, Rodriguez J, Portheault D, Amadieu C, Leclercq S, Bindels LB, Neyrinck AM, Cani PD, Karkkainen O, Hanhineva K, Lanthier N, Trefois P, Paquot N, Cnop M, Thissen JP, Klein O, Luminet O, Delzenne NM. Specific gut microbial, biological, and psychiatric profiling related to binge eating disorders: A cross-sectional study in obese patients. Clin Nutr. 2021 Apr;40(4):2035-2044. doi: 10.1016/j.clnu.2020.09.025. Epub 2020 Sep 28.
• Rodriguez J, Neyrinck AM, Van Kerckhoven M, Gianfrancesco MA, Renguet E, Bertrand L, Cani PD, Lanthier N, Cnop M, Paquot N, Thissen JP, Bindels LB, Delzenne NM. Physical activity enhances the improvement of body mass index and metabolism by inulin: a multicenter randomized placebo-controlled trial performed in obese individuals. BMC Med. 2022 Mar 30;20(1):110. doi: 10.1186/s12916-022-02299-z.
• Leyrolle Q, Cserjesi R, Demeure R, Neyrinck AM, Amadieu C, Rodriguez J, Karkkainen O, Hanhineva K, Paquot N, Cnop M, Cani PD, Thissen JP, Bindels LB, Klein O, Luminet O, Delzenne NM. Microbiota and Metabolite Profiling as Markers of Mood Disorders: A Cross-Sectional Study in Obese Patients. Nutrients. 2021 Dec 29;14(1):147. doi: 10.3390/nu14010147.
• Nachit M, Lanthier N, Rodriguez J, Neyrinck AM, Cani PD, Bindels LB, Hiel S, Pachikian BD, Trefois P, Thissen JP, Delzenne NM. A dynamic association between myosteatosis and liver stiffness: Results from a prospective interventional study in obese patients. JHEP Rep. 2021 Jun 15;3(4):100323. doi: 10.1016/j.jhepr.2021.100323. eCollection 2021 Aug.
• Neyrinck AM, Rodriguez J, Zhang Z, Seethaler B, Sanchez CR, Roumain M, Hiel S, Bindels LB, Cani PD, Paquot N, Cnop M, Nazare JA, Laville M, Muccioli GG, Bischoff SC, Walter J, Thissen JP, Delzenne NM. Prebiotic dietary fibre intervention improves fecal markers related to inflammation in obese patients: results from the Food4Gut randomized placebo-controlled trial. Eur J Nutr. 2021 Sep;60(6):3159-3170. doi: 10.1007/s00394-021-02484-5. Epub 2021 Feb 5.
• Leyrolle Q, Cserjesi R, D G H Mulders M, Zamariola G, Hiel S, Gianfrancesco MA, Portheault D, Amadieu C, Bindels LB, Leclercq S, Rodriguez J, Neyrinck AM, Cani PD, Lanthier N, Trefois P, Bindelle J, Paquot N, Cnop M, Thissen JP, Klein O, Luminet O, Delzenne NM. Prebiotic effect on mood in obese patients is determined by the initial gut microbiota composition: A randomized, controlled trial. Brain Behav Immun. 2021 May;94:289-298. doi: 10.1016/j.bbi.2021.01.014. Epub 2021 Jan 28.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 1, 2016
• Primary Completion (ACTUAL): May 1, 2018
• Study Completion (ACTUAL): May 1, 2018

Study Registration Dates

• First Submitted: February 21, 2019
• First Submitted That Met QC Criteria: February 21, 2019
• First Posted (ACTUAL): February 22, 2019

Study Record Updates

• Last Update Posted (ACTUAL): December 22, 2020
• Last Update Submitted That Met QC Criteria: December 18, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity
• Other Study ID Numbers: B403201422056

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