5611
IRUS Total
Downloads
  Altmetric

A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice

File Description SizeFormat 
105810_2_merged_1477067399.pdfAccepted version1.72 MBAdobe PDFView/Open
Title: A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice
Authors: Plovier, H
Everard, A
Depommier, C
Van Hul, M
Geurts, L
Ottman, N
Chilloux, J
Duparc, T
Lichtenstein, L
Myridakis, A
Delzenne, NM
Klievink, J
Bhattacharjee, A
Van der Ark, KC
Aalvink, S
Martinez, LO
Dumas, ME
Maiter, D
Loumaye, A
Hermans, MP
Thissen, JP
Belzer, C
De Vos, WM
Cani, PD
Item Type: Journal Article
Abstract: Obesity and type 2 diabetes are associated with low-grade inflammation and specific changes in gut micro biota composition 1-7 . We previously demonstrat ed that administration of Akkermansia muciniphila prevents the development of obesity and associated complications 8 . However, its mechanisms of action re main unclear, whilst the sensitivity of A. muciniphila to oxygen and the presence of animal-derived compounds in its growth medium currently limit the development of translational approaches for human medicine 9 . Here we addressed these issues by showing that A. muciniphila retains its efficacy when grown on a synthetic medium compatible wi th human administration. Unexpectedly, we discovered that pasteurization of A. muciniphila enhanced its capacity to reduce fat mass development, insulin resistance and dyslip idemia in mice. These improvements were notably associated with a modulation of the host urinary meta bolomics profile and intestinal energy absorption. We demonstrated that Amuc_1100, a specific prot ein isolated from the outer membrane of A. muciniphila , interacts with Toll-Like Receptor 2, is stable at temperatures used for pasteurization, improves the gut barrier and partly recapitulates the beneficial effects of the bacterium. Finally, we showed that administration of live or pasteurized A. muciniphila grown on the synthetic medium is safe in humansThese findings provide support for the use of different preparations of A. muciniphila as therapeutic options to target human obesity and associated disorders.
Issue Date: 1-Jan-2017
Date of Acceptance: 17-Oct-2016
URI: http://hdl.handle.net/10044/1/42901
DOI: 10.1038/nm.4236
ISSN: 1546-170X
Publisher: Nature Publishing Group
Start Page: 107
End Page: 113
Journal / Book Title: Nature Medicine
Volume: 23
Issue: 1
Copyright Statement: © 2016 Nature America, Inc., part of Springer Nature. All rights reserved.
Sponsor/Funder: Commission of the European Communities
Funder's Grant Number: 305312
Keywords: Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Cell Biology
Medicine, Research & Experimental
Research & Experimental Medicine
GUT MICROBIOTA
INTESTINAL EPITHELIUM
INSULIN-RESISTANCE
ATHEROSCLEROSIS
SAFETY
MUCIN
TOLERANCE
DIET
INFLAMMATION
INTEGRITY
Adipose Tissue
Adult
Animals
Blood Glucose
Blotting, Western
Chromatography, Liquid
Diabetes Mellitus, Type 2
Disease Models, Animal
Dyslipidemias
Female
Humans
Insulin Resistance
Intestinal Mucosa
Intestines
Male
Membrane Proteins
Metabolic Syndrome
Mice, Obese
Middle Aged
Obesity
Toll-Like Receptor 2
Verrucomicrobia
Intestines
Intestinal Mucosa
Adipose Tissue
Animals
Humans
Mice, Obese
Diabetes Mellitus, Type 2
Insulin Resistance
Obesity
Disease Models, Animal
Blood Glucose
Membrane Proteins
Blotting, Western
Chromatography, Liquid
Adult
Middle Aged
Female
Male
Dyslipidemias
Toll-Like Receptor 2
Verrucomicrobia
Metabolic Syndrome
Immunology
11 Medical and Health Sciences
Publication Status: Published
Online Publication Date: 2016-11-28
Appears in Collections:Department of Metabolism, Digestion and Reproduction
Department of Surgery and Cancer
Faculty of Medicine