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Akkermansia muciniphila: biology, microbial ecology, host interactions and therapeutic potential

Nature Reviews Microbiology volume 23, pages 162–177 (2025)Cite this article

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Abstract

Akkermansia muciniphila is a gut bacterium that colonizes the gut mucosa, has a role in maintaining gut health and shows promise for potential therapeutic applications. The discovery of A. muciniphila as an important member of our gut microbiome, occupying an extraordinary niche in the human gut, has led to new hypotheses on gut health, beneficial microorganisms and host–microbiota interactions. This microorganism has established a unique position in human microbiome research, similar to its role in the gut ecosystem. Its unique traits in using mucin sugars and mechanisms of action that can modify host health have made A. muciniphila a subject of enormous attention from multiple research fields. A. muciniphila is becoming a model organism studied for its ability to modulate human health and gut microbiome structure, leading to commercial products, a genetic model and possible probiotic formulations. This Review provides an overview of A. muciniphila and Akkermansia genus phylogeny, ecophysiology and diversity. Furthermore, the Review discusses perspectives on ecology, strategies for harnessing beneficial effects of A. muciniphila for human mucosal metabolic and gut health, and its potential as a biomarker for diagnostics and prognostics.

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Fig. 1: Biological features of A. muciniphila.
Fig. 2: Enzymatic arsenal of A. muciniphila for the degradation of mucin glycans and human milk oligosaccharides.
Fig. 3: A. muciniphila and its interaction with the host.
Fig. 4: Ecological interactions between A. muciniphila and other members of the human gut microbiota.
Fig. 5: Current and future potential applications of A. muciniphila.

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References

  1. Matijašić, M. et al. Gut microbiota beyond bacteria—mycobiome, virome, archaeome, and eukaryotic parasites in IBD. Int. J. Mol. Sci. 21, 2668 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  2. Sender, R., Fuchs, S. & Milo, R. Revised estimates for the number of human and bacteria cells in the body. PLoS Biol. 14, e1002533 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  3. Davenport, E. R. et al. The human microbiome in evolution. BMC Biol. 15, 127 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  4. Goodrich, J. K. et al. Human genetics shape the gut microbiome. Cell 159, 789–799 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Lange, K., Buerger, M., Stallmach, A. & Bruns, T. Effects of antibiotics on gut microbiota. Dig. Dis. 34, 260–268 (2016).

    Article  PubMed  Google Scholar 

  6. Bokulich, N. A. et al. Antibiotics, birth mode, and diet shape microbiome maturation during early life. Sci. Transl. Med. 8, 343ra82 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  7. Perler, B. K., Friedman, E. S. & Wu, G. D. The role of the gut microbiota in the relationship between diet and human health. Annu. Rev. Physiol. 85, 449–468 (2023).

    Article  CAS  PubMed  Google Scholar 

  8. Adak, A. & Khan, M. R. An insight into gut microbiota and its functionalities. Cell. Mol. Life Sci. 76, 473–493 (2019).

    Article  CAS  PubMed  Google Scholar 

  9. Jandhyala, S. M. et al. Role of the normal gut microbiota. World J. Gastroenterol. 21, 8836–8847 (2015).

    Article  Google Scholar 

  10. Haneishi, Y. et al. Inflammatory bowel diseases and gut microbiota. Int. J. Mol. Sci. 24, 3817 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Christovich, A. & Luo, X. M. Gut microbiota, leaky gut, and autoimmune diseases. Front. Immunol. 13, 946248 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Wang, P. X., Deng, X. R., Zhang, C. H. & Yuan, H. J. Gut microbiota and metabolic syndrome. Chin. Med. J. 133, 808–816 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Bagheri, Z., Moeinzadeh, L. & Razmkhah, M. Roles of microbiota in cancer: from tumor development to treatment. J. Oncol. 2022, 3845104 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  14. Akagawa, S. & Kaneko, K. Gut microbiota and allergic diseases in children. Allergol. Int. 71, 301–309 (2022).

    Article  CAS  PubMed  Google Scholar 

  15. Sorboni, S. G., Moghaddam, H. S., Jafarzadeh-Esfehani, R. & Soleimanpour, S. A comprehensive review on the role of the gut microbiome in human neurological disorders. Clin. Microbiol. Rev. 35, e0033820 (2022).

    Article  PubMed  Google Scholar 

  16. Maciel-Fiuza, M. F. et al. Role of gut microbiota in infectious and inflammatory diseases. Front. Microbiol. 14, 1098386 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  17. Derrien, M., Vaughan, E. E., Plugge, C. M. & de Vos, W. M. Akkermansia muciniphila gen. nov., sp. nov., a human intestinal mucin-degrading bacterium. Int. J. Syst. Evol. Microbiol. 54, 1469–1476 (2004). This paper describes the discovery and basic characterization of A. muciniphila.

    Article  CAS  PubMed  Google Scholar 

  18. van Passel, M. W. J. et al. The genome of Akkermansia muciniphila, a dedicated intestinal mucin degrader, and its use in exploring intestinal metagenomes. PLoS ONE 6, e16876 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  19. Derrien, M. et al. Mucin–bacterial interactions in the human oral cavity and digestive tract. Gut Microbes 1, 254–268 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  20. Belzer, C. et al. Microbial metabolic networks at the mucus layer lead to diet-independent butyrate and vitamin B12 production by intestinal symbionts. mBio 8, 1–14 (2017). This in vitro study is a proof-of-principle study demonstrating that A. muciniphila cross-feeds other bacteria within the microbiome.

    Article  Google Scholar 

  21. Ottman, N., Geerlings, S. Y., Aalvink, S., de Vos, W. M. & Belzer, C. Action and function of Akkermansia muciniphila in microbiome ecology, health and disease. Best. Pract. Res. Clin. Gastroenterol. 31, 637–642 (2017).

    Article  PubMed  Google Scholar 

  22. Everard, A. et al. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proc. Natl Acad. Sci. USA 110, 9066–9071 (2013). This mouse study provides insights into the role of A. muciniphila in the context of obesity and type 2 diabetes.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Chelakkot, C. et al. Akkermansia muciniphila-derived extracellular vesicles influence gut permeability through the regulation of tight junctions. Exp. Mol. Med. 50, e450 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Van Der Lugt, B. et al. Akkermansia muciniphila ameliorates the age-related decline in colonic mucus thickness and attenuates immune activation in accelerated aging Ercc1–/Δ7 mice. Immun. Ageing 16, 1–17 (2019).

