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

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.

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