A Model for Microbiota-Mediated Regulation and Intervention of Intestinal Motility

Abstract

Intestinal motility is essential for nutrient absorption, waste excretion, and toxin clearance, and its impairment underlies functional constipation, slow-transit constipation, and irritable bowel syndrome. While traditional research has focused on smooth muscle contractility and enteric nervous system (ENS) autonomy, emerging evidence highlights the gut microbiota as a critical regulator. This perspective article synthesizes recent findings into the 'Microbiota-Mediated Regulation and Intervention of Intestinal Motility' model, proposing that dysmotility arises from a vicious cycle of microbiota dysbiosis, impaired motility, and exacerbated dysbiosis. The model integrates four regulatory axes—metabolic, neuronal, immunological, and mechanical—through which the microbiota positively drives motility. Key pathways include the butyrate-5-HT axis, tryptophan-aryl hydrocarbon receptor signaling, microbiota-immune balance, and a novel microbiota-ammonia-acetylcholine metabolic compensation pathway. Under pathological conditions, four self-reinforcing sub-loops (butyrate-hypoxia, Piezo2-Fusobacterium, ENS damage, and brain-gut axis) perpetuate the cycle. The model's novelty lies in explicitly integrating these loops and proposing multi-node combination intervention strategies, including pathogen clearance with probiotic augmentation, combined butyrate and prokinetic therapy, metabolic compensation with neuroprotection, and chronoregulatory approaches. This framework provides a comprehensive basis for understanding and treating intestinal motility disorders.

1. Introduction

Intestinal motility underpins nutrient absorption, waste excretion, and toxin clearance. Its impairment is a core pathological feature of functional constipation, slow-transit constipation, irritable bowel syndrome, and related disorders. Traditional research has emphasized the intrinsic contractile properties of intestinal smooth muscle and the autonomous rhythmicity of the enteric nervous system (ENS). However, mounting evidence indicates that the gut microbiota and its metabolites are indispensable regulators of intestinal motility [1]. The data indicate that microbiota and intestinal motility form a bidirectional, homeostatic regulatory system: hypothalamic neurons can rapidly remodel the gut microbiota [2]; the microbiota participates in motility regulation via mechanosensitive channels such as Piezo2 [3]; and transit time critically shapes microbial composition and metabolism [4].

In this perspective article, we synthesize recent findings into a model—termed the 'Microbiota-Mediated Regulation and Intervention of Intestinal Motility' model. We propose that the core pathological pattern of dysmotility is a vicious cycle of 'microbiota dysbiosis→impaired intestinal motility→exacerbated dysbiosis'. Specifically, gut microbiota positively drives intestinal motility through a four-axis network of metabolic, neuronal, immunological, and mechanical signaling; impaired motility, in turn, exacerbates microbiota imbalance by prolonging transit time, altering mechanical signals, and disrupting the anaerobic microenvironment; microbiota-based interventions can restore metabolic capacity and signaling pathways, break the vicious cycle, and reestablish intestinal motility homeostasis. The novelty of this model lies in explicitly integrating four self-reinforcing pathological sub-loops and proposing multi-node combination strategies, as well as articulating a threshold-based transition from compensation to decompensation.