    Google Scholar 

  25. Cani, P. D., Depommier, C., Derrien, M., Everard, A. & de Vos, W. M. Akkermansia muciniphila: paradigm for next-generation beneficial microorganisms. Nat. Rev. Gastroenterol. Hepatol. 19, 625–637 (2022).

    Article  PubMed  Google Scholar 

  26. Ley, R. E. et al. Evolution of mammals and their gut microbes. Science 320, 1647–1651 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Sommer, F. et al. The gut microbiota modulates energy metabolism in the hibernating brown bear Ursus arctos. Cell Rep. 14, 1655–1661 (2016).

    Article  CAS  PubMed  Google Scholar 

  28. Carey, H. V., Walters, W. A. & Knight, R. Seasonal restructuring of the ground squirrel gut microbiota over the annual hibernation cycle. Am. J. Physiol. Regul. Integr. Comp. Physiol. 304, R33–R42 (2013).

    Article  CAS  PubMed  Google Scholar 

  29. Sonoyama, K. et al. Response of gut microbiota to fasting and hibernation in Syrian hamsters. Appl. Env. Microbiol. 75, 6451–6456 (2009).

    Article  CAS  Google Scholar 

  30. Costello, E. K., Gordon, J. I., Secor, S. M. & Knight, R. Postprandial remodeling of the gut microbiota in Burmese pythons. ISME J. 4, 1375–1385 (2010).

    Article  CAS  PubMed  Google Scholar 

  31. Ouwerkerk, J. P. et al. Adaptation of Akkermansia muciniphila to the oxic–anoxic interface of the mucus layer. Appl. Env. Microbiol. 82, 6983–6993 (2016). This work shows the unique adaptation of A. muciniphila to the oxygen gradient of the mucus layer.

    Article  CAS  Google Scholar 

  32. Belzer, C. & de Vos, W. M. Microbes inside—from diversity to function: the case of Akkermansia. ISME J. 6, 1449–1458 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Green, T. J., Smullen, R. & Barnes, A. C. Dietary soybean protein concentrate-induced intestinal disorder in marine farmed Atlantic salmon, Salmo salar is associated with alterations in gut microbiota. Vet. Microbiol. 166, 286–292 (2013).

    Article  CAS  PubMed  Google Scholar 

  34. Derrien, M., Collado, M. C., Ben-Amor, K., Salminen, S. & De Vos, W. M. The mucin degrader Akkermansia muciniphila is an abundant resident of the human intestinal tract. Appl. Env. Microbiol. 74, 1646–1648 (2008).

    Article  CAS  Google Scholar 

  35. Karcher, N. et al. Genomic diversity and ecology of human-associated Akkermansia species in the gut microbiome revealed by extensive metagenomic assembly. Genome Biol. 22, 1–24 (2021). This research describes a large-scale population genomics dataset of the genus Akkermansia and reveals a large phylogenetic and functional diversity of this genus.

    Article  Google Scholar 

  36. Collado, M. C., Derrien, M., Isolauri, E., De Vos, W. M. & Salminen, S. Intestinal integrity and Akkermansia muciniphila, a mucin-degrading member of the intestinal microbiota present in infants, adults, and the elderly. Appl. Env. Microbiol. 73, 7767–7770 (2007).

    Article  CAS  Google Scholar 

  37. Guo, X. et al. Different subtype strains of Akkermansia muciniphila abundantly colonize in southern China. J. Appl. Microbiol. 120, 452–459 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Geerlings, S. Y., Kostopoulos, I., de Vos, W. M. & Belzer, C. Akkermansia muciniphila in the human gastrointestinal tract: when, where, and how? Microorganisms 6, 75 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Momozawa, Y., Deffontaine, V., Louis, E. & Medrano, J. F. Characterization of bacteria in biopsies of colon and stools by high throughput sequencing of the V2 region of bacterial 16S rRNA gene in human. PLoS ONE 6, e16952 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Nayfach, S., Shi, Z. J., Seshadri, R., Pollard, K. S. & Kyrpides, N. C. New insights from uncultivated genomes of the global human gut microbiome. Nature 568, 505–510 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Palmas, V. et al. Gut microbiota markers and dietary habits associated with extreme longevity in healthy Sardinian centenarians. Nutrients 14, 2436 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Biagi, E. et al. Through ageing, and beyond: gut microbiota and inflammatory status in seniors and centenarians. PLoS ONE 5, e10667 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  43. Biagi, E. et al. Gut microbiota and extreme longevity. Curr. Biol. 26, 1480–1485 (2016).

    Article  CAS  PubMed  Google Scholar 

  44. Wu, L. et al. Gut microbiota as an antioxidant system in centenarians associated with high antioxidant activities of gut-resident Lactobacillus. NPJ Biofilms Microbiomes 8, 102 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Kim, B.-S. et al. Comparison of the gut microbiota of centenarians in longevity villages of South Korea with those of other age groups. J. Microbiol. Biotechnol. 29, 429–440 (2019).

    Article  PubMed  Google Scholar 

  46. Wang, F. et al. Gut microbiota community and its assembly associated with age and diet in Chinese centenarians. J. Microbiol. Biotechnol. 25, 1195–1204 (2015).

    Article  CAS  PubMed  Google Scholar 

  47. Cătoi, A. F. et al. Gut microbiota and aging—a focus on centenarians. Biochim. Biophys. Acta, Mol. Cell Res. 1866, 165765 (2020).

    Article  Google Scholar 

  48. Lv, Q.-B. et al. A thousand metagenome-assembled genomes of Akkermansia reveal phylogroups and geographical and functional variations in the human gut. Front. Cell Infect. Microbiol. 12, 957439 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Daniel, N., Gewirtz, A. T. & Chassaing, B. Akkermansia muciniphila counteracts the deleterious effects of dietary emulsifiers on microbiota and host metabolism. Gut 72, 906–917 (2023).

