Circadian misalignment reshapes gut microbial rhythms to underlie digestive disorders

2026-08-06

Yanling Yang

Zi‐Ran Kang

Jilin Wang

Ya-Qi Wang

Ya-Hui Li

Wei Zhang

Yuan-Hong Xie

Tingting Yan

Shan Wu

Hao-Yan Chen

Jing-Yuan Fang

Shan-Shan Jiang *

Hui-Min Chen *

DOI：10.1038/s41522-026-01109-1

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Abstract

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Daily oscillations generated by the host circadian clock, together with rhythmic processes arising from the gut microbiota, form an integrated temporal framework that shapes digestive physiology. The host circadian clock shapes the gastrointestinal landscape through coordinated regulation of feeding patterns, epithelial renewal, immune surveillance, and bile acid metabolism. In turn, the gut microbiota generates rhythmic metabolites that provide reciprocal feedback to epithelial, metabolic, and immune pathways, further reinforcing circadian organization. Disruption of this bidirectional alignment, whether caused by altered light exposure, irregular eating patterns, genetic variation, or lifestyle-induced circadian misalignment, can fragment microbial oscillations, weaken mucosal resilience, and increase susceptibility to inflammatory, metabolic, and malignant digestive disorders. In this Review, we synthesize emerging insights into the molecular architecture that coordinates host and microbial rhythms and examine how its breakdown contributes to gastrointestinal disease. We also discuss chronobiological interventions, including feeding schedules, pharmacological timing, and microbiota-targeted strategies, that aim to restore temporal alignment. Viewing time as a critical functional dimension of host-microbiota biology provides a conceptual foundation for advancing precision diagnostics and therapeutics in digestive health.

Circadian misalignment reshapes gut microbial rhythms to underlie digestive disorders

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