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Mucin glycans and their degradation by gut microbiota

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Abstract

The human intestinal tract is inhabited by a tremendous number of microorganisms, which are collectively termed “the gut microbiota”. The intestinal epithelium is covered with a dense layer of mucus that prevents penetration of the gut microbiota into underlying tissues of the host. Recent studies have shown that the maturation and function of the mucus layer are strongly influenced by the gut microbiota, and alteration in the structure and function of the gut microbiota is implicated in several diseases. Because the intestinal mucus layer is at a crucial interface between microbes and their host, its breakdown leads to gut bacterial invasion that can eventually cause inflammation and infection. The mucus is composed of mucin, which is rich in glycans, and the various structures of the complex carbohydrates of mucins can select for distinct mucosa-associated bacteria that are able to bind mucin glycans, and sometimes degrade them as a nutrient source. Mucin glycans are diverse molecules, and thus mucin glycan degradation is a complex process that requires a broad range of glycan-degrading enzymes. Because of the increased recognition of the role of mucus-associated microbes in human health, how commensal bacteria degrade and use host mucin glycans has become of increased interest. This review provides an overview of the relationships between the mucin glycan of the host and gut commensal bacteria, with a focus on mucin degradation.

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References

  1. Bansil, R., Turner, B.S.: The biology of mucus: composition, synthesis and organization. Adv. Drug Deliv. Rev. 124, 3–15 (2018). https://doi.org/10.1016/j.addr.2017.09.023

    Article  CAS  PubMed  Google Scholar 

  2. Ballester, B., Milara, J., Cortijo, J.: Mucins as a new frontier in pulmonary fibrosis. J. Clin. Med. 8, 1447 (2019). https://doi.org/10.3390/jcm8091447

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Johansson, M.E.V., Hansson, G.C.: Immunological aspects of intestinal mucus and mucins. Nat. Rev. Immunol. 16, 639–649 (2016). https://doi.org/10.1038/nri.2016.88

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Pelaseyed, T., Hansson, G.C.: Membrane mucins of the intestine at a glance. J. Cell Sci. 133, jcs240929 (2020). https://doi.org/10.1242/jcs.240929

  5. Linden, S.K., Sutton, P., Karlsson, N.G., Korolik, V., McGuckin, M.A.: Mucins in the mucosal barrier to infection. Mucosal Immunol. 1, 183–197 (2008)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Alemao, C.A., Budden, K.F., Gomez, H.M., Rehman, S.F., Marshall, J.E., Shukla, S.D., Donovan, C., Foster, S.C., Yang, I.A., Keely, S., Mann, E.R., El Omar, E.M., Belz, G.T., Hansbro, P.M.: Impact of diet and the bacterial microbiome on the mucous barrier and immune disorders. Allergy 76, 714–734 (2021). https://doi.org/10.1111/all.1454

    Article  PubMed  Google Scholar 

  7. Hansson, G.C.: Mucins and the microbiome. Annu. Rev. Biochem. 89, 769–793 (2020). https://doi.org/10.1146/annurev-biochem-011520-105053

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Arike, L., Hansson, G.C.: The densely O-glycosylated MUC2 mucin protects the intestine and provides food for the commensal bacteria. J. Mol. Biol. 428, 3221–3229 (2016). https://doi.org/10.1016/j.jmb.2016.02.010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Bergstrom, K.S.B., Xia, L.: Mucin-type O-glycans and their roles in intestinal homeostasis. Glycobiology 23, 1026–1037 (2013). https://doi.org/10.1093/glycob/cwt045

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Sommer, F., Adam, N., Johansson, M.E., Xia, L., Hansson, G.C., Backhed, F.: Altered mucus glycosylation in core 1 O-glycan-deficient mice affects microbiota composition and intestinal architecture. PLoS One 9, e85254 (2014). https://doi.org/10.1371/journal.pone.0085254

  11. Morrison, D.J., Preston, T.: Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism. Gut Microbes 7, 189–200 (2016). https://doi.org/10.1080/19490976.2015.1134082

    Article  PubMed  PubMed Central  Google Scholar 

  12. Koropatkin, N.M., Cameron, E.A., Martens, E.C.: How glycan metabolism shapes the human gut microbiota. Nat. Rev. Microbiol. 10, 323–335 (2012). https://doi.org/10.1038/nrmicro2746

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Etienne-Mesmin, L., Chassaing, B., Desvaux, M., Paepe, K.D., Gresse, R., Sauvaitre, T., Forano, E., Van de Wiele, T., Schüller, S., Juge, N., Blanquet-Diot, S.: Experimental models to study intestinal microbes-mucus interactions in health and disease. FEMS Microbiol. Rev. 43, 457–489 (2019). https://doi.org/10.1093/femsre/fuz013

    Article  CAS  PubMed  Google Scholar 

  14. 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). https://doi.org/10.1093/glycob/cwab105

    Article  CAS  PubMed  Google Scholar 

  15. Katayama, T., Fujita, K., Yamamoto, K.: Novel bifidobacterial glycosidases acting on sugar chains of mucin glycoproteins. J. Biosci. Bioeng. 99, 457–465 (2005). https://doi.org/10.1263/jbb.99.457

