The Gut Microbiota Axis in Social Jetlag: A Novel Framework for Metabolic Dysfunction and Chronotherapeutic...

Social jetlag, the misalignment between internal circadian rhythms and socially imposed schedules, is increasingly recognized as a risk factor for metabolic disorders such as obesity, type 2 diabetes (T2D), and cardiovascular disease. Recent evidence implicates the gut microbiota as a key mediator in this relationship, operating through a microbiota-gut-metabolic axis that influences host metabolism, immune function, and circadian regulation. Mechanistic studies reveal that social jetlag disrupts microbial rhythmicity, reduces short-chain fatty acid (SCFA) production, impairs intestinal barrier function, and promotes systemic inflammation, which contribute to insulin resistance and metabolic dysfunction. Clinical and preclinical interventions, including time-restricted feeding (TRF)/time-restricted eating (TRE), probiotics or melatonin supplementation, and fecal microbiota transplantation (FMT), demonstrate the potential to restore microbial and metabolic homeostasis by realigning host and microbial rhythms. This review synthesizes mechanistic insights with emerging human and clinical evidence, highlighting the gut microbiota as a novel target for chronotherapeutic strategies aimed at mitigating the metabolic consequences of circadian disruption. Recognizing and treating circadian-microbiome misalignment may provide a clinically actionable pathway to prevent or reverse chronic metabolic diseases in modern populations.