Roux-en-Y gastric bypass alters microbial circadian rhythms with links to metabolic improvement

The circadian clock and gut microbiome are integral regulators of metabolic homeostasis, with disruptions in either system contributing to obesity pathogenesis. Roux-en-Y gastric bypass (RYGB) effectively treats severe obesity, yet the mechanisms underlying its benefits remain incompletely characterized. We investigated the impact of RYGB on cecal gut microbial composition and function using 16S rRNA sequencing in relation to host circadian gene expression and metabolic parameters in diet-induced obese mice. Diet-induced obese mice underwent RYGB or sham surgery and were compared with lean controls across multiple circadian Zeitgeber time (ZT) points (ZT3, ZT9, ZT15, and ZT21). Principal component analysis at the amplicon sequence variant level revealed significant differences in all ZT points (ZT3, ZT9, ZT15, and ZT21) in the lean and sham-operated mice; however, only a significant difference between ZT9 and ZT21 was observed in RYGB mice. Microbial gene counts and microbial pathways were also different between RYGB and sham-operated mice, with several correlating with hepatic Clock and Bmal1 gene expression. Notably, specific taxa showed differential associations with glucose homeostasis, independent of surgical intervention. These findings demonstrate that RYGB alters the gut microbiome and host circadian rhythms, suggesting an association between microbial remodeling, circadian gene expression, and metabolic improvement following bariatric surgery.NEW & NOTEWORTHY We find that Roux-en-Y gastric bypass alters circadian patterns, including taxonomy, microbial metabolic gene counts, and microbial metabolic pathways that align with circadian gene expression, Clock, Liver Period1, and Bmal1. These findings in Roux-en-Y gastric bypass mice differ from those in sham-operated mice (also on a high-fat diet), which may contribute to the metabolic benefits of the surgery.