    Article  CAS  PubMed  Google Scholar 

  16. Kitaoka, M., Katayama, T., Yamamoto, K.: Metabolic pathway of human milk oligosaccharides in Bifidobacteria. In: Sonomoto, K., Yokota, A. (eds.) Lactic Acid Bacteria and Bifidobacteria: Current Progress in Advanced Research, pp. 53–65. Caiser Academic Press, Poole (2011)

    Google Scholar 

  17. Johansson, M.E.V., Ambort, D., Pelaseyed, T., Schutte, A., Gustafsson, J.K., Ermund, A., Subramani, D.B., Holmen-Larrson, J.M., Thomsson, K.A., Bergstrom, J.H., van der Post, S., Rodriguez-Pineiro, A.M., Sjovall, H., Backstrom, M., Hansson, G.C.: Composition and functional role of the mucus layers in the intestine. Cell Mol. Life Sci. 68, 3635–3641 (2011). https://doi.org/10.1007/s00018-011-0822-3

    Article  CAS  PubMed  Google Scholar 

  18. Moniaux, N., Escande, F., Porchet, N., Aubert, J.P., Batra, S.K.: Structural organization and classification of the human mucin genes. Front. Biosci. (Landmark Ed) 6, 1192–1206 (2001). https://doi.org/10.2741/moniaux

    Article  Google Scholar 

  19. Tailford, L.E., Crost, E.H., Kavanaugh, D., Juge, N.: Mucin glycan foraging in the human gut microbiome. Front. Genet. 6, 81 (2015). https://doi.org/10.3389/fgene.2015.00081

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Ringot-Destrez, B., Kalach, N., Mihalache, A., Gosset, P., Michalski, J.C., Léonard, R., Robbe-Masselot, C.: How do they stick together? Bacterial adhesins implicated in the binding of bacteria to the human gastrointestinal mucins. Biochem. Soc. Trans. 45, 389–399 (2017). https://doi.org/10.1042/BST20160167

    Article  CAS  PubMed  Google Scholar 

  21. Paone, P., Cani, P.D.: Mucus barrier, mucins and gut microbiota: the expected slimy partners? Gut 69, 2232–2243 (2020). https://doi.org/10.1136/gutjnl-2020-322260

    Article  CAS  PubMed  Google Scholar 

  22. Johansson, M.E., Jakobsson, H.E., Holmén-Larsson, J., Schütte, A., Ermund, A., Rodríguez-Piñeiro, A.M., Arike, L., Wising, C., Svensson, F., Bäckhed, F., Hansson, G.C.: Normalization of host intestinal mucus layers requires long-term microbial colonization. Cell Host Microbe 18, 582–592 (2015). https://doi.org/10.1016/j.chom.2015.10.007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Nordman, H., Davies, J.R., Lindell, G., De Bolos, C., Francisco, R., Carlstedt, I.: Gastric MUC5AC and MUC6 are large oligomeric mucins that differ in size, glycosylation and tissue distribution. Biochem. J. 364, 191–200 (2002). https://doi.org/10.1042/bj3640191

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Lindén, S.K., Florin, T.H.J., McGuckin, M.A., Gay, N.: Mucin dynamics in intestinal bacterial infection. PLoS One 3, e3952 (2008). https://doi.org/10.1371/journal.pone.0003952

  25. Shibahara, H., Higashi, M., Koriyama, C., Yokoyama, S., Kitazono, I., Kurumiya, Y., Narita, M., Kuze, S., Kyokane, T., Mita, S., Arai, T., Kato, T., Yuasa, N., Yamaguchi, R., Kubota, H., Suzuki, H., Baba, S., Rousseau, K., Batra, S. K., Yonezawa, S.: Pathobiological implications of mucin (MUC) expression in the outcome of small bowel cancer. PLoS One 9, e86111 (2014). https://doi.org/10.1371/journal.pone.0086111

  26. Corfield, A.P.: Mucins: a biologically relevant glycan barrier in mucosal protection. Biochim. Biophys. Acta Gen. Subj. 1850, 236–252 (2015). https://doi.org/10.1016/j.bbagen.2014.05.003

    Article  CAS  Google Scholar 

  27. Brockhausen, I., Schachter, H., Stanley, P.: O-GalNAc Glycans. In Varki, A., Cummings, R.D., Esko, J.D., Freeze, H.H., Stanley, P., Bertozzi, C.R., Hart, G.W., Etzler, M.E. (eds.) Essentials of Glycobiology, 2nd Edn., pp. 115–127. Cold Spring Harbor, New York (2009)

  28. Robbe, C., Capon, C., Coddeville, B., Michalski, J.C.: Structural diversity and specific distribution of O-glycans in normal human mucins along the intestinal tract. Biochem. J. 384, 307–316 (2004). https://doi.org/10.1042/BJ20040605

