Host-Microbiota Interaction and Intestinal Epithelial Functions under Circadian Control: Implications in Colitis and Metabolic Disorders.

ABSTRACT

Commensal microbes are involved in intestinal homeostasis, and the dysregulation of host-microbe interactions may lead to the development of local and systemic disorders. Recent evidence indicated that microbiota dysbiosis plays a key role in the pathogenesis of inflammatory bowel disease and metabolism-related disorders. The circadian clock system originally identified in the brain was later found in the gastrointestinal tract. Although the light-controlled central clock in the brain is responsible for the synchronization of peripheral clocks, the timing of meal consumption serves as another cue for the rhythmic setting of gastrointestinal digestion, absorption, and epithelial renewal and barrier functions. Multiple lines of evidence have indicated that in addition to daylight and food intake, microbiota (as an environmental factor) are involved in the circadian control of gut homeostasis. Recent studies demonstrated that microbial metabolites and innate signaling orchestrate the host circadian rhythm, revealing unforeseen molecular mechanisms underlying the regulatory role of microbiota in intestinal physiology and systemic metabolism. In this review, we discuss the host-microbe interplay that contributes to the regulation of intestinal clock signals and physiological functions and explore how microbiota dysbiosis may cause misalignment of circadian systems leading to the development of chronic inflammatory and metabolic diseases.