    Article  CAS  PubMed  Google Scholar 

  50. Guo, X. et al. Genome sequencing of 39 Akkermansia muciniphila isolates reveals its population structure, genomic and functional diversity, and global distribution in mammalian gut microbiotas. BMC Genomics 18, 800 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  51. González, D., Morales-Olavarria, M., Vidal-Veuthey, B. & Cárdenas, J. P. Insights into early evolutionary adaptations of the Akkermansia genus to the vertebrate gut. Front. Microbiol. 14, 1238580 (2023). This paper reports the genomic potential of Akkermansia spp. in relation to environmental conditions that have led to traits important for colonization of the gut.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Kumar, R. et al. Identification and characterization of a novel species of genus Akkermansia with metabolic health effects in a diet-induced obesity mouse model. Cells 11, 2084 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Truong, D. T., Tett, A., Pasolli, E., Huttenhower, C. & Segata, N. Microbial strain-level population structure and genetic diversity from metagenomes. Genome Res. 27, 626–638 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Geerlings, S. Y. et al. Genomic convergence between Akkermansia muciniphila in different mammalian hosts. BMC Microbiol. 21, 298 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Luna, E. et al. Utilization efficiency of human milk oligosaccharides by human-associated Akkermansia is strain dependent. Appl. Env. Microbiol. 88, e0148721 (2022).

    Article  Google Scholar 

  56. Ouwerkerk, J. P., Aalvink, S., Belzer, C. & de Vos, W. M. Akkermansia glycaniphila sp. nov., an anaerobic mucin-degrading bacterium isolated from reticulated python faeces. Int. J. Syst. Evol. Microbiol. 66, 4614–4620 (2016).

    Article  CAS  PubMed  Google Scholar 

  57. Ndongo, S., Armstrong, N., Raoult, D. & Fournier, P. E. Reclassification of eight Akkermansia muciniphila strains and description of Akkermansia massiliensis sp. nov. and Candidatus Akkermansia timonensis, isolated from human feces. Sci. Rep. 12, 21747 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Liu, Q. et al. Akkermansia muciniphila exerts strain-specific effects on DSS-induced ulcerative colitis in mice. Front. Cell Infect. Microbiol. 11, 698914 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Kirmiz, N. et al. Comparative genomics guides elucidation of Vitamin B12 biosynthesis in novel human-associated Akkermansia strains. Appl. Env. Microbiol. 86, e02117–e02119 (2020).

    Article  CAS  Google Scholar 

  60. Zhai, R. et al. Strain-specific anti-inflammatory properties of two Akkermansia muciniphila strains on chronic colitis in mice. Front. Cell Infect. Microbiol. 9, 239 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Ottman, N. et al. Characterization of outer membrane proteome of Akkermansia muciniphila reveals sets of novel proteins exposed to the human intestine. Front. Microbiol. 7, 1157 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  62. Ligthart, K., Belzer, C., de Vos, W. M. & Tytgat, H. L. P. Bridging bacteria and the gut: functional aspects of type IV pili. Trends Microbiol. 28, 340–348 (2020).

    Article  CAS  PubMed  Google Scholar 

  63. Ottman, N. et al. Pili-like proteins of Akkermansia muciniphila modulate host immune responses and gut barrier function. PLoS ONE 12, 1–18 (2017). This study discovers the pili-like protein Amuc_1100, and describes its effect on host immune response and gut barrier function.

    Article  Google Scholar 

  64. Xiang, R., Wang, J., Xu, W., Zhang, M. & Wang, M. Amuc_1102 from Akkermansia muciniphila adopts an immunoglobulin-like fold related to archaeal type IV pilus. Biochem. Biophys. Res. Commun. 547, 59–64 (2021).

    Article  CAS  PubMed  Google Scholar 

  65. Reunanen, J. et al. Akkermansia muciniphila adheres to enterocytes and strengthens the integrity of the epithelial cell layer. Appl. Env. Microbiol. 81, 3655–3662 (2015). This paper shows that A. muciniphila adheres to human colonic cell lines and increases cell layer integrity.

    Article  CAS  Google Scholar 

  66. Elzinga, J. et al. Binding of Akkermansia muciniphila to mucin is O-glycan specific. Nat. Commun. 15, 4582 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Kostopoulos, I. et al. A continuous battle for host-derived glycans between a mucus specialist and a glycan generalist in vitro and in vivo. Front. Microbiol. 12, 1–14 (2021).

    Article  Google Scholar 

  68. Garcia-Vello, P. et al. Peptidoglycan from Akkermansia muciniphila MucT: chemical structure and immunostimulatory properties of muropeptides. Glycobiology 32, 712–719 (2022).

    Article  CAS  PubMed  Google Scholar 

  69. van der Ark, K. C. H. et al. Model-driven design of a minimal medium for Akkermansia muciniphila confirms mucus adaptation. Microb. Biotechnol. 11, 476–485 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  70. Ottman, N. et al. Genome-scale model and omics analysis of metabolic capacities of Akkermansia muciniphila reveal a preferential mucin-degrading lifestyle. Appl. Env. Microbiol. 83, e01014–e01017 (2017).

    Article  CAS  Google Scholar 

  71. Parada Venegas, D. et al. Short chain fatty acids (SCFAs)-mediated gut epithelial and immune regulation and its relevance for inflammatory bowel diseases. Front. Immunol. 10, 277 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  72. Hernández, M. A. G., Canfora, E. E., Jocken, J. W. E. & Blaak, E. E. The short-chain fatty acid acetate in body weight control and insulin sensitivity. Nutrients 11, 1943 (2019).

    Article  PubMed  Google Scholar 

  73. Bridgeman, S. C. et al. Butyrate generated by gut microbiota and its therapeutic role in metabolic syndrome. Pharmacol. Res. 160, 105174 (2020).

    Article  CAS  PubMed  Google Scholar 

  74. Hosseini, E., Grootaert, C., Verstraete, W. & Van de Wiele, T. Propionate as a health-promoting microbial metabolite in the human gut. Nutr. Rev. 69, 245–258 (2011).

    Article  PubMed  Google Scholar 

  75. De Vadder, F. et al. Microbiota-generated metabolites promote metabolic benefits via gut–brain neural circuits. Cell 156, 84–96 (2014).