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Kudelka, M.R., Ju, T., Heimburg-Molinaro, J., Cummings, R.D.: Simple sugars to complex disease — Mucin-type O-glycans in cancer. Adv. Cancer Res. 126, 53–135 (2015). https://doi.org/10.1016/bs.acr.2014.11.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Sperandio, B., Fischer, N., Joncquel Chevalier-Curt, M., Rossez, Y., Roux, P., Robbe Masselot, C., Sansonetti, P.J.: Virulent Shigella flexneri affects secretion, expression, and glycosylation of gel-forming mucins in mucus-producing cells. Infect. Immun. 81, 3632–3643 (2013). https://doi.org/10.1128/IAI.00551-13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Zhang, Y., Wang, L., Ocansey, D., Wang, B., Wang, L., Xu, Z.: Mucin-type O-glycans: barrier, microbiota, and immune anchors in inflammatory bowel disease. J. Inflamm. Res. 14, 5939–5953 (2021). https://doi.org/10.2147/JIR.S327609

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Jakobsson, H.E., Rodríguez-Piñeiro, A.M., Schütte, A., Ermund, A., Boysen, P., Bemark, M., Sommer, F., Bäckhed, F., Hansson, G.C., Johansson, M.E.V.: The composition of the gut microbiota shapes the colon mucus barrier. EMBO Rep. 16, 164–177 (2015). https://doi.org/10.15252/embr.201439263

    Article  CAS  PubMed  Google Scholar 

  33. Kim, Y.S., Ho, S.B.: Intestinal goblet cells and mucins in health and disease: recent insights and progress. Curr. Gastroenterol Rep. 12, 319–330 (2010). https://doi.org/10.1007/s11894-010-0131-2

    Article  PubMed  PubMed Central  Google Scholar 

  34. Sommer, F., Bäckhed, F.: The gut microbiota — masters of host development and physiology. Nat. Rev. Microbiol. 11, 227–238 (2013). https://doi.org/10.1038/nrmicro2974

    Article  CAS  PubMed  Google Scholar 

  35. Li, H., Limenitakis, J., Fuhrer, T., Geuking, M.B., Lawson, M.A., Wyss, M., Brugiroux, S., Keller, I., Macpherson, J.A., Rupp, S., Stolp, B., Stein, J.V., Stecher, B., Sauer, U., McCoy, K.D., Macpherson, A.J.: The outer mucus layer hosts a distinct intestinal microbial niche. Nat. Commun. 6, 8292 (2015). https://doi.org/10.1038/ncomms9292

    Article  CAS  PubMed  Google Scholar 

  36. Sommer, F., Adam, N., Johansson, M.E.V., Xia, L., Hansson, G.C., Bäckhed, F.: Altered mucus glycosylation in core 1 O-glycan-deficient mice affects microbiota composition and intestinal architecture. PLoS One 9, e85254 (2014). https://doi.org/10.1371/journal.pone.0085254

  37. Schroeder, B.O.: Fight them or feed them: how the intestinal mucus layer manages the gut microbiota. Gastroenterol. Rep. 7, 3–12 (2019). https://doi.org/10.1093/gastro/goy052

    Article  Google Scholar 

  38. Arike, L., Holmén-Larsson, J., Hansson, G.C.: Intestinal Muc2 mucin O-glycosylation is affected by microbiota and regulated by differential expression of glycosyltranferases. Glycobiology 27, 318–328 (2017). https://doi.org/10.1093/glycob/cww134

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Gagneux, P., Varki, A.: Evolutionary considerations in relating oligosaccharide diversity to biological function. Glycobiology 9, 747–755 (1999). https://doi.org/10.1093/glycob/9.8.747

    Article  CAS  PubMed  Google Scholar 

  40. Tashiro, M., Iwata, A., Yamauchi, M., Shimizu, K., Okada, A., Ishiguro, N., Inoshima, Y.: The N-terminal region of serum amyloid A3 protein activates NF-κB and up-regulates MUC2 mucin mRNA expression in mouse colonic epithelial cells. PLoS One 12, e0181796 (2017). https://doi.org/10.1371/journal.pone.0181796

  41. Marcobal, A., Southwick, A.M., Earle, K.A., Sonnenburg, J.L.: A refined palate: bacterial consumption of host glycans in the gut. Glycobiology 23, 1038–1046 (2013). https://doi.org/10.1093/glycob/cwt040

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. González-Morelo, K.J., Vega-Sagardía, M., Garrido, D.: Molecular insights into O-linked glycan utilization by gut microbes. Front. Microbiol. 11, 591568 (2020). https://doi.org/10.3389/fmicb.2020.591568

  43. Macchione, I.G., Lopetuso, L.R., Ianiro, G., Napoli, M., Gibiino, G., Rizzatti, G., Petito, V., Gasbarrini, A., Scaldaferri, F.: Akkermansia muciniphila: key player in metabolic and gastrointestinal disorders. Eur. Rev. Med. Pharmacol. Sci. 23, 8075–8083 (2019). https://doi.org/10.26355/eurrev_201909_19024

    Article  CAS  PubMed  Google Scholar 

  44. Ndeh, D., Gilbert, H.J.: Biochemistry of complex glycan depolymerisation by the human gut microbiota. FEMS Microbiol. Rev. 42, 146–164 (2018). https://doi.org/10.1093/femsre/fuy002

    Article  CAS  PubMed  Google Scholar 

  45. Etzold, S., Juge, N.: Structural insights into bacterial recognition of intestinal mucins. Curr. Opin. Struct. Biol. 28, 23–31 (2014). https://doi.org/10.1016/j.sbi.2014.07.002

