Action and function of Akkermansia muciniphila in microbiome ecology, health and disease

Best Practice and Research: Clinical Gastroenterology

Volumn 31, Issue 6, 2017, Pages 637-642

  Ottman, Noora ^b   Geerlings, Sharon Y ^a   Aalvink, Steven ^a   de Vos, Willem M ^a,c   Belzer, Clara ^a  

^a WAGENINGEN UNIVERSITY   (Netherlands)

^b KAROLINSKA INSTITUTE   (Sweden)

^c UNIVERSITY OF HELSINKI   (Finland)

Author keywords

Akkermansia muciniphila; Microbiome; Mucus; Pharmabiotic; Probiotic

Indexed keywords

MUCIN; PROTEOME; SHORT CHAIN FATTY ACID; TRANSCRIPTOME;

AKKERMANSIA MUCINIPHILA; BACTERIAL OUTER MEMBRANE; ECOLOGY; GRAM NEGATIVE BACTERIUM; HEALTH STATUS; HUMAN; IMMUNITY; INTESTINE FLORA; MICROBIOME; NONHUMAN; REVIEW; DISEASES; GROWTH, DEVELOPMENT AND AGING; IMMUNOLOGY; MICROFLORA; PATHOGENICITY; VERRUCOMICROBIA;

DISEASE; HUMANS; MICROBIOTA; VERRUCOMICROBIA;

EID: 85033689965     PISSN: 15216918     EISSN: 15321916     Source Type: Journal    
DOI: 10.1016/j.bpg.2017.10.001     Document Type: Review

References (76)

