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

"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."

Common inclusion criteria :

• Patient with ALS that is possible, probable with the support of complementary examinations, clinically probable or defined according to the revised El Escorial diagnostic criteria (Brooks, et al. 2000).
• Follow-up in one of the 18 French ALS expert centers participating in the study.
• Age ≥18 years
• Social security affiliation or beneficiary
• Informed of the ALS-Gut study and not objecting to the collection of his/her data

Common non-inclusion criteria:

• Other concomitant neurodegenerative pathology
• Persons subject to a protective measure, notably guardianship or trusteeship, or unable to express their consent.

PATIENTS ALREADY INCLUDED IN FRENCH GUT 1. Patient agrees to provide French Gut with his or her participation number.

PATIENTS NOT YET INCLUDED IN FRENCH GUT

Inclusion criteria

specific to patients not included in the French Gut study :

• Patient agreeing to take part in the French Gut project, i.e. registering on his or her own initiative, on the project's dedicated website (https://lefrenchgut.fr/) and completing a detailed questionnaire. Then, on receipt of the stool sampling kit at home, return the stool sample to INRAE.

Specific non-inclusion criteria for patients not included in the French Gut (criteria linked to the French Gut) :

• Person not living in France
• Person who has had a colectomy (declarative) ;
• Person with a digestive stoma (declarative);
• Colonoscopy performed in the 3 months prior to inclusion (declarative).
• Antibiotics taken in the 3 months prior to inclusion (self-reported);

Secondary exclusion criteria specific to patients included in the ALS-Gut study prior to inclusion in French Gut

• No response to the French Gut entry questionnaire
• Failure to send a compliant stool sample
• Person who has not signed a French Gut consent form