    Article  CAS  PubMed  Google Scholar 

  46. Kansal, R., Rasko, D.A., Sahl, J.W., Munson, G.P., Roy, K., Luo, Q., Sheikh, A., Kuhne, K.J., Fleckenstein, J.M.: Transcriptional modulation of enterotoxigenic Escherichia coli virulence genes in response to epithelial cell interactions. Infect. Immun. 81, 259–270 (2013). https://doi.org/10.1128/IAI.00919-12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Joncquel Chevalier Curt, M., Lecointe, K., Mihalache, A., Rossez, Y., Gosset, P., Léonard, R., Robbe-Masselot, C.: Alteration or adaptation, the two roads for human gastric mucin glycosylation infected by Helicobacter pylori. Glycobiology 25, 617–631 (2015). https://doi.org/10.1093/glycob/cwv004

  48. Dhanani, A.S., Bagchi, T.: The expression of adhesin EF-Tu in response to mucin and its role in Lactobacillus adhesion and competitive inhibition of enteropathogens to mucin. J. Appl. Microbiol. 115, 546–554 (2013). https://doi.org/10.1111/jam.12249

    Article  CAS  PubMed  Google Scholar 

  49. Etzold, S., Kober, O.I., Mackenzie, D.A., Tailford, L.E., Gunning, A.P., Walshaw, J., Hemming, A.M., Juge, N.: Structural basis for adaptation of lactobacilli to gastrointestinal mucus. Environ. Microbiol. 16, 888–903 (2014). https://doi.org/10.1111/1462-2920.12377

    Article  CAS  PubMed  Google Scholar 

  50. Koropatkin, N., Martens, E.C., Gordon, J.I., Smith, T.J.: The structure of a SusD homologue, BT1043, involved in mucin O-glycan utilization in a prominent human gut symbiont. Biochemistry 48, 1532–1542 (2009). https://doi.org/10.1021/bi801942a

    Article  CAS  PubMed  Google Scholar 

  51. Garrido, D., Kim, J.H., German, J.B., Raybould, H.E., Mills, D.A., Uversky, V.: Oligosaccharide binding proteins from Bifidobacterium longum subsp. infantis reveal a preference for host glycans. PLoS One 6, e17315 (2011). https://doi.org/10.1371/journal.pone.0017315

  52. Tremaroli, V., Backhed, F.: Functional interactions between the gut microbiota and host metabolism. Nature 489, 242–249 (2012). https://doi.org/10.1038/nature11552

    Article  CAS  PubMed  Google Scholar 

  53. 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). https://doi.org/10.1016/j.bpg.2013.03.001

    Article  CAS  PubMed  Google Scholar 

  54. Martens, E.C., Chiang, H.C., Gordon, J.I.: Mucosal glycan foraging enhances fitness and transmission of a saccharolytic human gut bacterial symbiont. Cell Host Microbe. 4, 447–457 (2008). https://doi.org/10.1016/j.chom.2008.09.007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Yamada, T., Hino, S., Iijima, H., Genda, T., Aoki, R., Nagata, R., Han, K.-H., Hirota, M., Kinashi, Y., Oguchi, H., Suda, W., Furusawa, Y., Fujimura, Y., Kunisawa, J., Hattori, M., Fukushima, M., Morita, T., Hase, K.: Mucin O-glycans facilitate symbiosynthesis to maintain gut immune homeostasis. EBioMedicine 48, 513–525 (2019). https://doi.org/10.1016/j.ebiom.2019.09.008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Rajilić-Stojanović, M., de Vos, W.M.: The first 1000 cultured species of the human gastrointestinal microbiota. FEMS Microbiol. Rev. 38, 996–1047 (2014). https://doi.org/10.1111/1574-6976.12075

    Article  CAS  PubMed  Google Scholar 

  57. Wexler, A.G., Goodman, A.L.: An insider’s perspective: Bacteroides as a window into the microbiome. Nat. Microbiol. 25, 17026 (2017). https://doi.org/10.1038/nmicrobiol.2017.26

    Article  CAS  Google Scholar 

  58. Brown, H.A., Koropatkin, N.M.: Host glycan utilization within the Bacteroidetes Sus-like paradigm. Glycobiology 31, 697–706 (2021). https://doi.org/10.1093/glycob/cwaa054

    Article  CAS  PubMed  Google Scholar 

  59. Cao, Y., Rocha, E.R., Smith, C.J.: Efficient utilization of complex N-linked glycans is a selective advantage for Bacteroides fragilis in extraintestinal infections. Proc. Natl. Acad. Sci. U.S.A. 111, 12901–12906 (2014). https://doi.org/10.1073/pnas.1407344111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Lee, S.M., Donaldson, G.P., Mikulski, Z., Boyajian, S., Ley, K., Mazmanian, S.K.: Bacterial colonization factors control specificity and stability of the gut microbiota. Nature 501, 426–429 (2013). https://doi.org/10.1038/nature12447

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Cockburn, D.W., Koropatkin, N.M.: Polysaccharide degradation by the intestinal microbiota and its influence on human health and disease. J. Mol. Biol. 428, 3230–3252 (2016). https://doi.org/10.1016/j.jmb.2016.06.021

