Interleukin-36 cytokines alter the intestinal microbiome and can protect against obesity and metabolic dysfunction

Eirini Giannoudaki; Yasmina E Hernandez-Santana; Kelly Mulfaul; Sarah L Doyle; Emily Hams; Padraic G Fallon; Arimin Mat; Donal O'Shea; Manfred Kopf; Andrew E Hogan; Patrick T Walsh

doi:10.1038/s41467-019-11944-w

Back

Interleukin-36 cytokines alter the intestinal microbiome and can protect against obesity and metabolic dysfunction

Journal article

Open access

Peer reviewed

Interleukin-36 cytokines alter the intestinal microbiome and can protect against obesity and metabolic dysfunction

Eirini Giannoudaki, Yasmina E Hernandez-Santana, Kelly Mulfaul, Sarah L Doyle, Emily Hams, Padraic G Fallon, Arimin Mat, Donal O'Shea, Manfred Kopf, Andrew E Hogan, …

Nature communications, Vol.10(1), pp.4003-14

09/05/2019

DOI: 10.1038/s41467-019-11944-w

PMCID: PMC6728358

PMID: 31488830

Files and links (1)

url

https://doi.org/10.1038/s41467-019-11944-wView

Published (Version of record) Open Access

Abstract

Members of the interleukin-1 (IL-1) family are important mediators of obesity and metabolic disease and have been described to often play opposing roles. Here we report that the interleukin-36 (IL-36) subfamily can play a protective role against the development of disease. Elevated IL-36 cytokine expression is found in the serum of obese patients and negatively correlates with blood glucose levels among those presenting with type 2 diabetes. Mice lacking IL-36Ra, an IL-36 family signalling antagonist, develop less diet-induced weight gain, hyperglycemia and insulin resistance. These protective effects correlate with increased abundance of the metabolically protective bacteria Akkermansia muciniphila in the intestinal microbiome. IL-36 cytokines promote its outgrowth as well as increased colonic mucus secretion. These findings identify a protective role for IL-36 cytokines in obesity and metabolic disease, adding to the current understanding of the role the broader IL-1 family plays in regulating disease pathogenesis.

Akkermansia

Animals

Colon - immunology

Colon - microbiology

Colon - pathology

Cytokines - metabolism

Diabetes Mellitus, Type 2

Gastrointestinal Microbiome - immunology

Gastrointestinal Microbiome - physiology

Gene Expression

Glucose Tolerance Test

Host Microbial Interactions - immunology

Host Microbial Interactions - physiology

Humans

Inflammation Mediators - metabolism

Insulin Resistance

Interleukin-1 - genetics

Interleukin-1 - metabolism

Male

Metabolic Diseases - metabolism

Mice

Mice, Inbred C57BL

Mice, Knockout

Mucin-2 - metabolism

Obesity - immunology

Obesity - metabolism

Receptors, Interleukin-1 - genetics

Receptors, Interleukin-1 - metabolism

Transcriptome

Verrucomicrobia

Details

Title: Subtitle: Interleukin-36 cytokines alter the intestinal microbiome and can protect against obesity and metabolic dysfunction
Creators: Eirini Giannoudaki - Trinity College Dublin
Yasmina E Hernandez-Santana - Trinity College Dublin
Kelly Mulfaul - Trinity College Dublin
Sarah L Doyle - Trinity College Dublin
Emily Hams - Trinity College Dublin
Padraic G Fallon - Children's Health Ireland at Crumlin
Arimin Mat - St. Vincent's University Hospital
Donal O'Shea - St. Vincent's University Hospital
Manfred Kopf - ETH Zurich
Andrew E Hogan - National Children’s Research Centre
Patrick T Walsh - National Children’s Research Centre
Resource Type: Journal article
Publication Details: Nature communications, Vol.10(1), pp.4003-14
DOI: 10.1038/s41467-019-11944-w
PMID: 31488830
PMCID: PMC6728358
NLM abbreviation: Nat Commun
ISSN: 2041-1723
eISSN: 2041-1723
Language: English
Date published: 09/05/2019
Academic Unit: Iowa Neuroscience Institute; Neuroscience and Pharmacology
Record Identifier: 9984772267002771

Metrics

7 Record Views

60 Times Cited - Web of Science

See more details