Gut microbe–derived <i>N</i> -acyl serinol lipids shape host postprandial metabolic homeostasis

S Sumita Dutta (Department of Microbial Sciences in Health, Cleveland Clinic Research) K Kala K. Mahen (Department of Microbial Sciences in Health, Cleveland Clinic Research) W William J. Massey (Department of Inflammation and Immunity, Cleveland Clinic Research) V Venkateshwari Varadharajan (Department of Microbial Sciences in Health, Cleveland Clinic Research) A Amy C. Burrows (Department of Microbial Sciences in Health, Cleveland Clinic Research) A Anthony J. Horak (Department of Microbial Sciences in Health, Cleveland Clinic Research) M Marko Mrdjen (Department of Microbial Sciences in Health, Cleveland Clinic Research) N Nour Mouannes (Department of Microbial Sciences in Health, Cleveland Clinic Research) D Danny Orabi (Center for Microbiome and Human Health, Cleveland Clinic Research) L Lucas J. Osborn (Department of Heart, Blood, and Kidney Research, Cleveland Clinic Research) T Treg Grubb (Department of Cancer Sciences, Cleveland Clinic Research) R Rachel C. Hohe (Department of Microbial Sciences in Health, Cleveland Clinic Research) R Rakhee Banerjee (Department of Microbial Sciences in Health, Cleveland Clinic Research) V Vinayak Uppin (Department of Microbial Sciences in Health, Cleveland Clinic Research) D Dev Laungani (Department of Microbial Sciences in Health, Cleveland Clinic Research) G Grace E. Hamilton (Department of Microbial Sciences in Health, Cleveland Clinic Research) X Xiayan Ye (Department of Microbial Sciences in Health, Cleveland Clinic Research) N Naseer Sangwan (Center for Microbiome and Human Health, Cleveland Clinic Research) M Mohammed Dwidar A Adeline M. Hajjar (Center for Microbiome and Human Health, Cleveland Clinic Research) B Belinda Willard M Michael Martin (Cayman Chemical) E Erik Guetschow (Cayman Chemical) P Patrick Westcott (Cayman Chemical) M Megan R. McMullen (Department of Inflammation and Immunity, Cleveland Clinic Research) L Laura E. Nagy Z Zeneng Wang (Center for Microbiome and Human Health, Cleveland Clinic Research) S Stanley L. Hazen (Center for Microbiome and Human Health, Cleveland Clinic Research) J J. Mark Brown (Department of Microbial Sciences in Health, Cleveland Clinic Research)

Abstract

Although strong evidence links the gut microbiome to metabolic disease, the mechanisms linking microbiota to hormonal and metabolic responses to food are not well understood. After a meal, gut bacteria produce a wide array of small molecule, protein, and lipid metabolites originating from bacterial sources. Attributing physiological function to select gut microbe–derived metabolites is critical to understanding diet–microbe–host interactions, and to developing microbiome-inspired therapies to improve human health. Here, we have investigated the role of a poorly annotated class of gut microbiome-derived lipids called N -acyl amides in postprandial metabolic physiology. Here, we show that both bacterial production and provision of exogenous N -acyl amides reorganize host hormone-driven metabolic transition after a meal. Moreover, N -acyl amides exert broad effects on the meal- and circadian-related reorganization of gene expression, metabolic hormones, and gut microbiome composition. Collectively, these results demonstrate that microbiota-derived N -acyl amides play a physiologic role in postprandial metabolic homeostasis in the host.

Article Details

Volume / Issue Vol. 123, Issue 12
Published March 24, 2026
ISSN 0027-8424
Publisher National Academy of Sciences

Authors (29)

S

Sumita Dutta

Department of Microbial Sciences in Health, Cleveland Clinic Research

K

Kala K. Mahen

Department of Microbial Sciences in Health, Cleveland Clinic Research

W

William J. Massey

Department of Inflammation and Immunity, Cleveland Clinic Research

V

Venkateshwari Varadharajan

Department of Microbial Sciences in Health, Cleveland Clinic Research

A

Amy C. Burrows

Department of Microbial Sciences in Health, Cleveland Clinic Research

A

Anthony J. Horak

Department of Microbial Sciences in Health, Cleveland Clinic Research

M

Marko Mrdjen

Department of Microbial Sciences in Health, Cleveland Clinic Research

N

Nour Mouannes

Department of Microbial Sciences in Health, Cleveland Clinic Research

D

Danny Orabi

Center for Microbiome and Human Health, Cleveland Clinic Research

L

Lucas J. Osborn

Department of Heart, Blood, and Kidney Research, Cleveland Clinic Research

T

Treg Grubb

Department of Cancer Sciences, Cleveland Clinic Research

R

Rachel C. Hohe

Department of Microbial Sciences in Health, Cleveland Clinic Research

R

Rakhee Banerjee

Department of Microbial Sciences in Health, Cleveland Clinic Research

V

Vinayak Uppin

Department of Microbial Sciences in Health, Cleveland Clinic Research

D

Dev Laungani

Department of Microbial Sciences in Health, Cleveland Clinic Research

G

Grace E. Hamilton

Department of Microbial Sciences in Health, Cleveland Clinic Research

X

Xiayan Ye

Department of Microbial Sciences in Health, Cleveland Clinic Research

N

Naseer Sangwan

Center for Microbiome and Human Health, Cleveland Clinic Research

M

Mohammed Dwidar

A

Adeline M. Hajjar

Center for Microbiome and Human Health, Cleveland Clinic Research

B

Belinda Willard

M

Michael Martin

Cayman Chemical

E

Erik Guetschow

Cayman Chemical

P

Patrick Westcott

Cayman Chemical

M

Megan R. McMullen

Department of Inflammation and Immunity, Cleveland Clinic Research

L

Laura E. Nagy

Z

Zeneng Wang

Center for Microbiome and Human Health, Cleveland Clinic Research

S

Stanley L. Hazen

Center for Microbiome and Human Health, Cleveland Clinic Research

J

J. Mark Brown

Department of Microbial Sciences in Health, Cleveland Clinic Research