Metagenomic Characterization of the Intestinal Microbiota in ALS Patients and Association With Clinical Phenotypes

Amyotrophic Lateral Sclerosis

ALS, Amyotrophic Lateral Sclerosis, microbiota, gut microbiota, french gut

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease involving motor neurons in the cerebral cortex, brain stem and spinal cord. Loss of functional motor neurons is responsible for rapid progressive muscle paralysis, generally leading to death from respiratory failure within 3 to 5 years. Data obtained in mouse models of the disease suggest that changes in the intestinal microbiota may be involved in the pathophysiology of the disease. However, to date, there are no solid data on the existence of intestinal dysbiosis in ALS patients and its prognostic influence. The ALS-Gut study will make it possible for the first time to quantitatively and qualitatively characterize the gut microbiota in a large population of French ALS patients, and to identify changes associated with the disease compared with healthy subjects. It will also identify possible associations between observed deviations in microbiota and the ALS phenotype, its management modalities, and its evolutionary profile. This study will thus pave the way for innovative therapeutic strategies aimed at re-establishing a favorable gut microbiota profile, in order to limit the progression of motor impairment. The aim of the ALS-Gut study is to quantitatively and qualitatively characterize the microbiota in a cohort of 300 French ALS patients, and to correlate these results with the clinical features of the disease. The ALS-Gut study will be based on the Le French Gut project carried out by a consortium comprising INRAE, AP-HP, INSERM and Institut Pasteur on 100,000 volunteers, aimed at characterizing the heterogeneity and diversity of the intestinal microbiota of subjects living in France. The ALS-Gut study is a non-human research study, which will use clinical data collected prospectively in 18 French ALS expert centers as part of the routine management of 300 French ALS patients participating in the Le French Gut project.

The ALS-Gut study aims to quantitatively and qualitatively characterize the microbiota in a cohort of 300 French ALS patients, and to correlate these results with the clinical features of the disease. The ALS-Gut study will build on the Le French Gut project conducted by a consortium comprising INRAE, AP-HP, INSERM and Institut Pasteur on 100,000 volunteers, aimed at characterizing the heterogeneity and diversity of the gut microbiota of subjects living in France (https://lefrenchgut.fr). The French Gut is a non-interventional study (protocol appended) involving human subjects. It is prospective, nationwide, with the creation of a biological collection (faeces) linked to the exploitation of data from questionnaires and the Système National des Données de Santé (SNDS). Following volunteer registration via the study's dedicated website, a stool sample will be taken at home for analysis of the fecal microbiota by shotgun metagenomic sequencing. The various components of the microbiota will then be compared with individual data obtained from specific questionnaires, completed on the French Gut website by the volunteer, such as dietary habits or current state of health. The French Gut project will map the healthy gut microbiota in France, and also describe variations in gut microbiota associated with the presence and development of certain diseases, particularly neurodegenerative diseases such as ALS. The ALS-Gut study is a non-human research study, which will use clinical data collected prospectively in 18 French ALS expert centers as part of the routine management of 300 French ALS patients participating in the Le French Gut project. The clinical data collected as part of the ALS-Gut study will be analyzed in conjunction with the metagenomic results obtained by INRAE, based on a stool sample sent to the French Gut consortium by the patient in advance, on a voluntary basis.

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