Enteric ChAT-Expressing Neurons Mediate the Protective Effect of Lactobacillus plantarum in Inflammatory Bowel Disease.
5 affiliations
- 1College of Food Science and Engineering, Northwest A&F University, Yangling, China.
- 2State Key Laboratory of Eco-Hydraulics in Northwest Arid Region of China, School of Water Resources and Hydro-Electric Engineering, Xi'an University of Technology, Xi'an, China.
- 3Department of Gastroenterology, Shaanxi Provincial People's Hospital, Xi'an, China.
- 4Faculty of Food Science and Engineering, Yunnan Institute of Food Safety, Kunming University of Science and Technology, Kunming, China.
- 5Institute of Molecular and Cell Biology (IMCB), Agency for Science Technology and Research (A*STAR), Singapore.
Abstract
The gut microbiota plays a crucial role in inflammatory bowel diseases (IBD), yet how specific microbial components influence disease progression remains incompletely understood. Our study reveals that decreased abundance of Lactobacillus species correlates with ulcerative colitis severity in patients. Among tested strains, L. plantarum A736, isolated from traditional fermented foods, demonstrated protective effects in ameliorating dextran sulfate sodium (DSS)-induced colitis in a mouse model. Strikingly, multi-omics analysis revealed that L. plantarum A736 uniquely enhances choline acetyltransferase-expressing (ChAT⁺) neurons in the enteric nervous system and elevates acetylcholine (ACh) levels. Further analysis identified that L. plantarum A736 metabolizes tryptophan to produce indole-3-lactic acid (ILA), and supplementation with ILA significantly mimics this strain's anti-inflammatory effects by restoring ChAT⁺ neurons and cholinergic signaling. Crucially, selective ablation of colonic ChAT⁺ neurons abolished the protective effect of both L. plantarum A736 and ILA, establishing their essential role in mediating these effects. These findings demonstrate that microbial metabolites can modulate enteric neuronal circuits to regulate gut immunity. The identified ILA-ChAT⁺ neuron axis represents a novel neuro-immune pathway that could be targeted for IBD treatment.
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BibTeX
@article{xia2026enteric,
title = {{Enteric ChAT-Expressing Neurons Mediate the Protective Effect of Lactobacillus plantarum in Inflammatory Bowel Disease.}},
author = {Bing Xia and Yuwei Sun and Jialin Wang and Yike Liu and Lu Wang and Shiqi Jiang and Gaiyan Bai and Ruijing Zhang and Yu Zhang and Rongwei Kou and Danna Wang and Beita Zhao and Junjie Yi and Yu Fu and Xiaoning Liu and Xuebo Liu},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
year = {2026},
month = oct,
doi = {10.1002/advs.77455},
url = {https://europepmc.org/article/MED/42876090},
note = {CC BY},
}
RIS
TY - JOUR
TI - Enteric ChAT-Expressing Neurons Mediate the Protective Effect of Lactobacillus plantarum in Inflammatory Bowel Disease.
AU - Bing Xia
AU - Yuwei Sun
AU - Jialin Wang
AU - Yike Liu
AU - Lu Wang
AU - Shiqi Jiang
AU - Gaiyan Bai
AU - Ruijing Zhang
AU - Yu Zhang
AU - Rongwei Kou
AU - Danna Wang
AU - Beita Zhao
AU - Junjie Yi
AU - Yu Fu
AU - Xiaoning Liu
AU - Xuebo Liu
PY - 2026
DA - 2026/10/14
JO - Advanced science (Weinheim, Baden-Wurttemberg, Germany)
DO - 10.1002/advs.77455
UR - https://europepmc.org/article/MED/42876090
AB - The gut microbiota plays a crucial role in inflammatory bowel diseases (IBD), yet how specific microbial components influence disease progression remains incompletely understood. Our study reveals that decreased abundance of Lactobacillus species correlates with ulcerative colitis severity in patients. Among tested strains, L. plantarum A736, isolated from traditional fermented foods, demonstrated protective effects in ameliorating dextran sulfate sodium (DSS)-induced colitis in a mouse model. Strikingly, multi-omics analysis revealed that L. plantarum A736 uniquely enhances choline acetyltransferase-expressing (ChAT⁺) neurons in the enteric nervous system and elevates acetylcholine (ACh) levels. Further analysis identified that L. plantarum A736 metabolizes tryptophan to produce indole-3-lactic acid (ILA), and supplementation with ILA significantly mimics this strain's anti-inflammatory effects by restoring ChAT⁺ neurons and cholinergic signaling. Crucially, selective ablation of colonic ChAT⁺ neurons abolished the protective effect of both L. plantarum A736 and ILA, establishing their essential role in mediating these effects. These findings demonstrate that microbial metabolites can modulate enteric neuronal circuits to regulate gut immunity. The identified ILA-ChAT⁺ neuron axis represents a novel neuro-immune pathway that could be targeted for IBD treatment.
SN - 2198-3844
ER -