Gut microbiota and circadian disruption in humans: Is there a rationale for metabolic disorders?

Circadian disruption, arising from behaviors such as shift work and sleep deprivation, is increasingly prevalent and associated with metabolic disorders, including obesity, type 2 diabetes, and cardiovascular disease. The gut microbiome plays a crucial role in metabolic homeostasis by producing metabolites - such as short-chain fatty acids, secondary bile acids, and microbial-associated molecular patterns - that influence nutrient absorption, immune responses, and host metabolism in alignment with circadian rhythms. This review explores how circadian disruptors influence the human gut microbiome, focusing on changes in microbial composition, diversity, and functionality, and their implications for metabolic health. Preclinical studies demonstrate that circadian disruptions alter microbial composition, reduce rhythmicity, and impair functionality, contributing to metabolic disorders. However, human studies often report inconsistent findings, with microbial functionality appearing more sensitive to disruptions than composition. Eating patterns affect both the gut microbiome and circadian alignment; their optimization could realign microbial and host rhythms to promote metabolic homeostasis. Future research should focus on longitudinal and interventional studies using advanced methodologies, such as real-time intestinal gas measurements, to capture dynamic microbial activity in humans. Understanding microbial responses to circadian disruptors could inform therapeutic strategies targeting host-microbe interactions to improve metabolic health.