1. Gerritsen, J., Smidt, H., Rijkers, G.T., de Vos, W.M., et al. Intestinal microbiota in human health and disease: the impact of probiotics. Genes Nutr 6 (2011), 209–240.
2. Belkaid, Y., Hand, T.W., et al. Role of the microbiota in immunity and inflammation. Cell 157 (2014), 121–141.
3. Duerr, C.U., Hornef, M.W., et al. The mammalian intestinal epithelium as integral player in the establishment and maintenance of host-microbial homeostasis. Semin Immunol 24 (2012), 25–35.
4. Ouwerkerk, J.P., de Vos, W.M., Belzer, C., et al. Glycobiome: bacteria and mucus at the epithelial interface. Best Pract Res Clin Gastroenterol 27 (2013), 25–38.
5. Koropatkin, N.M., Cameron, E.A., Martens, E.C., et al. How glycan metabolism shapes the human gut microbiota. Nat Rev Microbiol 10 (2012), 323–335.
6. Everard, A., Belzer, C., Geurts, L., Ouwerkerk, J.P., Druart, C., Bindels, L.B., et al. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proc Natl Acad Sci U. S. A 110 (2013), 9066–9071.
7. Plovier, H., Everard, A., Druart, C., Depommier, C., Van Hul, M., Geurts, L., et al. A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice. Nat Med 23 (2017), 107–113.
8. Belzer, C., Chia, L., Aalvink, S., Chamlagain, B.V.P., de Vos, W.M., et al. Microbial metabolic networks at the mucus layer lead to diet independent butyrate -and vitamin B12 production by intestinal symbionts. 2017.
9. Derrien, M., Vaughan, E.E., Plugge, C.M., de Vos, W.M., et al. Akkermansia muciniphila gen. nov., sp. nov., a human intestinal mucin-degrading bacterium. Int J Syst Evol Microbiol 54 (2004), 1469–1476.
10. Rooijers, K., Kolmeder, C., Juste, C., Dore, J., de Been, M., Boeren, S., et al. An iterative workflow for mining the human intestinal metaproteome. BMC Genomics, 12, 2011, 6.
11. Collado, M.C., Derrien, M., Isolauri, E., de Vos, W.M., Salminen, S., et al. Intestinal integrity and Akkermansia muciniphila, a mucin-degrading member of the intestinal microbiota present in infants, adults, and the elderly. Appl Environ Microbiol 73 (2007), 7767–7770.
12. Derrien, M., Collado, M.C., Ben-Amor, K., Salminen, S., de Vos, W.M., et al. The mucin degrader Akkermansia muciniphila is an abundant resident of the human intestinal tract. Appl Environ Microbiol 74 (2008), 1646–1648.
13. Png, C.W., Linden, S.K., Gilshenan, K.S., Zoetendal, E.G., McSweeney, C.S., Sly, L.I., et al. Mucolytic bacteria with increased prevalence in IBD mucosa augment in vitro utilization of mucin by other bacteria. Am J Gastroenterol 105 (2010), 2420–2428.
14. Lyra, A., Forssten, S., Rolny, P., Wettergren, Y., Lahtinen, S.J., Salli, K., et al. Comparison of bacterial quantities in left and right colon biopsies and faeces. World J Gastroenterol 18 (2012), 4404–4411.
15. Rajilic-Stojanovic, M., Shanahan, F., Guarner, F., de Vos, W.M., et al. Phylogenetic analysis of dysbiosis in ulcerative colitis during remission. Inflamm Bowel Dis 19 (2013), 481–488.
16. Swidsinski, A., Dorffel, Y., Loening-Baucke, V., Theissig, F., Ruckert, J.C., Ismail, M., et al. Acute appendicitis is characterised by local invasion with Fusobacterium nucleatum/necrophorum. Gut 60 (2011), 34–40.
17. Karlsson, C.L., Onnerfalt, J., Xu, J., Molin, G., Ahrne, S., Thorngren-Jerneck, K., et al. The microbiota of the gut in preschool children with normal and excessive body weight. Obes (Silver Spring) 20 (2012), 2257–2261.
18. Dao, M.C., Everard, A., Aron-Wisnewsky, J., Sokolovska, N., Prifti, E., Verger, E.O., et al. Akkermansia muciniphila and improved metabolic health during a dietary intervention in obesity: relationship with gut microbiome richness and ecology. Gut 65 (2016), 426–436.
19. Zhang, X., Shen, D., Fang, Z., Jie, Z., Qiu, X., Zhang, C., et al. Human gut microbiota changes reveal the progression of glucose intolerance. PLoS One, 8, 2013, e71108.
20. Ottman, N., Reunanen, J., Meijerink, M., Pietila, T.E., Kainulainen, V., Klievink, J., et al. Pili-like proteins of Akkermansia muciniphila modulate host immune responses and gut barrier function. PLoS One, 12, 2017, e0173004.
