- Faecalibacterium prausnitzii depletion and reduced microbial L-arginine biosynthesis found in insomnia subtypes, correlated with elevated cortisol.
- Administration of F. prausnitzii or L-arginine in stressed mice restores sleep duration, normalises corticosterone and reverses stress-induced gut dysbiosis.
- L-arginine inhibits POMC gene expression and reduces ACTH-stimulated corticosterone, identifying the POMC-ACTH-cortisol axis as therapeutic target.
Cell Rep Med. 2026 Aug 20:102997. doi: 10.1016/j.xcrm.2026.102997. Online ahead of print.
ABSTRACT
Insomnia is associated with gut microbial dysbiosis, but the specific microbial metabolites mediating gut-brain communication remain elusive. Here, we integrate metagenomic sequencing from 171 individuals (primary insomnia, post-COVID insomnia, and controls) with functional pathway analysis and preclinical validation. We identify Faecalibacterium prausnitzii depletion and reduced L-arginine biosynthesis as consistent features in both insomnia subtypes, accompanied by elevated cortisol levels. Genomic and in vitro analyses confirm that F. prausnitzii is a key microbial contributor to L-arginine production. In a chronic mild stress mouse model, administration of either F. prausnitzii or L-arginine restores sleep duration, normalizes corticosterone levels, and reverses stress-induced gut dysbiosis. Mechanistically, L-arginine suppresses POMC gene expression and dampens adrenocorticotropic hormone (ACTH)-stimulated corticosterone release, implicating the POMC-ACTH-cortisol axis as a key target. These findings uncover a gut-brain axis driven by F. prausnitzii-derived L-arginine that modulates sleep through endocrine signaling, positioning this metabolite as a potential therapeutic avenue for insomnia.
PMID:42624113 | DOI:10.1016/j.xcrm.2026.102997
Share Evidence Blueprint
Save to Google Notes
Search Google Scholar
Save as PDF
⭐ My Revision List
