Bacterial Translocation and Gut Microbiota in Type 1 Narcolepsy Patients Versus a Control Population (NARCOBIOTE)

Bacterial Translocation and Gut Microbiota in Type 1 Narcolepsy Patients

Narcolepsy type 1 (NT1) is a rare disease characterized by severe drowsiness, cataplexy, hypnagogic hallucinations, sleep paralysis, poor night sleep, and often obesity. NT1 is caused by irreversible loss of orexin (ORX)/hypocretin neurons in the lateral hypothalamus with decreased ORX levels in the cerebrospinal fluid (CSF). Although the underlying process leading to this destruction remains unclear; an autoimmune origin is suspected.

The study authors recently compared the bacterial communities of the fecal microbiota of NT1 patients and control subjects. Initial results demonstrated a difference in overall bacterial community structure in NT1 compared to controls, as assessed by beta diversity, even after adjusting for body mass index (BMI). The Shannon biodiversity index was also correlated with the duration of NT1 disease. However, no association was found between the structure of the microbial community and the clinical characteristics of NT1 patients.

In 2022, a second study from the SOMNOBANK cohort on a larger population confirmed these results, showing dysbiosis between NT1 patients and the control population. The altered intestinal microbial diversity supports the important role of the environment in the development and pathogenesis of NT1. Other studies have established a link between dysbiosis, intestinal permeability and inflammation in other neuroimmune pathologies. Currently, no study has focused on these phenomena of bacterial translocation, intestinal permeability and immune activation linked to the microbiota in type 1 narcolepsy patients.

The study hypothesis is that NT1 patients with dysbiosis in their intestinal microbiota also present a bacterial translocation with an intestinal origin, leading to a systemic inflammatory syndrome favoring an autoimmune damage destroying hypocretin neurons in the hypothalamus. The study authors suspect that microbial elements (DNA) involved in the autoimmune process could be detected in the CSF. This bacterial translocation could vary over time depending on: i) the progression of the disease and its management; ii) changing dysbiosis and: iii) the increase in intestinal permeability and inflammation.

Study Overview

• Status: Recruiting
• Conditions: Narcolepsy Type 1; Bacterial Translocation
• Intervention / Treatment: Other: Blood sample; Other: Stool sample; Other: CSF sample

• Study Type: Observational
• Enrollment (Estimated): 120

Contacts and Locations

• Study Contact: Name: Catherine Dunyach-Remy; Phone Number: 0466683202; Email: catherine.remy@chu-nimes.fr

Study Locations

• France
  • Montpellier, France
    • Recruiting
    • Centre Hospitalier Universitaire De Montpellier
    • Contact: Yves DAUVILLIERS; Email: y-dauvilliers@chu-montpellier.fr
    • Principal Investigator: Yves DAUVILLIERS
    • Sub-Investigator: Lucie BARATEAU
  • Gard
    • Nîmes, Gard, France, 30029
      • Not yet recruiting
      • Nîmes University Hospital
      • Sub-Investigator: Jean-Philippe Lavigne
      • Contact: Anissa MEGZARI; Phone Number: +33 4 66 68 42 36; Email: drc@chu-nimes.fr
      • Principal Investigator: Catherine DUNYACH-REMY
      • Sub-Investigator: Béatrix ABRIL

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Adults or children (≥10 years) with type 1 narcolepsy managed at the Montpellier and Nîmes teaching hospitals. This population will be matched on sex, age (± 2 years) and BMI class (BMI < 25: normal; 25 ≤ BMI ≤ 30: overweight; BMI > 30: obese) with a population of control subjects without central hypersomnolence, consulting the participating services mainly for another sleep disorder.

Description

Inclusion Criteria:

• Patient diagnosed with narcolepsy type 1 (NT1).
• Patient not treated for narcolepsy during initial evaluation of NT1 patients.
• Patient eligible for treatment for longitudinal monitoring of NT1 patients.
• Patient speaking and understanding French.
• The patient must have given their free and informed consent and signed the consent form or consent has been provided from the holder(s) of parental authority or the legal guardian and the child.
• The patient must be a member or beneficiary of a health insurance plan

Inclusion criteria for control subjects:

• Absence of diagnosis of sleep disorder responsible for hypersomnolence with an Epworth sleepiness scale score greater than 10/24.