21. Neef, A., Sanz, Y., et al. Future for probiotic science in functional food and dietary supplement development. Curr Opin Clin Nutr Metab Care 16 (2013), 679–687.
22. O'Toole, P.W., Marchesi, J.R., Hill, C., et al. Next-generation probiotics: the spectrum from probiotics to live biotherapeutics. Nat Microbiol, 2, 2017, 17057.
23. van Passel, M.W., Kant, R., Zoetendal, E.G., Plugge, C.M., Derrien, M., Malfatti, S.A., et al. The genome of Akkermansia muciniphila, a dedicated intestinal mucin degrader, and its use in exploring intestinal metagenomes. PLoS One, 6, 2011, e16876.
24. Rogers, T.E., Pudlo, N.A., Koropatkin, N.M., Bell, J.S., Moya Balasch, M., Jasker, K., et al. Dynamic responses of Bacteroides thetaiotaomicron during growth on glycan mixtures. Mol Microbiol 88 (2013), 876–890.
25. Ouwerkerk, J.P., et al. Akkermansia species - phylogeny, physiology and comparative genomics. 2016.
26. Puertollano, E., Kolida, S., Yaqoob, P., et al. Biological significance of short-chain fatty acid metabolism by the intestinal microbiome. Curr Opin Clin Nutr Metab Care 17 (2014), 139–144.
27. Desai, M.S., Seekatz, A.M., Koropatkin, N.M., Kamada, N., Hickey, C.A., Wolter, M., et al. A dietary fiber-deprived gut microbiota degrades the colonic mucus barrier and enhances pathogen susceptibility. Cell 167 (2016), 1339–1353 e1321.
28. Mack, I., Cuntz, U., Gramer, C., Niedermaier, S., Pohl, C., Schwiertz, A., et al. Weight gain in anorexia nervosa does not ameliorate the faecal microbiota, branched chain fatty acid profiles, and gastrointestinal complaints. Sci Rep, 6, 2016, 26752.
29. Louis, S., Tappu, R.M., Damms-Machado, A., Huson, D.H., Bischoff, S.C., et al. Characterization of the gut microbial community of obese patients following a weight-loss intervention using whole metagenome shotgun sequencing. PLoS One, 11, 2016, e0149564.
30. Everard, A., Lazarevic, V., Derrien, M., Girard, M., Muccioli, G.G., Neyrinck, A.M., et al. Responses of gut microbiota and glucose and lipid metabolism to prebiotics in genetic obese and diet-induced leptin-resistant mice. Diabetes 60 (2011), 2775–2786.
31. Ottman, N., Davids, M., Suarez-Diez, M., Boeren, S., Schaap, P.J., Martins dos Santos, V.A.P., et al. Genome-scale model and omics analysis of metabolic capacities of Akkermansia muciniphila reveal a preferential mucin-degrading lifestyle. Appl Environ Microbiol, 83(18), 2017, 10.1128/AEM.01014-17.
32. Schrager, J., et al. The chemical composition and function of gastrointestinal mucus. Gut 11 (1970), 450–456.
33. Ottman, N., Huuskonen, L., Reunanen, J., Boeren, S., Klievink, J., Smidt, H., et al. Characterization of outer membrane proteome of Akkermansia muciniphila reveals sets of novel proteins exposed to the human intestine. Front Microbiol, 7, 2016, 1157.
34. Lee, K.C., Webb, R.I., Janssen, P.H., Sangwan, P., Romeo, T., Staley, J.T., et al. Phylum Verrucomicrobia representatives share a compartmentalized cell plan with members of bacterial phylum Planctomycetes. BMC Microbiol, 9, 2009, 5.
35. Reunanen, J., Kainulainen, V., Huuskonen, L., Ottman, N., Belzer, C., Huhtinen, H., et al. Akkermansia muciniphila adheres to enterocytes and strengthens the integrity of the epithelial cell layer. Appl Environ Microbiol 81 (2015), 3655–3662.
36. Ouwerkerk, J.P., van der Ark, K.C., Davids, M., Claassens, N.J., Robert Finestra, T., de Vos, W.M., et al. Adaptation of Akkermansia muciniphila to the oxic-anoxic interface of the mucus layer. Appl Environ Microbiol, 2016, 10.1128/AEM.01641–16.
37. Berry, D., Stecher, B., Schintlmeister, A., Reichert, J., Brugiroux, S., Wild, B., et al. Host-compound foraging by intestinal microbiota revealed by single-cell stable isotope probing. Proc Natl Acad Sci U. S. A 110 (2013), 4720–4725.
38. Johansson, M.E., Larsson, J.M., Hansson, G.C., et al. The two mucus layers of colon are organized by the MUC2 mucin, whereas the outer layer is a legislator of host-microbial interactions. Proc Natl Acad Sci U. S. A 108:Suppl 1 (2011), 4659–4665.