    Article  CAS  PubMed  Google Scholar 

  62. Pluvinage, B., Massel, P.M., Burak, K., Boraston, A.B.: Structural and functional analysis of four family 84 glycoside hydrolases from the opportunistic pathogen Clostridium perfringens. Glycobiology 30, 49–57 (2019). https://doi.org/10.1093/glycob/cwz069

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Roberts, G., Tarelli, E., Homer, K.A., Philpott-Howard, J., Beighton, D.: Production of an endo-β-N-acetylglucosaminidase activity mediates growth of Enterococcus faecalis on a high-mannose-type glycoprotein. J. Bacteriol. 182, 882–890 (2000). https://doi.org/10.1128/JB.182.4.882-890.2000

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Etzold, S., Kober, O.I., Mackenzie, D.A., Tailford, L.E., Gunning, A.P., Walshaw, J., Hemmings, A.M., Juge, N.: Structural basis for adaptation of lactobacilli to gastrointestinal mucus. Environ. Microbiol. 16, 888–903 (2014). https://doi.org/10.1111/1462-2920.12377

    Article  CAS  PubMed  Google Scholar 

  65. Buck, B.L., Altermann, E., Svingerud, T., Klaenhammer, T.R.: Functional analysis of putative adhesion factors in Lactobacillus acidophilus NCFM. Appl. Environ. Microbiol. 71, 8344–8351 (2005). https://doi.org/10.1128/AEM.71.12.8344-8351.2005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Rojas, M., Ascencio, F., Conway, P.L.: Purification and characterization of a surface protein from Lactobacillus fermentum 104R that binds to porcine small intestinal mucus and gastric mucin. Appl. Environ. Microbiol. 68, 2330–2336 (2002). https://doi.org/10.1128/AEM.68.5.2330-2336.2002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Macías-Rodríguez, M.E., Zagorec, M., Ascencio, F., Vázquez-Juárez, R., Rojas, M.: Lactobacillus fermentum BCS87 expresses mucus- and mucin-binding proteins on the cell surface. J. Appl. Microbiol. 107, 1866–1874 (2009). https://doi.org/10.1111/j.1365-2672.2009.04368

    Article  PubMed  Google Scholar 

  68. Png, C.W., Linden, S.K., Gilshenan, K.S., Zoetendal, E.G., McSweeney, C.S., Sly, L.I., McGuckin, M.A., Florin, T.H.: Mucolytic bacteria with increased prevalence in IBD mucosa augment in vitro utilization of mucin by other bacteria. Am. J. Gastroenterol. 105, 2420–2428 (2010). https://doi.org/10.1038/ajg.2010.281

    Article  CAS  PubMed  Google Scholar 

  69. Katoh, T., Maeshibu, T., Kikkawa, K., Gotoh, A., Tomabechi, Y., Nakamura, M., Liao, W.H., Yamaguchi, M., Ashida, H., Yamamoto, K., Katayama, T.: Identification and characterization of a sulfoglycosidase from Bifidobacterium bifidum implicated in mucin glycan utilization. Biosci. Biotechnol. Biochem. 81, 2018–2027 (2017). https://doi.org/10.1080/09168451.2017.1361810

    Article  CAS  PubMed  Google Scholar 

  70. Yamamoto, K.: Biological Analysis of the Microbial Metabolism of Hetero-Oligosaccharides in Application to Glycotechnology. Biosci. Biotechnol. Biochem. 76, 1815–1827 (2012). https://doi.org/10.1271/bbb.120401J

    Article  CAS  PubMed  Google Scholar 

  71. Sela, D.A., Chapman, J., Adeuya, A., Kim, J.H., Chen, F., Whitehead, T.R., Lapidus, A., Rokhsar, D.S., Lebrilla, C.B., German, J.B., Price, N.P., Richardson, P.M., Mills, D.A.: The genome sequence of Bifidobacterium longum subsp infantis reveals adaptations for milk utilization within the infant microbiome. Proc. Natl. Acad. Sci. USA 105, 18964–18969 (2008). https://doi.org/10.1073/pnas.0809584105

    Article  PubMed  PubMed Central  Google Scholar 

  72. Zúñiga, M., Monedero, V., Yebra, M.J.: Utilization of host-derived glycans by intestinal Lactobacillus and Bifidobacterium species. Front. Microbiol. 9, 1917 (2018). https://doi.org/10.3389/fmicb.2018.01917

    Article  PubMed  PubMed Central  Google Scholar 

  73. Katoh, T., Ojima, M.N., Sakanaka, M., Ashida, H., Gotoh, A., Katayama, T.: Enzymatic adaptation of Bifidobacterium bifidum to host glycans, viewed from glycoside hydrolyases and carbohydrate-binding modules. Microorganisms 8, 481 (2020). https://doi.org/10.3390/microorganisms8040481

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. 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). https://doi.org/10.1099/ijs.0.02873-0

  75. Lopez-Siles, M., Enrich-Capó, N., Aldeguer, X., Sabat-Mir, M., Duncan, S.H., Garcia-Gil, L.J., Martinez-Medina, M.: Alterations in the abundance and co-occurrence of Akkermansia muciniphila and Faecalibacterium prausnitzii in the colonic mucosa of inflammatory bowel disease subjects. Front. Cell. Infect. Microbiol. 8, 281 (2018). https://doi.org/10.3389/fcimb.2018.00281