Exclusion Criteria:

• Subject having presented an infectious pathology requiring antibiotic treatment in the previous 3 months.
• Subject with a dysimmune pathology.
• Subject having had treatment with an immunomodulatory molecule or chemotherapy within 60 days before inclusion in the research or whose indication is planned for the duration of the research.
• Subject with a chronic digestive pathology or having undergone bariatric surgery in the previous year.
• Subject on laxative.
• Subject living in a medical institution.
• Subject under legal protection, guardianship or curatorship.
• Subject and/or their legal representative (if a minor patient) unable to express consent
• Taking antibiotics during the inclusion period, or laxative or any other treatment having a significant impact on the microbiota

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with untreated NT1	Other: Blood sample; Sample taken to test plasma permeability markers; Other: Stool sample; Sample taken to test microbial diversity and composition; Other: CSF sample; Sample taken to test orexin level
Matched controls; Controls matched on sex, age (+/- 2 years) and BMI class (BMI < 25: normal; 25 ≤ BMI ≤ 30: overweight; BMI > 30: obesity)	Other: Blood sample; Sample taken to test plasma permeability markers; Other: Stool sample; Sample taken to test microbial diversity and composition

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma bacterial translocation profiles between groups	Circulating plasma r16s DNA (copies/μL)	Day 0

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma bacterial translocation profiles in NT1 patients	Circulating plasma r16s DNA (copies/μL)	Month 12
Taxonomic characteristics of DNA in the CSF of NT1 patients according to narcolepsy severity	Metagenomic sequencing of all genomes present, compared with international databases, presented as number of reads per species (bacterial, fungal and viral)	Day 0
Taxonomic characteristics of plasma bacterial DNA in patients with high bacterial translocation	Metabarcoding of 16srDNA of bacterial DNA present in plasma in NT1 patients with 16S rDNA >25 copies/μL, presented as relative abundance of bacterial phyla and genera (%)	Day 0
Taxonomic characteristics of plasma bacterial DNA in patients with high bacterial translocation	Metabarcoding of 16srDNA of bacterial DNA present in plasma in NT1 patients with 16S rDNA >25 copies/μL, presented as relative abundance of bacterial phyla and genera (%)	Month 12
Beta diversity of the intestinal microbiota between groups	measured by metabarcoding	Day 0
Beta diversity of the intestinal microbiota in NT1 patients	measured by metabarcoding	Month 12
Alpha diversity of the intestinal microbiota between groups	measured by metabarcoding	Day 0
Alpha diversity of the intestinal microbiota in NT1 patients	measured by metabarcoding	Month 12
Composition of the intestinal microbiota between groups	Relative abundance of bacterial phyla and genera (%) measured by metabarcoding	Day 0
Composition of the intestinal microbiota between groups	Relative abundance of bacterial phyla and genera (%) measured by metabarcoding	Month 12
Plasma Intestinal Fatty Acid Binding Protein (i-FABP) profile between groups	Measured by ELISA (pg/mL)	Day 0
Plasma Intestinal Fatty Acid Binding Protein (i-FABP) profile in NT1 patients	Measured by ELISA (pg/mL)	Month 12
Plasma LPS-binding Protein (LBP) profile between groups	Measured by ELISA (μg/mL	Day 0
Plasma LPS-binding Protein (LBP) profile in NT1 patients	Measured by ELISA (μg/mL	Month 12
Plasma Soluble CD14 profile between groups	Measured by ELISA (μg/mL	Day 0
Plasma Soluble CD14 profile in NT1 patients	Measured by ELISA (μg/mL	Month 12
Age of onset of symptoms in NT1 patients	Years	Day 0
Duration of disease progression in NT1 patients	Years	Day 0
Severity of sleep-related symptoms in NT1 patients	Epworth scale	Day 0
Severity of narcolepsy symptoms in NT1 patients	Narcolepsy Severity Scale	Day 0
Description of comorbidities in NT1 patients	List	Day 0
Sleep onset latency in NT1 patients	Minutes	Day 0
Number of rapid eye movement sleep episodes in NT1 patients	Number	Day 0
Orexin levels in CSF in NT1 patients	Measured by Radio-immuno-assay (pg/ml)	Day 0

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Nīmes
• Investigators: Principal Investigator: Catherine Dunyach-Remy, CHU de Nîmes

Study record dates

Study Major Dates

• Study Start (Actual): March 10, 2025
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: February 27, 2024
• First Submitted That Met QC Criteria: February 27, 2024
• First Posted (Actual): March 5, 2024

Study Record Updates

• Last Update Posted (Actual): November 17, 2025
• Last Update Submitted That Met QC Criteria: November 14, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Disorders of Excessive Somnolence; Narcolepsy; Investigative Techniques; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Blood Specimen Collection
• Other Study ID Numbers: AOI2022/2023/CDR-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No