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Gut microbial ammonia enhances colonic acetylcholine levels to regulate intestinal motility.

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Τίτλος: Gut microbial ammonia enhances colonic acetylcholine levels to regulate intestinal motility.
Συγγραφείς: Chen H; Human Microbiome and Health Group, Department of Microbiology, Xiangya School of Basic Medical Sciences, Central South University, Changsha, China., Wang Z; Human Microbiome and Health Group, Department of Microbiology, Xiangya School of Basic Medical Sciences, Central South University, Changsha, China., Zhao Y; Human Microbiome and Health Group, Department of Microbiology, Xiangya School of Basic Medical Sciences, Central South University, Changsha, China., Yang W; Human Microbiome and Health Group, Department of Parasitology, Xiangya School of Basic Medical Sciences, Central South University, Changsha, China., Huang J; Human Microbiome and Health Group, Department of Parasitology, Xiangya School of Basic Medical Sciences, Central South University, Changsha, China., Yu Z; Human Microbiome and Health Group, Department of Microbiology, Xiangya School of Basic Medical Sciences, Central South University, Changsha, China. yuzheng@csu.edu.cn.
Πηγή: Nature microbiology [Nat Microbiol] 2026 Apr; Vol. 11 (4), pp. 907-919. Date of Electronic Publication: 2026 Feb 20.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101674869 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2058-5276 (Electronic) Linking ISSN: 20585276 NLM ISO Abbreviation: Nat Microbiol Subsets: MEDLINE
Imprint Name(s): Original Publication: [London] : Nature Publishing Group, [2016]-
Ιατρικοί όροι (MeSH): Acetylcholine*/metabolism , Acetylcholine*/deficiency , Gastrointestinal Motility*/physiology , Ammonia*/metabolism , Colon*/metabolism , Gastrointestinal Microbiome*/physiology, Urease/metabolism ; Constipation/microbiology ; Constipation/physiopathology ; Animals ; Mice ; Humans ; Male ; Disease Models, Animal ; Mice, Inbred C57BL ; Female
Περίληψη: Intestinal motility is a function of the enteric nervous system involving secretion of the excitatory neurotransmitter acetylcholine (ACh). Although gut commensal bacteria are key regulators of intestinal physiology, the molecular mechanisms underlying microbial influence on intestinal peristalsis and constipation remain unclear. Here we report a link between microbial nitrogen metabolism and intestinal motility regulation via ammonia production. We observed compensatory elevation of intestinal ammonia levels and urease activity in mouse models of intestinal dysmotility, induced by ACh deficiency, and in patients with constipation. Ammonia supplementation or intervention in mice with the urease-positive Lysinibacillus fusiformis isolated from patient stool, or engineered urease-expressing bacteria, effectively restored colonic ACh levels. In vitro, ammonia upregulated the expression of voltage-gated calcium channels on enteric neurons, driving Ca2+ influx to potentiate ACh secretion. Our study reveals a microbial compensatory mechanism that responds to fluctuating ACh levels in the intestine and provides microbial targets for intestinal motility disorders.
(© 2026. The Author(s), under exclusive licence to Springer Nature Limited.)
Competing Interests: Competing interests: The authors declare no competing interests.
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Grant Information: 32170071 National Natural Science Foundation of China (National Science Foundation of China); 32300051 National Natural Science Foundation of China (National Science Foundation of China); 2025JJ50101 Natural Science Foundation of Hunan Province (Hunan Provincial Natural Science Foundation); 2023JJ30651 Natural Science Foundation of Hunan Province (Hunan Provincial Natural Science Foundation)
Substance Nomenclature: N9YNS0M02X (Acetylcholine)
7664-41-7 (Ammonia)
EC 3.5.1.5 (Urease)
Entry Date(s): Date Created: 20260220 Date Completed: 20260708 Latest Revision: 20260708
Update Code: 20260708
DOI: 10.1038/s41564-026-02269-8
PMID: 41721075
Βάση Δεδομένων: MEDLINE
Περιγραφή
ISSN:2058-5276
DOI:10.1038/s41564-026-02269-8