Akkermansia muciniphila induces gut microbiota remodelling and controls islet autoimmunity in NOD mice
Open accessAbstract
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.
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- Authors
- Hänninen, A., Toivonen, R., Pöysti, S., Belzer, C., Plovier, H., Ouwerkerk, J. P., Emani, R., Cani, P. D., & De Vos, W. M.
- Affiliations
- University of Turku (FI)
- Wageningen University & Research (NL)
- Walloon Excellence in Lifesciences and Biotechnology (BE)
- Laboratory of Microbiology, Wagenigen University, Wageningen, The Netherlands
- Corresponding author
- Hänninen, Arno
- Venue
- Gut
- Publisher
- BMJ
- Published
- 2017-12-21
- Volume
- 67
- Issue
- 8
- Pages
- 1445-1453
- ISSN
- 0017-5749 (ISSN-L)
- 1468-3288
- OpenAlex
- W2778672167
- Cited by
- 359
- References
- 7
- Citations by year
- 2026: 21 · 2025: 36 · 2024: 40 · 2023: 47 · 2022: 60 · 2021: 47 · 2020: 42 · 2019: 48 · 2018: 18
- FWCI
- 12.06
- Type
- journal article
- Language
- en
- Open access
- green
- research.wur.nl
- Locations
- Gut (publishedVersion)
- PubMed (publishedVersion)
- Socio-Environmental Systems Modeling (acceptedVersion)
- Digital Access to Libraries (Université catholique de Louvain (UCL), l'Université de Namur (UNamur) and the Université Saint-Louis (USL-B)) (submittedVersion, other-oa)
- Työväentutkimus Vuosikirja (submittedVersion, other-oa)
- HighWire Press Open Archive (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- Suomen Akatemia
- Netherlands Organization for Scientific Research
- Terveyden Tutkimuksen Toimikunta
- H2020 European Research Council
- Funds Baillet Latour
- Päivikki ja Sakari Sohlbergin Säätiö
- FRFS-WELBIO
- Foundation for Diabetes Research Finland
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- Akkermansia muciniphila, type 1 diabetes, islet autoimmunity, gut microbiota, NOD mice, microbiota transfer, probiotics, mucus production, Reg3γ, Ruminococcus torques, endotoxin, Toll-like receptors, autoantibodies
- MeSH terms
- Gastrointestinal Microbiome, Animals, Diabetes Mellitus, Type 1, Disease Models, Animal, Islets of Langerhans, Mice, Inbred NOD, Interleukin-10, T-Lymphocytes, Regulatory, Toll-Like Receptors, Mice, Forkhead Transcription Factors, Verrucomicrobia
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