Abstrakt
The gut microbiome is part of the bidirectional communicational microbiome-gut-brain axis. The communication on this axis is mediated through the autonomic and enteric nervous systems, nervus vagus signaling, immune and enteroendocrine system, the hypothalamus-pituitary-adrenal axis, and various metabolic pathways.
Through this communication axis, the gut microbiota can affect physiological processes such as the quality and duration of sleep. The gut microbiota composition also changes with circadian rhythms.
Gut microbiota is further involved in the regulation of the gut and blood-brain barrier permeability. Microbial dysbiosis is associated with a low-systemic inflammatory state that could support the pathogenesis of narcolepsy.
Narcolepsy type 1 (NT1) is considered an autoimmune disease in which the role of the gut microbiome is being debated. We hypothesize that patients suffering from NT1 may have a microbial dysbiosis or a specific microbial signature that could play a role in the pathogenesis of this disease or in the development of its common comorbidities such as obesity, metabolic syndrome, and depression.
To test this hypothesis, we determined the fecal bacterial composition of patients with type 1 narcolepsy (n=92) and healthy controls (n=51) using next-generation sequencing. The gut microbiota also represents an important antigenic source.
These microbial antigens can structurally mimic some host neuropeptides and neurohormones and thus trigger the production of autoantibodies that cross-react with these compounds. The levels and affinities of such antibodies are associated with a higher prevalence of psychological and metabolic disorders.
We determined the levels of autoantibodies directed to assorted neuropeptides involved in the regulation of sleep and food intake, which could contribute to NT1 pathogenesis. Understanding the role of gut microbiota in NT1 development could bring new therapeutic and preventive approaches targeting this disease.