    Article  PubMed  Google Scholar 

  76. Corfield, A. P., Wagner, S. A., Clamp, J. R., Kriaris, M. S. & Hoskins, L. C. Mucin degradation in the human colon: production of sialidase, sialate O-acetylesterase, N-acetylneuraminate lyase, arylesterase, and glycosulfatase activities by strains of fecal bacteria. Infect. Immun. 60, 3971–3978 (1992).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Tailford, L. E., Crost, E. H., Kavanaugh, D. & Juge, N. Mucin glycan foraging in the human gut microbiome. Front. Genet. 6, 81 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  78. Bakshani, C. R. et al. Carbohydrate-active enzymes from Akkermansia muciniphila. Preprint at bioRxiv https://doi.org/10.1101/2024.03.27.586211 (2024).

  79. Huang, K. et al. Biochemical characterisation of the neuraminidase pool of the human gut symbiont Akkermansia muciniphila. Carbohydr. Res. 415, 60–65 (2015).

    Article  CAS  PubMed  Google Scholar 

  80. Shuoker, B. et al. Sialidases and fucosidases of Akkermansia muciniphila are crucial for growth on mucin and nutrient sharing with mucus-associated gut bacteria. Nat. Commun. 14, 1833 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Kostopoulos, I. et al. Akkermansia muciniphila uses human milk oligosaccharides to thrive in the early life conditions in vitro. Sci. Rep. 10, 14330 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Davey, L. E. et al. A genetic system for Akkermansia muciniphila reveals a role for mucin foraging in gut colonization and host sterol biosynthesis gene expression. Nat. Microbiol. 8, 1450–1467 (2023). This study reports a genetic system for A. muciniphila, applies transposon mutagenesis to A. muciniphila and gives insight into the importance of mucin-degrading enzymes for gut colonization.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Lee, J. Y. et al. Nutrient-specific proteomic analysis of the mucin degrading bacterium Akkermansia muciniphila. Proteomics 22, 2100125 (2022).

    Article  CAS  Google Scholar 

  84. Kosciow, K. & Deppenmeier, U. Characterization of three novel β-galactosidases from Akkermansia muciniphila involved in mucin degradation. Int. J. Biol. Macromol. 149, 331–340 (2020).

    Article  CAS  PubMed  Google Scholar 

  85. Crouch, L. I. et al. Prominent members of the human gut microbiota express endo-acting O-glycanases to initiate mucin breakdown. Nat. Commun. 11, 4017 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Kosciow, K. & Deppenmeier, U. Characterization of a phospholipid-regulated β-galactosidase from Akkermansia muciniphila involved in mucin degradation. Microbiologyopen 8, 1–11 (2019).

    Article  Google Scholar 

  87. Berkhout, M. D., Plugge, C. M. & Belzer, C. How microbial glycosyl hydrolase activity in the gut mucosa initiates microbial cross-feeding. Glycobiology 32, 182–200 (2022).

    Article  CAS  PubMed  Google Scholar 

  88. Ouwerkerk, J. P. et al. Comparative genomics and physiology of Akkermansia muciniphila isolates from human intestine reveal specialized mucosal adaptation. Microorganisms 10, 1605 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Belzer, C. Nutritional strategies for mucosal health: the interplay between microbes and mucin glycans. Trends Microbiol. 30, 13–21 (2021).

    Article  PubMed  Google Scholar 

  90. Aakko, J. et al. Human milk oligosaccharide categories define the microbiota composition in human colostrum. Benef. Microbes 8, 563–567 (2017).

    Article  CAS  PubMed  Google Scholar 

  91. Bäckhed, F. et al. Dynamics and stabilization of the human gut microbiome during the first year of life. Cell Host Microbe 17, 690–703 (2015).

    Article  PubMed  Google Scholar 

  92. Bergström, A. et al. Establishment of intestinal microbiota during early life: a longitudinal, explorative study of a large cohort of Danish infants. Appl. Env. Microbiol. 80, 2889–2900 (2014).

    Article  Google Scholar 

  93. Azad, M. B. et al. Gut microbiota of healthy Canadian infants: profiles by mode of delivery and infant diet at 4 months. CMAJ 185, 385–394 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  94. Grant, E. T., Boudaud, M., Muller, A., Macpherson, A. J. & Desai, M. S. Maternal diet and gut microbiome composition modulate early‐life immune development. EMBO Mol. Med. 15, e17241 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Gurung, M. et al. Microbiota from human infants consuming secretors or non-secretors mothers’ milk impacts the gut and immune system in mice. mSystems 9, e0029424 (2024).

    Article  PubMed  Google Scholar 

  96. Padilla, L. et al. Mechanism of 2′-fucosyllactose degradation by human-associated Akkermansia. J. Bacteriol. 206, e0033423 (2024).

    Article  PubMed  Google Scholar 

  97. Ribo, S. et al. Increasing breast milk betaine modulates Akkermansia abundance in mammalian neonates and improves long-term metabolic health. Sci. Transl. Med. 13, eabb0322 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Meng, X. et al. A purified aspartic protease from Akkermansia muciniphila plays an important role in degrading Muc2. Int. J. Mol. Sci. 21, 72 (2021).

    Article  Google Scholar 

  99. Shon, D. J., Fernandez, D., Riley, N. M., Ferracane, M. J. & Bertozzi, C. R. Structure-guided mutagenesis of a mucin-selective metalloprotease from Akkermansia muciniphila alters substrate preferences. J. Biol. Chem. 298, 101917 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Shon, D. J. et al. An enzymatic toolkit for selective proteolysis, detection, and visualization of mucin-domain glycoproteins. Proc. Natl Acad. Sci. USA 117, 21299–21307 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Trastoy, B., Naegeli, A., Anso, I., Sjögren, J. & Guerin, M. E. Structural basis of mammalian mucin processing by the human gut O-glycopeptidase OgpA from Akkermansia muciniphila. Nat. Commun. 11, 4844 (2020). This paper characterizes the A. muciniphila O-glycopeptidase OgpA and describes its possible application to map O-glycosylation sites on a protein.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Medley, B. J. et al. A previously uncharacterized O-glycopeptidase from Akkermansia muciniphila requires the Tn-antigen for cleavage of the peptide bond. J. Biol. Chem. 298, 102439 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Espey, M. G. Role of oxygen gradients in shaping redox relationships between the human intestine and its microbiota. Free. Radic. Biol. Med. 55, 130–140 (2013).