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Cani, P.D., de Vos, W.M.: Next-generation beneficial microbes: the case of Akkermansia muciniphila. Front. Microbiol. 8, 1765 (2017). https://doi.org/10.3389/fmicb.2017.01765

    Article  PubMed  PubMed Central  Google Scholar 

  77. Depommier, C., Everard, A., Druart, C., Plovier, H., Van Hul, M., Vieira-Silva, S., Falony, G., Raes, J., Maiter, D., Delzenne, N.M., de Barsy, M., Loumaye, A., Hermans, M.P., Thissen, J.P., de Vos, W.M., Cani, P.D.: Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study. Nat. Med. 25, 1096–1103 (2019). https://doi.org/10.1038/s41591-019-0495-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Earley, H., Lennon, G., Balfe, Á., Coffey, J.C., Winter, D.C., O’Connell, P.R.: The abundance of Akkermansia muciniphila and its relationship with sulphated colonic mucins in health and ulcerative colitis. Sci. Rep. 9, 15683 (2019). https://doi.org/10.1038/s41598-019-51878-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Belzer, C., Chia, L.W., Aalvink, S., Chamlagain, B., Piironen, V., Knol, J., de Vos, W.M.: Microbial metabolic networks at the mucus layer lead to diet-independent butyrate and vitamin B12 production by intestinal symbionts. MBio 8, e00770-17 (2017). https://doi.org/10.1128/mBio.00770-17

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Rawat, P.S., Seyed Hameed, A.S., Meng, X., Liu, W.: Utilization of glycosaminoglycans by the human gut microbiota: participating bacteria and their enzymatic machineries. Gut Microbes 14, 2068367 (2022). https://doi.org/10.1080/19490976.2022.2068367

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Moran, A.P., Gupta, A., Joshi, L.: Sweet-talk: role of host glycosylation in bacterial pathogenesis of the gastrointestinal tract. Gut 60, 1412–1425 (2011). https://doi.org/10.1136/gut.2010.212704

    Article  CAS  PubMed  Google Scholar 

  82. Belmiro, C.L., Souza, H.S., Elia, C.C., Castelo-Branco, M.T., Silva, F.R., Machado, R.L., Pavão, M.S.: Biochemical and immunohistochemical analysis of glycosaminoglycans in inflamed and non-inflamed intestinal mucosa of patients with Crohn’s disease. Int. J. Colorectal Dis. 20, 295–304 (2005). https://doi.org/10.1007/s00384-004-0677-2

    Article  PubMed  Google Scholar 

  83. Cheng, Q., Salyers, A.A.: Use of suppressor analysis to find genes involved in the colonization deficiency of a Bacteroides thetaiotaomicron mutant unable to grow on the host-derived mucopolysaccharides chondroitin sulfate and heparin. Appl. Environ. Microbiol. 61(734–740), 1995 (1995). https://doi.org/10.1128/aem.61.2.734-740

    Article  Google Scholar 

  84. Salyers, A.A., O’Brien, M.: Cellular location of enzymes involved in chondroitin sulfate breakdown by Bacteroides thetaiotaomicron. J. Bacteriol. 143, 772–780 (1980). https://doi.org/10.1128/jb.143.2.772-780.1980

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Ndeh, D., Baslé, A., Strahl, H., Yates, E.A., McClurgg, U.L., Henrissat, B., Terrapon, N., Cartmell, A.: Metabolism of multiple glycosaminoglycans by Bacteroides thetaiotaomicron is orchestrated by a versatile core genetic locus. Nat. Commun. 11, 646 (2020). https://doi.org/10.1038/s41467-020-14509-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Cartmell, A., Lowe, E.C., Baslé, A., Firbank, S.J., Ndeh, D.A., Murray, H., Terrapon, N., Lombard, V., Henrissat, B., Turnbull, J.E., Czjzek, M., Gilbert, H.J., Bolam, D.N.: How members of the human gut microbiota overcome the sulfation problem posed by glycosaminoglycans. Proc. Natl. Acad. Sci. U.S.A. 114, 7037–7042 (2017). https://doi.org/10.1073/pnas.1704367114

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Salyers, A.A., West, S.E., Vercellotti, J.R/, Wilkins, T.D.: Fermentation of mucins and plant polysaccharides by anaerobic bacteria from the human colon. Appl. Environ. Microbiol. 34, 529–533 (1977). https://doi.org/10.1128/aem.34.5.529-533.1977

  88. Kawai, K., Kamochi, R., Oiki, S., Murata, K., Hashimoto, W.: Probiotics in human gut microbiota can degrade host glycosaminoglycans. Sci Rep. 8, 10674 (2018). https://doi.org/10.1038/s41598-018-28886-w

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Lee, B., Lee, J.H., Lee, H.S., Bae, E.A., Huh, C.S., Ahn, Y.T., Kim, D.H.: Glycosaminoglycan degradation-inhibitory lactic acid bacteria ameliorate 2,4,6-trinitrobenzenesulfonic acid-induced colitis in mice. J. Microbiol. Biotechnol. 19, 616–621 (2009). https://doi.org/10.4014/jmb.0808.479

