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  • Review Article
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Akkermansia muciniphila: paradigm for next-generation beneficial microorganisms

Nature Reviews Gastroenterology & Hepatology volume 19, pages 625–637 (2022)Cite this article

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An Author Correction to this article was published on 23 June 2022

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Abstract

Ever since Akkermansia muciniphila was discovered and characterized two decades ago, numerous studies have shown that the lack or decreased abundance of this commensal bacterium was linked with multiple diseases (such as obesity, diabetes, liver steatosis, inflammation and response to cancer immunotherapies). Although primarily based on simple associations, there are nowadays an increasing number of studies moving from correlations to causality. The causal evidence derived from a variety of animal models performed in different laboratories and recently was also recapitulated in a human proof-of-concept trial. In this Review, we cover the history of the discovery of A. muciniphila and summarize the numerous findings and main mechanisms of action by which this intestinal symbiont improves health. A comparison of this microorganism with other next-generation beneficial microorganisms that are being developed is also made.

Key points

  • A lower abundance of Akkermansia muciniphila has been associated with multiple diseases in both mouse models and in humans.

  • A. muciniphila has proven efficacy to improve obesity, type 2 and type 1 diabetes mellitus, hepatic steatosis, intestinal inflammation and different cancers (colon cancer, response to immune checkpoints) in mice.

  • Numerous mechanisms linking A. muciniphila, specific metabolites or membrane proteins and host cell types or receptors have been identified.

  • Pasteurized A. muciniphila MucT is more efficient than the live bacterium and has proven safety and efficacy in numerous studies in mice and in a proof-of-concept study in humans.

  • A. muciniphila contributes to the maintenance of a healthy gut barrier, thereby regulating immunity, and also limits the onset of inflammation, which is the root cause of numerous diseases.

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Fig. 1: Timeline of major advances related to Akkermansia muciniphila.
Fig. 2: Metabolic effects and major factors involved in Akkermansia muciniphila in the context of metabolic health.
Fig. 3: Major mechanisms associated with the effects of Akkermansia or related molecules in diseases.

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Acknowledgements

P.D.C. is research director and A.E. is research associate at FRS-FNRS (Fonds de la Recherche Scientifique) and are recipients of grants from FNRS (Projet de Recherche PDR-convention: FNRS T.0030.21, CDR-convention: J.0027.22, FRFS-WELBIO: WELBIO-CR-2022A-02, WELBIO-CR-2019C-02R, WELBIO-CR-2019S-03, WELBIO-CR-2019S-03R, EOS: program no. 30770923 and program no. 40007505). W.M.dV. was supported by the SIAM Gravitation Grant [024.002.002] of the Netherlands Organization for Scientific Research.

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Authors and Affiliations

  1. UCLouvain, Université catholique de Louvain, Louvain Drug Research Institute, Metabolism and Nutrition Research Group, Walloon Excellence in Life Sciences and BIOtechnology (WELBIO), Brussels, Belgium

    Patrice D. Cani, Clara Depommier & Amandine Everard

  2. Danone Nutricia Research, Palaiseau, France

    Muriel Derrien

  3. Laboratory of Microbiology, Wageningen University, Wageningen, Netherlands

    Willem M. de Vos

  4. Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland

    Willem M. de Vos

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  5. Willem M. de Vos
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The authors contributed equally to all aspects of the article.

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Correspondence to Patrice D. Cani.

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Competing interests

P.D.C., A.E. and W.M.dV. are inventors on patent applications dealing with the use of Akkermansia muciniphila and its components in the treatment of metabolic disorders. P.D.C. and W.M.dV. are co-founders of A-Mansia biotech. M.D. is an employee at Danone Nutricia Research. P.D.C. is co-founder of Enterosys. W.M.dV. is co-founder of Caelus Health and named inventor on patents on the use of Eubacterium hallii. C.D. declares no competing interests.

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Cani, P.D., Depommier, C., Derrien, M. et al. Akkermansia muciniphila: paradigm for next-generation beneficial microorganisms. Nat Rev Gastroenterol Hepatol 19, 625–637 (2022). https://doi.org/10.1038/s41575-022-00631-9

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