    Article  CAS  PubMed  Google Scholar 

  104. Machado, D. et al. Uncovering Akkermansia muciniphila resilience or susceptibility to different temperatures, atmospheres and gastrointestinal conditions. Anaerobe 61, 102135 (2020).

    Article  PubMed  Google Scholar 

  105. Peña-Cearra, A. et al. Akkermansia muciniphila-induced trained immune phenotype increases bacterial intracellular survival and attenuates inflammation. Commun. Biol. 7, 192 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  106. Dawson, P. A. & Karpen, S. J. Intestinal transport and metabolism of bile acids. J. Lipid Res. 56, 1085–1099 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. van der Ark, K. C. H. et al. Encapsulation of the therapeutic microbe Akkermansia muciniphila in a double emulsion enhances survival in simulated gastric conditions. Food Res. Int. 102, 372–379 (2017).

    Article  PubMed  Google Scholar 

  108. Hagi, T., Geerlings, S. Y., Nijsse, B. & Belzer, C. The effect of bile acids on the growth and global gene expression profiles in Akkermansia muciniphila. Appl. Microbiol. Biotechnol. 104, 10641–10653 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Juárez-Fernández, M. et al. The synbiotic combination of Akkermansia muciniphila and quercetin ameliorates early obesity and NAFLD through gut microbiota reshaping and bile acid metabolism modulation. Antioxidants 10, 2001 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  110. Pierre, J. F. et al. Activation of bile acid signaling improves metabolic phenotypes in high-fat diet-induced obese mice. Am. J. Physiol. Gastrointest. Liver Physiol. 311, G286–G304 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  111. Ruas-Madiedo, P., Gueimonde, M., Arigoni, F., de los Reyes-Gavilán, C. G. & Margolles, A. Bile affects the synthesis of exopolysaccharides by Bifidobacterium animalis. Appl. Env. Microbiol. 75, 1204–1207 (2009).

    Article  CAS  Google Scholar 

  112. Fanning, S. et al. Bifidobacterial surface-exopolysaccharide facilitates commensal–host interaction through immune modulation and pathogen protection. Proc. Natl Acad. Sci. USA 109, 2108–2113 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Anhê, F. F. et al. A polyphenol-rich cranberry extract protects from diet-induced obesity, insulin resistance and intestinal inflammation in association with increased Akkermansia spp. population in the gut microbiota of mice. Gut 64, 872–883 (2015).

    Article  PubMed  Google Scholar 

  114. Roopchand, D. E. et al. Dietary polyphenols promote growth of the gut bacterium Akkermansia muciniphila and attenuate high-fat diet-induced metabolic syndrome. Diabetes 64, 2847–2858 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Salem, M. B., El-Lakkany, N. M., Seif el-Din, S. H., Hammam, O. A. & Samir, S. Diosmin alleviates ulcerative colitis in mice by increasing Akkermansia muciniphila abundance, improving intestinal barrier function, and modulating the NF-κB and Nrf2 pathways. Heliyon 10, e27527 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Reider, S. et al. Short- and long-term effects of a prebiotic intervention with polyphenols extracted from European black elderberry—sustained expansion of Akkermansia spp. J. Pers. Med. 12, 1479 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  117. Rodríguez-Daza, M. C. et al. Polyphenol-mediated gut microbiota modulation: toward prebiotics and further. Front. Nutr. 8, 689456 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  118. Rodríguez-Daza, M. C. & de Vos, W. M. Polyphenols as drivers of a homeostatic gut microecology and immuno-metabolic traits of Akkermansia muciniphila: from mouse to man. Int. J. Mol. Sci. 24, 45 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  119. Van Buiten, C. B., Seitz, V. A., Metcalf, J. L. & Raskin, I. Dietary polyphenols support Akkermansia muciniphila growth via mediation of the gastrointestinal redox environment. Antioxidants 13, 304 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  120. Rodríguez-Daza, M.-C. et al. Wild blueberry proanthocyanidins shape distinct gut microbiota profile and influence glucose homeostasis and intestinal phenotypes in high-fat high-sucrose fed mice. Sci. Rep. 10, 2217 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  121. Lu, F. et al. Early-life polyphenol intake promotes Akkermansia growth and increase of host goblet cells in association with the potential synergistic effect of Lactobacillus. Food Res. Int. 149, 110648 (2021).

    Article  CAS  PubMed  Google Scholar 

  122. Plovier, H. et al. A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice. Nat. Med. 23, 107–113 (2016). This study shows that pasteurized A. muciniphila and purified Amuc_1100 induce beneficial metabolic effects in mice.

    Article  PubMed  Google Scholar 

  123. Gao, X. et al. Akkermansia muciniphila-derived small extracellular vesicles attenuate intestinal ischemia–reperfusion-induced postoperative cognitive dysfunction by suppressing microglia activation via the TLR2/4 signaling. Biochim. Biophys. Acta, Mol. Cell Res. 1871, 119630 (2024).

    Article  CAS  PubMed  Google Scholar 

  124. Kikkert, R., Laine, M. L., Aarden, L. A. & Van Winkelhoff, A. J. Activation of Toll‐like receptors 2 and 4 by Gram‐negative periodontal bacteria. Oral. Microbiol. Immunol. 22, 145–151 (2007).

    Article  CAS  PubMed  Google Scholar 

  125. Mandell, L. et al. Intact Gram-negative Helicobacter pylori, Helicobacter felis, and Helicobacter hepaticus bacteria activate innate immunity via Toll-like receptor 2 but not Toll-like receptor 4. Infect. Immun. 72, 6446–6454 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Bae, M. et al. Akkermansia muciniphila phospholipid induces homeostatic immune responses. Nature 608, 168–173 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Akira, S. & Takeda, K. Toll-like receptor signalling. Nat. Rev. Immunol. 4, 499–511 (2004).

    Article  CAS  PubMed  Google Scholar 

  128. Xie, S. et al. Novel tripeptide RKH derived from Akkermansia muciniphila protects against lethal sepsis. Gut 73, 78–91 (2024).