39. Johansson, M.E., Phillipson, M., Petersson, J., Velcich, A., Holm, L., Hansson, G.C., et al. The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria. Proc Natl Acad Sci U. S. A 105 (2008), 15064–15069.
40. Moran, A.P., Gupta, A., Joshi, L., et al. Sweet-talk: role of host glycosylation in bacterial pathogenesis of the gastrointestinal tract. Gut 60 (2011), 1412–1425.
41. Tailford, L.E., Crost, E.H., Kavanaugh, D., Juge, N., et al. Mucin glycan foraging in the human gut microbiome. Front Genet, 6, 2015, 81.
42. Derrien, M., van Passel, M.W., van de Bovenkamp, J.H., Schipper, R.G., de Vos, W.M., Dekker, J., et al. Mucin-bacterial interactions in the human oral cavity and digestive tract. Gut Microbes 1 (2010), 254–268.
43. Backhed, F., Ley, R.E., Sonnenburg, J.L., Peterson, D.A., Gordon, J.I., et al. Host-bacterial mutualism in the human intestine. Science 307 (2005), 1915–1920.
44. Xu, J., Bjursell, M.K., Himrod, J., Deng, S., Carmichael, L.K., Chiang, H.C., et al. A genomic view of the human-Bacteroides thetaiotaomicron symbiosis. Science 299 (2003), 2074–2076.
45. Ng, K.M., Ferreyra, J.A., Higginbottom, S.K., Lynch, J.B., Kashyap, P.C., Gopinath, S., et al. Microbiota-liberated host sugars facilitate post-antibiotic expansion of enteric pathogens. Nature 502 (2013), 96–99.
46. Hooper, L.V., Macpherson, A.J., et al. Immune adaptations that maintain homeostasis with the intestinal microbiota. Nat Rev Immunol 10 (2010), 159–169.
47. Robinson, L.S., Lewis, W.G., Lewis, A.L., et al. The sialate O-acetylesterase EstA from gut Bacteroidetes species enables sialidase-mediated cross-species foraging of 9-O-acetylated sialoglycans. J Biol Chem, 2017, 10.1074/jbc.M116.769232.
48. Van den Abbeele, P., Belzer, C., Goossens, M., Kleerebezem, M., De Vos, W.M., Thas, O., et al. Butyrate-producing Clostridium cluster XIVa species specifically colonize mucins in an in vitro gut model. ISME J 7 (2013), 949–961.
49. Lopez-Siles, M., Khan, T.M., Duncan, S.H., Harmsen, H.J., Garcia-Gil, L.J., Flint, H.J., et al. Cultured representatives of two major phylogroups of human colonic Faecalibacterium prausnitzii can utilize pectin, uronic acids, and host-derived substrates for growth. Appl Environ Microbiol 78 (2012), 420–428.
50. Chen, L., Wang, W., Zhou, R., Ng, S.C., Li, J., Huang, M., et al. Characteristics of fecal and mucosa-associated microbiota in Chinese patients with inflammatory bowel disease, vol. 93, 2014, e51 Medicine (Baltimore).
51. Thibault, R., Blachier, F., Darcy-Vrillon, B., de Coppet, P., Bourreille, A., Segain, J.P., et al. Butyrate utilization by the colonic mucosa in inflammatory bowel diseases: a transport deficiency. Inflamm Bowel Dis 16 (2010), 684–695.
52. Koh, A., De Vadder, F., Kovatcheva-Datchary, P., Backhed, F., et al. From dietary fiber to host physiology: short-chain fatty acids as key bacterial metabolites. Cell 165 (2016), 1332–1345.
53. Gaudier, E., Jarry, A., Blottiere, H.M., de Coppet, P., Buisine, M.P., Aubert, J.P., et al. Butyrate specifically modulates MUC gene expression in intestinal epithelial goblet cells deprived of glucose. Am J Physiol Gastrointest Liver Physiol 287 (2004), G1168–G1174.
54. Ottman, N., Davids, M., Suarez-Diez, M., Boeren, S., Schaap, P.J., Martins Dos Santos, V.A.P., et al. Genome-scale model and omics analysis of metabolic capacities of Akkermansia muciniphila reveal a preferential mucin-degrading lifestyle. Appl Environ Microbiol, 2017, 10.1128/AEM.01014-01017.
55. Engels, C., Ruscheweyh, H.J., Beerenwinkel, N., Lacroix, C., Schwab, C., et al. The common gut microbe Eubacterium hallii also contributes to intestinal propionate formation. Front Microbiol, 7, 2016.
56. Derrien, M., et al. Mucin utilisation and host interactions of the novel intestinal microbe Akkermansia muciniphila. (Ph D), 2007, Wageningen Universiteit, Wageningen.
57. Nava, G.M., Carbonero, F., Croix, J.A., Greenberg, E., Gaskins, H.R., et al. Abundance and diversity of mucosa-associated hydrogenotrophic microbes in the healthy human colon. ISME J 6 (2012), 57–70.
