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Do branched chain amino acids counteract protein energy wasting through gut microbiota changes in hemodialysis patients?

English title Do branched chain amino acids counteract protein energy wasting through gut microbiota changes in hemodialysis patients?
Applicant Genton Graf Laurence
Number 163144
Funding scheme Project funding (Div. I-III)
Research institution Endocrinologie, Diabétologie et Nutrition Département de Médecine Interne Hôpitaux Universitaires de Genève
Institution of higher education University of Geneva - GE
Main discipline Clinical Nutritional Research
Start/End 01.06.2016 - 31.12.2019
Approved amount 311'568.00
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Keywords (11)

Appetite; Neuropeptides; Microbiota; Gut associated lymphoid tissue; Hemodialysis; Muscle mass; Nutritional support; Endocannabinoids; Gut barrier; Branched chain amino acids; Wasting

Lay Summary (French)

Lead
Des études récentes montrent l’implication de la flore bactérienne intestinale dans l’obésité et la perte de poids. Par contre on ignore l’impact de la dénutrition et de la renutrition sur la flore et la fonction intestinale chez l’homme. Cette étude vise à déterminer l’effet de la dénutrition et de la renutrition, sur la flore et la fonction intestinale chez des patients dénutris hémodialysés chroniques.
Lay summary

Contenu et objectifs du travail de recherche

Une dénutrition peut survenir lors de maladies chroniques (insuffisance cardiaque, insuffisance rénale, cancer). Elle se manifeste principalement par une perte de masse musculaire et est associée à une augmentation du risque d’hospitalisation et à une diminution de la qualité de vie et de la survie.

Une supplémentation orale en acides aminés branchés, composants naturels de notre alimentation, est connue pour améliorer l’état nutritionnel en stimulant la formation de muscle. Or, une partie des acides aminés branchés consommés oralement ne se retrouve pas dans le sang et suggère que les acides aminés branchés sont utilisés par l’intestin et les bactéries intestinales.

Cette étude vise à montrer que 1) les patients hémodialysés dénutris ont des altérations de la fonction intestinale et de la flore bactérienne et que 2) chez les patients hémodialysés dénutris, une prise orale d’acides aminés branchés améliore l’état nutritionnel en améliorant la fonction de l’intestin et en modifiant la flore bactérienne intestinale. Si cette hypothèse se vérifie, elle ouvrira de nouvelles portes pour le traitement et la prévention de la dénutrition.

 

Contexte scientifique du projet

Ce projet relève de la clinique. Les résultats de cette étude vont améliorer nos connaissances sur les mécanismes de la dénutrition et potentiellement ouvrir de nouvelles possibilités de traitement et de prévention de la dénutrition chez l’homme.

 

 

Direct link to Lay Summary Last update: 26.05.2016

Responsible applicant and co-applicants

Employees

Name Institute

Collaboration

Group / person Country
Types of collaboration
Drug Research Institute Metabolism and Nutrition Research, Louvain (Prof. P. Cani, Dr. G. Muccioli) Belgium (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Nephrology, HUG (C. Stoermann) Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
Centre de recherche en nutrition humaine, Clermont-Ferrant (Prof. Noël Cano) France (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Nephrology, CHUV (PD Dr. D. Teta) Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
Infectious Disease and Genomic Research Lab, HUG (Dr. V. Lazarevic, N. Gaia) Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Nutrition 2019: 18. Dreiländertagung der AKE, DGEM und GESKES Individual talk Wie altert das Mikrobiom mit mir 17.05.2019 Bregenz, Austria Genton Graf Laurence;
Symposium Nutrition-microbiote Individual talk Technical aspects of gut microbiota analysis (Prof. J. Schrenzel) 06.02.2019 Geneva, Switzerland Schrenzel Jacques;
Congrès de la Société Suisse de Néphrologie Individual talk Gut microbiota as a new player in CKD 05.12.2018 Interlaken, Switzerland Genton Graf Laurence;
Congrès suisse de microbiologie Individual talk Nutrition and metagenomics 30.08.2018 Lausanne, Switzerland Genton Graf Laurence;
Congrès de la GESKES/SGAIM 2018 Individual talk Bedeutung des Mikrobioms für die Mangelernährung 31.05.2018 Basel, Switzerland Genton Graf Laurence;
Nutrition 2017: 16. Dreiländertagung der AKE, DGEM und GESKES Individual talk Mikrobiom und Mangelernährung 01.07.2017 Zurich, Switzerland Genton Graf Laurence;


