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

Daphne Moutsoglou; Mohammad Jarrah; Jessica Jaques; Leeann Aguilar; Shailesh K Shahi; Ashutosh K Mangalam; Mohamad Mokadem

doi:10.1152/ajpgi.00440.2025

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

Journal article

Open access

Peer reviewed

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

Daphne Moutsoglou, Mohammad Jarrah, Jessica Jaques, Leeann Aguilar, Shailesh K Shahi, Ashutosh K Mangalam and Mohamad Mokadem

American journal of physiology: Gastrointestinal and liver physiology

06/24/2026

DOI: 10.1152/ajpgi.00440.2025

PMID: 42339741

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Abstract

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, ZT21). Principal component analysis at the ASV 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 and 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.

Metabolism

Circadian Rhythms

Gene Expression

encoding genes

microbiome

metabolic pathways

Details

Title: Subtitle: Roux-en-Y gastric bypass alters microbial circadian rhythms with links to metabolic improvement
Creators: Daphne Moutsoglou - University of Minnesota System
Mohammad Jarrah - University of Iowa
Jessica Jaques - University of Iowa
Leeann Aguilar - University of Iowa
Shailesh K Shahi - University of Iowa
Ashutosh K Mangalam - University of Iowa
Mohamad Mokadem - University of Iowa
Resource Type: Journal article
Publication Details: American journal of physiology: Gastrointestinal and liver physiology
DOI: 10.1152/ajpgi.00440.2025
PMID: 42339741
NLM abbreviation: Am J Physiol Gastrointest Liver Physiol
ISSN: 1522-1547
eISSN: 1522-1547
Publisher: American Physiological Society
Grant note: RG-2407-43720 / National Multiple Sclerosis Society 1I01CX002212 / U.S. Department of Veterans Affairs (VA) I01BX006112 / U.S. Department of Veterans Affairs (VA) BX004774-05 / U.S. Department of Veterans Affairs (VA) HT94252510562 / U.S. Department of Defense (DOD)
Language: English
Electronic publication date: 06/24/2026
Academic Unit: Gastroenterology and Hepatology; Pathology; Iowa Neuroscience Institute; Dental Research; Internal Medicine
Record Identifier: 9985176763502771

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