58. Willis, C.L., Cummings, J.H., Neale, G., Gibson, G.R., et al. In vitro effects of mucin fermentation on the growth of human colonic sulphate-reducing bacteria. Anaerobe 2 (1996), 117–122.
59. Loubinoux, J., Bronowicki, J.P., Pereira, I.A.C., Mougenel, J.L., Le Faou, A.E., et al. Sulfate-reducing bacteria in human feces and their association with inflammatory bowel diseases. Fems Microbiol Ecol 40 (2002), 107–112.
60. Ijssennagger, N., van der Meer, R., van Mil, S.W.C., et al. Sulfide as a mucus barrier-breaker in inflammatory bowel disease?. Trends Mol Med 22 (2016), 190–199.
61. Kimura, H., et al. Signaling of hydrogen sulfide and polysulfides. Antioxid Redox Signal 22 (2015), 347–349.
62. Ouwerkerk, J.P., Aalvink, S., Belzer, C., De Vos, W.M., et al. Preparation and preservation of viable Akkermansia muciniphila cells for therapeutic interventions. Benef Microbes 8 (2017), 163–169.
63. van der Ark, K.C.H., van Heck, R.G.A., Martins Dos Santos, V.A.P., Belzer, C., de Vos, W.M., et al. More than just a gut feeling: constraint-based genome-scale metabolic models for predicting functions of human intestinal microbes. Microbiome, 5, 2017, 78.
64. Shin, N.R., Lee, J.C., Lee, H.Y., Kim, M.S., Whon, T.W., Lee, M.S., et al. An increase in the Akkermansia spp. population induced by metformin treatment improves glucose homeostasis in diet-induced obese mice. Gut 63 (2014), 727–735.
65. Nobel, Y.R., Cox, L.M., Kirigin, F.F., Bokulich, N.A., Yamanishi, S., Teitler, I., et al. Metabolic and metagenomic outcomes from early-life pulsed antibiotic treatment. Nat Commun, 6, 2015, 7486.
66. Cox, L.M., Yamanishi, S., Sohn, J., Alekseyenko, A.V., Leung, J.M., Cho, I., et al. Altering the intestinal microbiota during a critical developmental window has lasting metabolic consequences. Cell 158 (2014), 705–721.
67. Lukovac, S., Belzer, C., Pellis, L., Keijser, B.J., de Vos, W.M., Montijn, R.C., et al. Differential modulation by Akkermansia muciniphila and Faecalibacterium prausnitzii of host peripheral lipid metabolism and histone acetylation in mouse gut organoids. MBio, 5, 2014.
68. Lee, H., Ko, G., et al. Effect of metformin on metabolic improvement and gut microbiota. Appl Environ Microbiol 80 (2014), 5935–5943.
69. Qin, J., Li, Y., Cai, Z., Li, S., Zhu, J., Zhang, F., et al. A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature 490 (2012), 55–60.
70. Brahe, L.K., Le Chatelier, E., Prifti, E., Pons, N., Kennedy, S., Hansen, T., et al. Specific gut microbiota features and metabolic markers in postmenopausal women with obesity. Nutr Diabetes, 5, 2015, e159.
71. Loonen, L.M., Stolte, E.H., Jaklofsky, M.T., Meijerink, M., Dekker, J., van Baarlen, P., et al. REG3gamma-deficient mice have altered mucus distribution and increased mucosal inflammatory responses to the microbiota and enteric pathogens in the ileum. Mucosal Immunol 7 (2014), 939–947.
72. Van den Abbeele, P., Gerard, P., Rabot, S., Bruneau, A., El Aidy, S., Derrien, M., et al. Arabinoxylans and inulin differentially modulate the mucosal and luminal gut microbiota and mucin-degradation in humanized rats. Environ Microbiol 13 (2011), 2667–2680.
73. Li, J., Lin, S., Vanhoutte, P.M., Woo, C.W., Xu, A., et al. Akkermansia muciniphila protects against atherosclerosis by preventing metabolic endotoxemia-induced inflammation in apoe-/- mice. Circulation 133 (2016), 2434–2446.
74. Derrien, M., Van Baarlen, P., Hooiveld, G., Norin, E., Muller, M., de Vos, W.M., et al. Modulation of mucosal immune response, tolerance, and proliferation in mice colonized by the mucin-degrader Akkermansia muciniphila. Front Microbiol, 2, 2011, 166.
75. Alexander, K.L., Targan, S.R., Elson, C.O. 3rd, et al. Microbiota activation and regulation of innate and adaptive immunity. Immunol Rev 260 (2014), 206–220.
76. Kau, A.L., Planer, J.D., Liu, J., Rao, S., Yatsunenko, T., Trehan, I., et al. Functional characterization of IgA-targeted bacterial taxa from undernourished Malawian children that produce diet-dependent enteropathy. Sci Transl Med, 7, 2015 276ra224.