Self-organised

Title Date Place
Symposium Nutrition-microbiote 08.12.2019 Geneva, Switzerland
Symposium Nutrition-microbiota 07.02.2019 Geneva, Switzerland
Symposium Nutrition-microbiote 09.02.2017 Geneva, Switzerland

Communication with the public

Communication Title Media Place Year
Media relations: print media, online media 3. Microbiote : vers de nouveaux espoirs thérapeutiques Pulsations Western Switzerland 2018
New media (web, blogs, podcasts, news feeds etc.) Microbiote YouTube International 2018
Media relations: print media, online media Les secrets du microbiote intestinal Planète Santé Western Switzerland 2017
Media relations: radio, television L'intestin, le tube du siècle Radio Suisse Romande 1ère Western Switzerland 2017
Media relations: print media, online media Se soigner par l'estomac Horizons Italian-speaking Switzerland Rhaeto-Romanic Switzerland Western Switzerland German-speaking Switzerland 2017

Associated projects

Number Title Start Funding scheme
186239 Swiss Centenarian Study (SWISS100): Vulnerability and Resilience at Age 100 01.01.2020 Sinergia

Abstract

AIMS AND HYPOTHESIS: This multicenter study aims at studying the impact of protein energy wasting (PEW) and of refeeding through branched chain amino acids (BCAA) supplements, on gut barrier including gut microbiota, in hemodialysis (HD) patients. The hypotheses are as following:1) HD patients with PEW have altered composition and function of gut microbiota, increased permeability of epithelial gut barrier, increased systemic inflammation but decreased fecal IgA, and a dysbalance of plasma appetite mediators in favor of anorexigenic mediators, compared to HD patients without PEW, non dialyzed patients with chronic kidney disease (CKD) and well-nourished non obese subjects. 2) In HD patients, BCAA supplementation changes gut microbiota, decreases epithelial gut permeability, decreases systemic inflammation and increases fecal IgA and ameliorates plasma balance of appetite mediators in favor of orexigenic mediators. These changes at the gut barrier level are associated with an improvement of nutritional state and eventually of physical function, quality of life, and infection rate. STUDY DESIGNThis multicenter study encompasses two parts, a cross-sectional and a longitudinal study:1) Cross-sectional study: It is performed to differentiate the respective impact of uremia and PEW on gut barrier and gut microbiota. It will compare gut barrier of HD patients with PEW, with gut barrier of age-matched HD well-nourished patients, non dialyzed patients with CKD, and healthy non obese volunteers (10 in each group). This study part is essential for interpretation of the changes occurring in the longitudinal study. 2) Longitudinal double blind randomized crossover study: HD patients with PEW (36 patients), receive, in a randomized double-blind order, either BCAA or an isocaloric isonitrogenous placebo for 4 months each, with a wash-out period of 1 month. The 4-month-duration of each treatment relies on the study of Cano et al. 12. It showed that the implementation of a nutritional support improved nutritional parameters, as plasma albumin, pre-albumin and energy intakes, with a plateau occurring at 4 months. The duration of the washout is based on the study of Dethlefsen et al., who showed that, 4 weeks are necessary to recover most of the taxonomic composition of gut microbiota after an oral antibiotic treatment 100. PRIMARY AND SECONDARY END-POINTS Primary outcome: - gut microbiota composition and function: 16-S high throughput sequencing and shotgun metagenome sequencing.Secondary outcome: - Epithelial gut barrier: fasting levels of plasma GLP-2 and LPS by spectrophotometry. Gut permeability cannot be studied by techniques involving urinary sampling because most HD patients are anuric, and thus requires the use of surrogate markers.- GALT and systemic inflammation: fecal IgA, fasting levels of plasma CRP, IL-10, IL-6, TNF-a by ELISA.- Appetite: fasting levels of plasma cholecystokinin, leptin, peptide YY, glucagon-like peptide-1, neuropeptide Y, ghrelin by ELISA, endocannabinoids by HPLC-MS, visual analogue scale of appetite rating, calorie intakes by 3-day food diary.- Nutritional state: fasting levels of plasma albumin measured by bromocresol green, body composition by dual-energy x-ray absorptiometry, resting energy expenditure by indirect calorimetry.- Clinical end-points: physical activity by 7-day pedometry, handgrip strength, quality of life by SF-36, infection rate and antibiotic use.
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