    Article  CAS  Google Scholar 

  129. Yoon, H. S. et al. Akkermansia muciniphila secretes a glucagon-like peptide-1-inducing protein that improves glucose homeostasis and ameliorates metabolic disease in mice. Nat. Microbiol. 6, 563–573 (2021).

    Article  CAS  PubMed  Google Scholar 

  130. Kim, S.-M. et al. Secreted Akkermansia muciniphila threonyl-tRNA synthetase functions to monitor and modulate immune homeostasis. Cell Host Microbe 31, 1021–1037 (2023).

    Article  CAS  PubMed  Google Scholar 

  131. Zhang, Q. et al. Genetic mapping of microbial and host traits reveals production of immunomodulatory lipids by Akkermansia muciniphila in the murine gut. Nat. Microbiol. 8, 424–440 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Seck, E. H. et al. Salt in stools is associated with obesity, gut halophilic microbiota and Akkermansia muciniphila depletion in humans. Int. J. Obes. 43, 862–871 (2019).

    Article  CAS  Google Scholar 

  133. Dao, M. C. et al. Akkermansia muciniphila and improved metabolic health during a dietary intervention in obesity: relationship with gut microbiome richness and ecology. Gut 65, 426–436 (2016).

    Article  CAS  PubMed  Google Scholar 

  134. Santacruz, A. et al. Gut microbiota composition is associated with body weight, weight gain and biochemical parameters in pregnant women. Br. J. Nutr. 104, 83–92 (2010).

    Article  CAS  PubMed  Google Scholar 

  135. Dao, X. M. C. et al. Akkermansia muciniphila abundance is lower in severe obesity, but its increased level after bariatric surgery is not associated with metabolic health improvement. Am. J. Physiol. Endocrinol. Metab. 317, E446–E459 (2019).

    Article  CAS  PubMed  Google Scholar 

  136. Ouwerkerk, J. P., De Vos, W. M. & Belzer, C. Glycobiome: bacteria and mucus at the epithelial interface. Best. Pract. Res. Clin. Gastroenterol. 27, 25–38 (2013).

    Article  CAS  PubMed  Google Scholar 

  137. Schneeberger, M. et al. Akkermansia muciniphila inversely correlates with the onset of inflammation, altered adipose tissue metabolism and metabolic disorders during obesity in mice. Sci. Rep. 5, 16643 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Zhang, J. et al. Decreased abundance of Akkermansia muciniphila leads to the impairment of insulin secretion and glucose homeostasis in lean type 2 diabetes. Adv. Sci. 8, 2100536 (2021).

    Article  CAS  Google Scholar 

  139. Shin, N. R. et al. An increase in the Akkermansia spp. population induced by metformin treatment improves glucose homeostasis in diet-induced obese mice. Gut 63, 727–735 (2014).

    Article  CAS  PubMed  Google Scholar 

  140. Zhao, S. et al. Akkermansia muciniphila improves metabolic profiles by reducing inflammation in chow diet-fed mice. J. Mol. Endocrinol. 58, 1–14 (2017).

    Article  PubMed  Google Scholar 

  141. Wu, F. et al. An Akkermansia muciniphila subtype alleviates high-fat diet-induced metabolic disorders and inhibits the neurodegenerative process in mice. Anaerobe 61, 102138 (2020).

    Article  CAS  PubMed  Google Scholar 

  142. Kim, S. et al. Akkermansia muciniphila prevents fatty liver disease, decreases serum triglycerides, and maintains gut homeostasis. Appl. Env. Microbiol. 86, e03004–e03019 (2020).

    Article  CAS  Google Scholar 

  143. Depommier, C. et al. Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study. Nat. Med. 25, 1096–1103 (2019). This study shows that pasteurized A. muciniphila is safe and tolerated by human subjects.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Lukovac, S. et al. Differential modulation by Akkermansia muciniphila and Faecalibacterium prausnitzii of host peripheral lipid metabolism and histone acetylation in mouse gut organoids. mBio 5, e01438–14 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  145. McLoughlin, R. M. et al. Interplay between IFN-γ and IL-6 signaling governs neutrophil trafficking and apoptosis during acute inflammation. J. Clin. Investig. 112, 598 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Greer, R. L. et al. Akkermansia muciniphila mediates negative effects of IFNγ on glucose metabolism. Nat. Commun. 7, 1–13 (2016).

    Article  Google Scholar 

  147. Davenport, E. R. et al. Genome-wide association studies of the human gut microbiota. PLoS ONE 10, e0140301 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  148. Viera, J. T., El-Merahbi, R., Nieswandt, B., Stegner, D. & Sumara, G. Phospholipases D1 and D2 suppress appetite and protect against overweight. PLoS ONE 11, e0157607 (2016).

    Article  Google Scholar 

  149. Alberts, A. et al. Binding of macrophage receptor MARCO, LDL, and LDLR to disease-associated crystalline structures. Front. Immunol. 11, 596103 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Ansaldo, E. et al. Akkermansia muciniphila induces intestinal adaptive immune responses during homeostasis. Science 364, 1179–1184 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Wu, W. et al. Protective effect of Akkermansia muciniphila against immune-mediated liver injury in a mouse model. Front. Microbiol. 8, 1804 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  152. Kim, S. et al. Mucin degrader Akkermansia muciniphila accelerates intestinal stem cell-mediated epithelial development. Gut Microbes 13, 1892441 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  153. Wang, L. et al. A purified membrane protein from Akkermansia muciniphila or the pasteurised bacterium blunts colitis associated tumourigenesis by modulation of CD8+ T cells in mice. Gut 69, 1988–1997 (2020).

    Article  CAS  PubMed  Google Scholar 

  154. Kang, C. S. et al. Extracellular vesicles derived from gut microbiota, especially Akkermansia muciniphila, protect the progression of dextran sulfate sodium-induced colitis. PLoS ONE 8, e76520 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. Earley, H. et al. The abundance of Akkermansia muciniphila and its relationship with sulphated colonic mucins in health and ulcerative colitis. Sci. Rep. 9, 15683 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  156. Kang, E.-J. et al. The secreted protein Amuc_1409 from Akkermansia muciniphila improves gut health through intestinal stem cell regulation. Nat. Commun. 15, 2983 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. Podolsky, D. K., Gerken, G., Eyking, A. & Cario, E. Colitis-associated variant of TLR2 causes impaired mucosal repair because of TFF3 deficiency. Gastroenterology 137, 209–220 (2009).

