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Akkermansia muciniphila induces gut microbiota remodelling and controls islet autoimmunity in NOD mice
  1. Arno Hänninen1,2,
  2. Raine Toivonen1,
  3. Sakari Pöysti1,
  4. Clara Belzer3,
  5. Hubert Plovier4,
  6. Janneke P Ouwerkerk3,
  7. Rohini Emani1,
  8. Patrice D Cani4,
  9. Willem M De Vos3,5
  1. 1 Department of Medical Microbiology and Immunology, University of Turku, Turku, Finland
  2. 2 Turku University Hospital, Hospital District of Southwest Finland, Turku, Finland
  3. 3 Laboratory of Microbiology, Wagenigen University, Wageningen, The Netherlands
  4. 4 Metabolism and Nutrition Research Group, Louvain Drug Research Institute, WELBIO (Walloon Excellence in Life sciences and BIOtechnology), Universite Catholique de Louvain, Brussels, Belgium
  5. 5 RPU Immunobiology, Department of Bacteriology and Immunology, University of Helsinki, Helsinki, Finland
  1. Correspondence to Adj. professor Arno Hänninen, Department of Medical Microbiology and Immunology, University of Turku, Turku 20520, Finland; arno.hanninen{at}utu.fi

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 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.

  • autoimmunity
  • bacterial interactions
  • diabetes mellitus
  • gut immunology
  • probiotics

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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 (024.002.002) (WMDV), Academy of Finland (1272870, 137389, 141140 (WMDV) and 285503 (AH)).

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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