Altered gut microbiota in Rett syndrome

Area of Science:

• Microbiology
• Neuroscience
• Gastroenterology

Background:

• The human gut microbiota significantly impacts health, with dysbiosis linked to gastrointestinal disorders and inflammation.
• Rett syndrome (RTT), a neurological disorder from MeCP2 gene mutations, often presents with gastrointestinal dysfunction, suggesting a microbiota connection.

Purpose of the Study:

• To investigate the bacterial and fungal gut microbiota in RTT subjects.
• To correlate gut microbiota alterations with gastrointestinal abnormalities and inflammation in RTT.

Main Methods:

• Integrated analysis of clinical, metabolomics, and metagenomics data from RTT patients.
• Assessment of fecal calprotectin and erythrocyte sedimentation rate for inflammation markers.

Main Results:

• RTT subjects exhibit intestinal sub-inflammation, evidenced by elevated fecal calprotectin and ESR.
• Altered bacterial and fungal microbiota with reduced richness, dominated by specific taxa (e.g., Bifidobacterium, Clostridia, Candida).
• Gut microbiota changes are independent of constipation and associated with altered short-chain fatty acid profiles.

Conclusions:

• RTT is associated with bacterial and fungal gut dysbiosis, potentially driven by MeCP2 dysfunction.
• The dysbiotic microbiota may contribute to RTT's gastrointestinal pathophysiology and constipation through altered metabolite production.