biostudies-literatureZhang YNational Natural Science Foundation of ChinaNational Natural Science Foundation of China (National Science Foundation of China)93https://www.ebi.ac.uk/biostudies/studies/S-EPMC11442948biostudies-literatureUnknown10(1)Stress can lead to gut dysbiosis in brain-gut axis disordered diseases as irritable bowel syndrome (IBS), yet the mechanisms how stress transfer from the brain to the gut and disrupt gut microbiota remain elusive. Here we describe a stress-responsive brain-to-gut axis which impairs colonocytes' mitochondria to trigger gut dysbiosis. Patients with IBS exhibit significantly increased facultative anaerobes and decreased obligate anaerobes, related to increased serum corticotropin-releasing hormone (CRH) level and defected colonocytes' mitochondria ultrastructure. Mice exposed to acute stress experienced enhanced CRH-CRH receptor type 1 (CRHR1) signaling, which impaired mitochondria and epithelium hypoxia in the colon, subsequently triggered gut dysbiosis. Antagonizing CRHR1 expression to inhiNPJ biofilms and microbiomesStress triggers gut dysbiosis via CRH-CRHR1-mitochondria pathway.PMC114429488247057882170557Li XDuan LZheng HZhang ZZhang JZhang YGuo HLu SZhang CPei FWang KfalseStress triggers gut dysbiosis via CRH-CRHR1-mitochondria pathway.Stress can lead to gut dysbiosis in brain-gut axis disordered diseases as irritable bowel syndrome (IBS), yet the mechanisms how stress transfer from the brain to the gut and disrupt gut microbiota remain elusive. Here we describe a stress-responsive brain-to-gut axis which impairs colonocytes' mitochondria to trigger gut dysbiosis. Patients with IBS exhibit significantly increased facultative anaerobes and decreased obligate anaerobes, related to increased serum corticotropin-releasing hormone (CRH) level and defected colonocytes' mitochondria ultrastructure. Mice exposed to acute stress experienced enhanced CRH-CRH receptor type 1 (CRHR1) signaling, which impaired mitochondria and epithelium hypoxia in the colon, subsequently triggered gut dysbiosis. Antagonizing CRHR1 expression to inhi2024-01-01T00:00:00Z2024 Sep2026-06-06T22:20:45.586Z2025-04-04T23:43:05.247ZS-EPMC114429483934948310.1038/s41522-024-00571-z