Akkermansia muciniphila induces gut microbiota remodelling and controls islet autoimmunity in NOD mice

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1 We use cookies to improve our service and to tailor our content and advertising to you. More info Home / Archive / Volume 67, Issue 8 Article Text Article menu Gut microbiota Original article Akkermansia muciniphila induces gut microbiota remodelling and controls islet autoimmunity in NOD mice Arno Hänninen 1, 2, Raine Toivonen 1, Sakari Pöysti 1, Clara Belzer 3, Hubert Plovier 4, Janneke P Ouwerkerk 3, Rohini Emani 1, Patrice D Cani 4, Willem M De Vos 3, 5 PDF Author affiliations Abstract Objective Intestinal microbiota is implicated in the pathogenesis of autoimmune type 1 diabetes in humans and in non-obese diabetic (NOD) mice, but evidence on its causality and on the role of individual microbiota members is limited. We investigated if different diabetes incidence in two NOD colonies was due to microbiota differences and aimed to identify individual microbiota members with potential significance. Design We profiled intestinal microbiota between two NOD mouse colonies showing high or low diabetes incidence by 16S ribosomal RNA gene sequencing and colonised the high-incidence colony with the microbiota of the low-incidence colony. Based on unaltered incidence, we identified a few taxa which were not effectively transferred and thereafter, transferred experimentally one of these to test its potential significance. Results Although the high-incidence colony adopted most microbial taxa present in the low-incidence colony, diabetes incidence remained unaltered. Among the few taxa which were not transferred, Akkermansia muciniphila was identified. As A. muciniphila abundancy is inversely correlated to the risk of developing type 1 diabetes-related autoantibodies, we transferred A. muciniphila experimentally to the 1/6

2 high-incidence colony. A. muciniphila transfer promoted mucus production and increased expression of antimicrobial peptide Reg3γ, outcompeted Ruminococcus torques from the microbiota, lowered serum endotoxin levels and islet toll-like receptor expression, promoted regulatory immunity and delayed diabetes development. Conclusion Transfer of the whole microbiota may not reduce diabetes incidence despite a major change in gut microbiota, but single symbionts such as A. muciniphila with beneficial metabolic and immune signalling effects may reduce diabetes incidence when administered as a probiotic. Statistics from Altmetric.com Picked up by 1 news outlets Blogged by 1 Tweeted by 44 On 2 Facebook pages 58 readers on Mendeley See more details Linked Articles Request Permissions View Full Text Footnotes Contributors: AH and WMDV designed the work; AH analysed data and wrote the first version of the manuscript; RT, SAP, CB, HP, PDC, JPO and RE performed experiments and/or analysed data; WMDV and PDC reviewed the manuscript and wrote parts of the final version, which all authors approved. Funding: This work was supported by Päivikki and Sakari Sohlberg Foundation (AH), Foundation for Diabetes Research Finland (AH), FRFS-WELBIO (WELBIO-CR-2012S-02R) (PDC), Funds Baillet Latour (PDC), European Commission (250172) (PDC), Horizon 2020 Framework Programme of European Research Council (336452) (PDC), H2020 Excellent Science and H2020 European Research Council (250172) (WMDV), Netherlands Organization for Scientific Research ( ) (WMDV), Academy of Finland ( , , (WMDV) and (AH)). Competing interests: None declared. Provenance and peer review: Not commissioned; externally peer reviewed. Request Permissions 2/6

3 If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways. Request permissions Copyright information: Article author(s) (or their employer(s) unless otherwise stated in the text of the article) All rights reserved. No commercial use is permitted unless otherwise expressly granted. Linked Articles Commentary Does Akkermansia muciniphila play a role in type 1 diabetes? Gilles Mithieux Gut 2018; Published Online First: 10 Feb doi: /gutjnl Read the full text or download the PDF: Buy this article ($37) Subscribe Log in 3/6

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