    Article  CAS  PubMed  Google Scholar 

  158. Cario, E., Gerken, G. & Podolsky, D. K. Toll-like receptor 2 controls mucosal inflammation by regulating epithelial barrier function. Gastroenterology 132, 1359–1374 (2007).

    Article  CAS  PubMed  Google Scholar 

  159. Desai, M. S. et al. A dietary fiber-deprived gut microbiota degrades the colonic mucus barrier and enhances pathogen susceptibility. Cell 167, 1339–1353 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  160. Kuffa, P. et al. Fiber-deficient diet inhibits colitis through the regulation of the niche and metabolism of a gut pathobiont. Cell Host Microbe 31, 2007–2022 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  161. Parrish, A. et al. Akkermansia muciniphila exacerbates food allergy in fibre-deprived mice. Nat. Microbiol. 8, 1863–1879 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  162. Wolter, M. et al. Diet-driven differential response of Akkermansia muciniphila modulates pathogen susceptibility. Mol. Syst. Biol. 20, 596–625 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  163. Shono, Y. et al. Increased GVHD-related mortality with broad-spectrum antibiotic use after allogeneic hematopoietic stem cell transplantation in human patients and mice. Sci. Transl. Med. 8, 339ra71 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  164. Konstanti, P. et al. Physiology of γ-aminobutyric acid production by Akkermansia muciniphila. Appl. Env. Microbiol. 90, e0112123 (2024).

    Article  Google Scholar 

  165. Yunes, R. A. et al. GABA production and structure of gadB/gadC genes in Lactobacillus and Bifidobacterium strains from human microbiota. Anaerobe 42, 197–204 (2016).

    Article  CAS  PubMed  Google Scholar 

  166. Olson, C. A. et al. The gut microbiota mediates the anti-seizure effects of the ketogenic diet. Cell 173, 1728–1741 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. Li, Z. et al. Multi-omics analyses of serum metabolome, gut microbiome and brain function reveal dysregulated microbiota–gut–brain axis in bipolar depression. Mol. Psychiatry 27, 4123–4135 (2022).

    Article  CAS  PubMed  Google Scholar 

  168. Xi, W. et al. Depicting the composition of gut microbiota in children with tic disorders: an exploratory study. J. Child. Psychol. Psychiatry 62, 1246–1254 (2021).

    Article  PubMed  Google Scholar 

  169. Fang, X., Li, F. J. & Hong, D. J. Potential role of Akkermansia muciniphila in Parkinson’s disease and other neurological/autoimmune diseases. Curr. Med. Sci. 41, 1172–1177 (2021).

    Article  PubMed  Google Scholar 

  170. Cox, L. M. et al. The gut microbiome in progressive multiple sclerosis. Ann. Neurol. 89, 1195–1211 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  171. Blacher, E. et al. Potential roles of gut microbiome and metabolites in modulating ALS in mice. Nature 572, 474–480 (2019).

    Article  CAS  PubMed  Google Scholar 

  172. Chia, L. W. et al. Deciphering the trophic interaction between Akkermansia muciniphila and the butyrogenic gut commensal Anaerostipes caccae using a metatranscriptomic approach. Antonie Van. Leeuwenhoek 111, 859–873 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  173. Pichler, M. J. et al. Butyrate producing colonic clostridiales metabolise human milk oligosaccharides and cross feed on mucin via conserved pathways. Nat. Commun. 11, 3285 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  174. Shetty, S. A. et al. Dynamic metabolic interactions and trophic roles of human gut microbes identified using a minimal microbiome exhibiting ecological properties. ISME J. 16, 2144–2159 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  175. Arumugam, M. et al. Enterotypes of the human gut microbiome. Nature 473, 174–180 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  176. Derrien, M., Belzer, C. & de Vos, W. M. Akkermansia muciniphila and its role in regulating host functions. Microb. Pathog. 106, 171–181 (2017).

    Article  PubMed  Google Scholar 

  177. Rasmussen, T. S. et al. Fecal virome transfer improves proliferation of commensal gut Akkermansia muciniphila and unexpectedly enhances the fertility rate in laboratory mice. Gut Microbes 15, 2208504 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  178. Yang, W., Ao, M., Hu, Y., Li, Q. K. & Zhang, H. Mapping the O‐glycoproteome using site‐specific extraction of O‐linked glycopeptides (EXoO). Mol. Syst. Biol. 14, e8486 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  179. Yang, S. et al. Deciphering protein O-glycosylation: solid-phase chemoenzymatic cleavage and enrichment. Anal. Chem. 90, 8261–8269 (2018).

    Article  CAS  PubMed  Google Scholar 

  180. King, S. L. et al. Characterizing the O-glycosylation landscape of human plasma, platelets, and endothelial cells. Blood Adv. 1, 429–442 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  181. Ma, C. et al. Comprehensive N- and O-glycosylation mapping of human coagulation factor V. J. Thromb. Haemost. 18, 1884–1892 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  182. Lombard, V., Golaconda Ramulu, H., Drula, E., Coutinho, P. M. & Henrissat, B. The carbohydrate-active enzymes database (CAZy) in 2013. Nucleic Acids Res. 42, 490–495 (2014).

    Article  Google Scholar 

  183. Turck, D. et al. Safety of pasteurised Akkermansia muciniphila as a novel food pursuant to Regulation (EU) 2015/2283. EFSA J. 19, e06780 (2021).

    PubMed  PubMed Central  Google Scholar 

  184. Yang, J. et al. Disparate metabolic responses in mice fed a high-fat diet supplemented with maize-derived non-digestible feruloylated oligo and polysaccharides are linked to changes in the gut microbiota. PLoS ONE 11, e0146144 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  185. Song, H. et al. Red pitaya betacyanins protects from diet-induced obesity, liver steatosiaand insulin resistance in association with modulation of gut microbiota in mice. J. Gastroenterol. Hepatol. 31, 1462–1469 (2016).