    Article  CAS  PubMed  Google Scholar 

  90. Bell, A., Juge, N.: Mucosal glycan degradation of the host by the gut microbiota. Glycobiology 31, 691–696 (2021). https://doi.org/10.1093/glycob/cwaa097

    Article  CAS  PubMed  Google Scholar 

  91. Belzer, C.: Nutritional strategies for mucosal health: the interplay between microbes and mucin glycans. Trends Microbiol. 30, 13–21 (2022). https://doi.org/10.1016/j.tim.2021.06.003

    Article  CAS  PubMed  Google Scholar 

  92. Derrien, M., van Passel, M.W., van de Bovenkamp, J.H., Schipper, R.G., de Vos, W.M., Dekker, J.: Mucin-bacterial interactions in the human oral cavity and digestive tract. Gut Microbes 1, 254–268 (2010). https://doi.org/10.4161/gmic.1.4.12778

    Article  PubMed  PubMed Central  Google Scholar 

  93. Turroni, F., Milani, C., Duranti, S., Mahony, J., van Sinderen, D., Ventura, M.: Glycan utilization and cross-feeding activities by Bifidobacteria. Trends Microbiol. 26, 339–350 (2018). https://doi.org/10.1016/j.tim.2017.10.001

    Article  CAS  PubMed  Google Scholar 

  94. Crouch, L.I., Liberato, M.V., Urbanowicz, P.A., Baslé, A., Lamb, C.A., Stewart, C.J., Cooke, K., Doona, M., Needham, S., Brady, R.R., Berrington, J.E., Madunic, K., Wuhrer, M., Chater, P., Pearson, J.P., Glowacki, R., Martens, E.C., Zhang, F., Linhardt, R.J., Spencer, D.I.R., Bolam, D.N.: Prominent members of the human gut microbiota express endo-acting O-glycanases to initiate mucin breakdown. Nat. Commun. 11, 4017 (2020). https://doi.org/10.1038/s41467-020-17847-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Glover, J.S., Ticer, T.D., Engevik, M.A.: Characterizing the mucin-degrading capacity of the human gut microbiota. Sci. Rep. 12, 8456 (2022). https://doi.org/10.1038/s41598-022-11819-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Kuwahara, T., Yamashita, A., Hirakawa, H., Nakayama, H., Toh, H., Okada, N., Kuhara, S., Hattori, M., Hayashi, T., Ohnishi, Y.: Genomic analysis of Bacteroides fragilis reveals extensive DNA inversions regulating cell surface adaptation. Proc. Natl. Acad. Sci. USA 101, 14919–14924 (2004). https://doi.org/10.1073/pnas.0404172101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Martens, E.C., Chiang, H.C., Gordon, J.I.: Mucosal glycan foraging enhances fitness and transmission of a saccharolytic human gut bacterial symbiont. Cell Host Microbe 4, 447–457 (2008). https://doi.org/10.1016/j.chom.2008.09.007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Luis, A.S., Briggs, J., Zhang, X., Farnell, B., Ndeh, D., Labourel, A., Baslé, A., Cartmell, A., Terrapon, N., Stott, K., Lowe, E.C., McLean, R., Shearer, K., Schückel, J., Venditto, I., Ralet, M.C., Henrissat, B., Martens, E.C., Mosimann, S.C., Abbott, D.W., Gilbert, H.J.: Dietary pectic glycans are degraded by coordinated enzyme pathways in human colonic Bacteroides. Nat. Microbiol. 3, 210–219 (2018). https://doi.org/10.1038/s41564-017-0079-1

    Article  CAS  PubMed  Google Scholar 

  99. Marcobal, A., Barboza, M., Sonnenburg, E.D., Pudlo, N., Martens, E.C., Desai, P., Lebrilla, C.B., Weimer, B.C., Mills, D.A., German, J.B., Sonnenburg, J.L.: Bacteroides in the infant gut consume milk oligosaccharides via mucus-utilization pathways. Cell Host Microbe 10, 507–514 (2011). https://doi.org/10.1016/j.chom.2011.10.007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Pudlo, N.A., Urs, K., Kumar, S.S., German, J.B., Mills, D.A., Martens, E. C.: Symbiotic human gut bacteria with variable metabolic priorities for host mucosal glycans. mBio 6, e01282–15 (2015). https://doi.org/10.1128/mBio.01282-15

  101. Chung, L., Orberg, E.T., Geis, A.L., Chan, J.L., Fu, K., DeStefano Shields, C.E., Dejea, C.M., Fathi, P., Chen, J., Finard, B.B., Tam, A.J., McAllister, F., Fan, H., Wu, X., Ganguly, S., Lebid, A., Metz, P., Van Meerbeke, S.W., Huso, D.L., Wick, E.C., Pardoll, D.M., Wan, F., Wu, S., Sears, C.L., Housseau, F.: Bacteroides fragilis toxin coordinates a pro-carcinogenic inflammatory cascade via targeting of colonic epithelial cells. Cell Host Microbe 23, 203–214 (2018). https://doi.org/10.1016/j.chom.2018.02.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Garron, M.-L., Cygler, M.: Structural and mechanistic classification of uronic acid-containing polysaccharide lyases. Glycobiology 20, 1547–1573 (2010). https://doi.org/10.1093/glycob/cwq122

