Gut microbiota-driven imbalance of the gut-brain-immune homeostatic network in constipation: Pathogenic mechanisms and evolving therapeutic prospects
Abstract
Chronic constipation (CC) is increasingly recognized as a systems-level disorder that cannot be explained by impaired intestinal motility alone. Here, we integrate evidence from clinical cohorts, animal models, and mechanistic studies to examine how gut microbial dysbiosis and altered microbial metabolites perturb epithelial barrier integrity, immune homeostasis, enteric neural activity, and gut-brain signaling. We propose a "gut-brain-immune homeostatic network" in which short-chain fatty acids (SCFAs), tryptophan metabolites, bile acids, and other microbial signals may sustain self-reinforcing interactions linking dysmotility, inflammation, and neurobehavioral disturbances. We further evaluate microbiota-directed interventions, including prebiotics, probiotics, postbiotics, fecal microbiota transplantation, engineered bacteria, and multi-omics-guided personalized strategies. This framework reframes CC as a multisystem homeostatic disorder and provides a mechanistic basis for patient stratification, therapeutic target discovery, and precision interventions for constipation and related gut-brain-immune disorders.
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BibTeX
@article{zhu2026microbiotadriven,
title = {{Gut microbiota-driven imbalance of the gut-brain-immune homeostatic network in constipation: Pathogenic mechanisms and evolving therapeutic prospects}},
author = {Jianing Zhu and Binbin Zeng and Wenxu Zhu and Ying Liu and Xin Li and Yapei Zhang and Zhiheng Xu and Qingqing Xu and Wenjin Wu and Jialu Li and Xiaoyu Shang and Ying Lin and Tianyu Zhou and Feng Lu and Yayun Qian},
journal = {iScience},
year = {2026},
month = oct,
doi = {10.1016/j.isci.2026.117850},
url = {https://www.cell.com/iscience/fulltext/S2589-0042(26)03231-1},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Gut microbiota-driven imbalance of the gut-brain-immune homeostatic network in constipation: Pathogenic mechanisms and evolving therapeutic prospects
AU - Jianing Zhu
AU - Binbin Zeng
AU - Wenxu Zhu
AU - Ying Liu
AU - Xin Li
AU - Yapei Zhang
AU - Zhiheng Xu
AU - Qingqing Xu
AU - Wenjin Wu
AU - Jialu Li
AU - Xiaoyu Shang
AU - Ying Lin
AU - Tianyu Zhou
AU - Feng Lu
AU - Yayun Qian
PY - 2026
DA - 2026/10/09
JO - iScience
DO - 10.1016/j.isci.2026.117850
UR - https://www.cell.com/iscience/fulltext/S2589-0042(26)03231-1
AB - Chronic constipation (CC) is increasingly recognized as a systems-level disorder that cannot be explained by impaired intestinal motility alone. Here, we integrate evidence from clinical cohorts, animal models, and mechanistic studies to examine how gut microbial dysbiosis and altered microbial metabolites perturb epithelial barrier integrity, immune homeostasis, enteric neural activity, and gut-brain signaling. We propose a "gut-brain-immune homeostatic network" in which short-chain fatty acids (SCFAs), tryptophan metabolites, bile acids, and other microbial signals may sustain self-reinforcing interactions linking dysmotility, inflammation, and neurobehavioral disturbances. We further evaluate microbiota-directed interventions, including prebiotics, probiotics, postbiotics, fecal microbiota transplantation, engineered bacteria, and multi-omics-guided personalized strategies. This framework reframes CC as a multisystem homeostatic disorder and provides a mechanistic basis for patient stratification, therapeutic target discovery, and precision interventions for constipation and related gut-brain-immune disorders.
SN - 2589-0042
ER -