Logo image
Back
2576-P: Temporal Reorganization of the Gut Microbiome and Host Clock following Gastric Bypass Restores Metabolic Homeostasis
Abstract   Peer reviewed

2576-P: Temporal Reorganization of the Gut Microbiome and Host Clock following Gastric Bypass Restores Metabolic Homeostasis

Mohamad Mokadem
Diabetes (New York, N.Y.), Vol.75(Suppl 1), p.2576-P
06/01/2026
DOI: 10.2337/db26-2576-P

View Online

Abstract

Introduction and Objective: The circadian clock and gut microbiome are key regulators of metabolic homeostasis, and disruption of either contributes to obesity and insulin resistance. Roux-en-Y gastric bypass (RYGB) produces rapid metabolic improvements and weight loss, but how it affects gut microbial and circadian interactions remains unclear. This study tested whether RYGB reprograms gut microbiota composition and rhythmicity to influence host metabolism and circadian gene expression. Methods: Diet-induced obese male mice underwent RYGB or sham surgery and were compared with lean controls. Samples were collected across four circadian time points (ZT3, ZT9, ZT15, ZT21). Metabolic phenotyping included fasting glucose, insulin, glucose tolerance, and energy expenditure. Cecal microbiota were profiled by 16S rRNA sequencing, and circadian gene expression (CLOCK, BMAL1, PER1/2, CRY1/2) was measured in liver and suprachiasmatic nucleus. Multivariate analyses (MaAsLin2, PCA, PERMANOVA) evaluated microbial, circadian, and metabolic relationships. Results: RYGB reduced body weight, fasting glucose, and insulin despite higher caloric intake. It altered microbial diversity and restored diurnal stability disrupted by obesity. PCA revealed temporal variations (ZT3, ZT15) between lean and sham mice but not RYGB mice. Coriobacteriaceae UCG-002 and unclassified Lactobacillales correlated positively with fasting insulin, while Lactobacillales correlated negatively with fasting glucose. Hepatic Per1 expression associated positively with Butyricicoccus and negatively with Eggerthellaceae. Microbial α-diversity correlated with dark-cycle feeding and light-cycle energy expenditure. Conclusion: RYGB reprograms gut microbiome composition and its diurnal dynamics, linking microbial oscillations to improved metabolic function and circadian regulation.
 Circadian Rhythms Gastrointestinal Surgery Gene Expression Metabolism Obesity Oscillations BMAL1 protein Body weight loss Cecum Circadian rhythm Cryptochromes Diurnal Energy expenditure Fasting Gastric bypass Glucose Glucose tolerance Gut microbiota Homeostasis Insulin resistance Intestinal microflora Microbiomes Microbiota Period 1 protein rRNA 16S Suprachiasmatic nucleus Temporal variability Weight control

Details

Metrics

1 Record Views
Logo image