Circadian misalignment associates with inflammation, gut barrier, and microbiome composition in humans with obesity

Circadian disruption has been linked to metabolic syndrome, but the biological links between circadian phenotypes and metabolic inflammation in humans remain incompletely characterized. We analyzed 87 adults with obesity from a randomized clinical trial to examine whether gut microbiome features and intestinal permeability relate to circadian misalignment and metabolic inflammation. Circadian phenotype was assessed using chronotype and meal timing, metabolic inflammation through a composite score of multiple biological measures, and gut permeability using sugar absorption testing. Late chronotype was associated with greater metabolic syndrome burden, while circadian misalignment was associated with increased gut permeability and inflammation, an association stronger among participants with higher permeability. These patterns co-occurred with lower abundance of short-chain fatty acid-associated bacteria, and intervention-related changes in permeability corresponded with changes in these taxa. These findings link circadian phenotypes with gut barrier and microbial features relevant to metabolic risk in obesity.