    Article  CAS  PubMed  Google Scholar 

  186. Gómez-Gallego, C. et al. Infant formula supplemented with polyamines alters the intestinal microbiota in neonatal BALB/cOlaHsd mice. J. Nutr. Biochem. 23, 1508–1513 (2012).

    Article  PubMed  Google Scholar 

  187. Andersson, K. E. et al. Diverse effects of oats on cholesterol metabolism in C57BL/6 mice correlate with expression of hepatic bile acid-producing enzymes. Eur. J. Nutr. 52, 1755–1769 (2013).

    Article  CAS  PubMed  Google Scholar 

  188. Everard, A. et al. Responses of gut microbiota and glucose and lipid metabolism to prebiotics in genetic obese and diet-induced leptin-resistant mice. Diabetes 60, 2775–2786 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  189. Li, L. et al. Function and therapeutic prospects of next-generation probiotic Akkermansia muciniphila in infectious diseases. Front. Microbiol. 15, 1354447 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  190. Jia, B., Zou, Y., Han, X., Bae, J.-W. & Jeon, C. O. Gut microbiome-mediated mechanisms for reducing cholesterol levels: implications for ameliorating cardiovascular disease. Trends Microbiol. 31, 76–91 (2023).

    Article  CAS  PubMed  Google Scholar 

  191. Hasani, A. et al. The role of Akkermansia muciniphila in obesity, diabetes and atherosclerosis. J. Med. Microbiol. 70, 001435 (2021).

    Article  Google Scholar 

  192. Wang, L. & Tang, D. Akkermania muciniphila: a rising star in tumor immunology. Clin. Transl. Oncol. https://doi.org/10.1007/s12094-024-03493-6 (2024).

  193. Pellegrino, A., Coppola, G., Santopaolo, F., Gasbarrini, A. & Ponziani, F. R. Role of Akkermansia in human diseases: from causation to therapeutic properties. Nutrients 15, 1815 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  194. Jensen, M. et al. Akkermansia muciniphila exoglycosidases target extended blood group antigens to generate ABO-universal blood. Nat. Microbiol. 9, 1176–1188 (2024).

    Article  CAS  PubMed  Google Scholar 

  195. Anso, I. et al. Turning universal O into rare Bombay type blood. Nat. Commun. 14, 1765 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  196. Chua, H.-H. et al. Antagonism between gut Ruminococcus gnavus and Akkermansia muciniphila modulates the progression of chronic hepatitis B. Cell Mol. Gastroenterol. Hepatol. 17, 361–381 (2024).

    Article  CAS  PubMed  Google Scholar 

  197. Liu, Y.-F. et al. Astaxanthin alleviates chronic prostatitis/chronic pelvic pain syndrome by increasing colonization of Akkermansia muciniphila in the intestine. Phytomedicine 123, 155249 (2024).

    Article  CAS  PubMed  Google Scholar 

  198. Qiao, C.-M. et al. Akkermansia muciniphila is beneficial to a mouse model of Parkinson’s disease, via alleviated neuroinflammation and promoted neurogenesis, with involvement of SCFAs. Brain Sci. 14, 238 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  199. Guo, H., Liu, X., Chen, T., Wang, X. & Zhang, X. Akkermansia muciniphila improves depressive-like symptoms by modulating the level of 5-HT neurotransmitters in the gut and brain of mice. Mol. Neurobiol. 61, 821–834 (2024).

    Article  CAS  PubMed  Google Scholar 

  200. Kim, J. Y. et al. Akkermansia muciniphila extracellular vesicles have a protective effect against hypertension. Hypertens. Res. 47, 1642–1653 (2024).

    Article  CAS  PubMed  Google Scholar 

  201. Ou, Z. et al. Protective effects of Akkermansia muciniphila on cognitive deficits and amyloid pathology in a mouse model of Alzheimer’s disease. Nutr. Diabetes 10, 12 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  202. Ding, Y. et al. A next-generation probiotic: Akkermansia muciniphila ameliorates chronic stress-induced depressive-like behavior in mice by regulating gut microbiota and metabolites. Appl. Microbiol. Biotechnol. 105, 8411–8426 (2021).

    Article  CAS  PubMed  Google Scholar 

  203. DeSana, A. J., Estus, S., Barrett, T. A. & Saatman, K. E. Acute gastrointestinal permeability after traumatic brain injury in mice precedes a bloom in Akkermansia muciniphila supported by intestinal hypoxia. Sci. Rep. 14, 2990 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  204. Hammer, T. J. Why do hosts malfunction without microbes? Missing benefits versus evolutionary addiction. Trends Microbiol. 32, 132–141 (2024).

    Article  CAS  PubMed  Google Scholar 

  205. Kobayashi, Y., Kawahara, T., Inoue, S. & Kohda, N. Akkermansia biwaensis sp. nov., an anaerobic mucin-degrading bacterium isolated from human faeces. Int. J. Syst. Evol. Microbiol. 73, https://doi.org/10.1099/ijsem.0.005697 (2023).

  206. Gilroy, R. et al. Extensive microbial diversity within the chicken gut microbiome revealed by metagenomics and culture. PeerJ 9, e10941 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  207. Richter, M. & Rosselló-Móra, R. Shifting the genomic gold standard for the prokaryotic species definition. Proc. Natl Acad. Sci. USA 106, 19126–19131 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  208. Becken, B. et al. Genotypic and phenotypic diversity among human isolates of Akkermansia muciniphila. mBio 12, 00478–21 (2021).

    Article  Google Scholar 

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Acknowledgements

The authors acknowledge the Netherlands Ministry of Education, Culture and Science and the Dutch Research Council (NWO) for the funding through the Soehngen Institute of Anaerobic Microbiology (SIAM) Gravitation Grant (grant number 0.24.002.002) and through the Green Top Sectors Grant (GSGT.2019.002).

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    Athanasia Ioannou, Maryse D. Berkhout, Sharon Y. Geerlings & Clara Belzer

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Ioannou, A., Berkhout, M.D., Geerlings, S.Y. et al. Akkermansia muciniphila: biology, microbial ecology, host interactions and therapeutic potential. Nat Rev Microbiol 23, 162–177 (2025). https://doi.org/10.1038/s41579-024-01106-1

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