    Article  CAS  PubMed  Google Scholar 

  103. Cartmell, A., Lowe, E.C., Baslé, A., Firbank, S.J., Ndeh, D.A., Murray, H., Terrapon, N., Lombard, V., Henrissat, B., Turnbull, J.E., Czjzek, M., Gilbert, H.J., Bolam, D.N.: How members of the human gut microbiota overcome the sulfation problem posed by glycosaminoglycans. Proc. Natl. Acad. Sci. USA 114, 7037–7042 (2017). https://doi.org/10.1073/pnas.1704367114

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Ottman, N., Huuskonen, L., Reunanen, J., Boeren, S., Klievink, J., Smidt, H., Belzer, C., de Vos, W.M.: Characterization of outer membrane proteome of Akkermansia muciniphila reveals sets of novel proteins exposed to the human intestine. Front. Microbiol. 7, 1157 (2016). https://doi.org/10.3389/fmicb.2016.01157

    Article  PubMed  PubMed Central  Google Scholar 

  105. Shin, J., Noh, J.R., Chang, D.H., Kim, Y.H., Kim, M.H., Lee, E.S., Cho, S., Ku, B.J., Rhee, M.S., Kim, B.C., Lee, C.H., Cho, B.K.: Elucidation of Akkermansia muciniphila probiotic traits driven by mucin depletion. Front. Microbiol. 10, 1137 (2019). https://doi.org/10.3389/fmicb.2019.01137

    Article  PubMed  PubMed Central  Google Scholar 

  106. Meng, X., Wang, W., Lan, T., Yang, W., Yu, D., Fang, X., Wu, H.: A purified aspartic protease from Akkermansia Muciniphila plays an important role in degrading Muc2. Int. J. Mol. Sci. 21, 72 (2019). https://doi.org/10.3390/ijms21010072

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. 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). https://doi.org/10.1016/j.ijbiomac.2020.01.246

    Article  CAS  PubMed  Google Scholar 

  108. Bell, A., Brunt, J., Crost, E., Vaux, L., Nepravishta, R., Owen, C.D., Latousakis, D., Xiao, A., Li, W., Chen, X., Walsh, M.A., Claesen, J., Angulo, J., Thomas, G.H., Juge, N.: Elucidation of a sialic acid metabolism pathway in mucus-foraging Ruminococcus gnavus unravels mechanisms of bacterial adaptation to the gut. Nat. Microbiol. 4, 2393–2404 (2019). https://doi.org/10.1038/s41564-019-0590-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Tailford, L.E., Owen, C.D., Walshaw, J., Crost, E.H., Hardy-Goddard, J., Le Gall, G., de Vos, W.M., Taylor, G.L., Juge, N.: Discovery of intramolecular trans-sialidases in human gut microbiota suggests novel mechanisms of mucosal adaptation. Nat. Commun. 6, 1–12 (2015). https://doi.org/10.1038/ncomms8624

    Article  CAS  Google Scholar 

  110. Turronia, F., Bottacinia, F., Foronia, E., Mulderd, I., Kime, J.-H., Zomerb, A., Sánchezf, B., Bidossig, A., Ferrarinih, A., Giubellinia, A., Delledonneh, M., Henrissati, B., Coutinhoi, P., Oggionig, M., Fitzgerald, G.F., Millse, D., Margollesf, A., Kellyd, D., van Sinderen, D., Ventura, M.: Genome analysis of Bifidobacterium bifidum PRL2010 reveals metabolic pathways for host-derived glycan foraging. Proc. Natl. Acad. Sci. USA 107, 19514–19519 (2010). https://doi.org/10.1073/pnas.1011100107

    Article  Google Scholar 

  111. Abe, F., Muto, M., Yaeshima, T., Iwatsuki, K., Aihara, H., Ohashi, Y., Fujisawa, T.: Safety evaluation of probiotic bifidobacteria by analysis of mucin degradation activity and translocation ability. Anaerobe 16, 131–136 (2010). https://doi.org/10.1016/j.anaerobe.2009.07.006

    Article  CAS  PubMed  Google Scholar 

  112. Ruas-Madiedo, P., Gueimonde, M., Fernandez-Garcia, M., De Los Reyes-Gavilan, C.G., Margolles, A.: Mucin degradation by Bifidobacterium strains isolated from the human intestinal microbiota. Appl. Environ. Microbiol. 74, 1936–1940 (2008). https://doi.org/10.1128/AEM.02509-07

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Katayama, T., Sakuma, A., Kimura, T., Makimura, Y., Hiratake, J., Sakata, K., Yamanoi, T., Kumagai, H., Yamamoto, K.: Molecular cloning and characterization of Bifidobacterium bifidum 1,2-α-L-fucosidase (AfcA), a novel inverting glycosidase (glycoside hydrolase family 95). J. Bacteriol. 186, 4885–4893 (2004). https://doi.org/10.1128/jb.186.15.4885-4893.2004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Ashida, H., Miyake, A., Kiyohara, M., Wada, J., Yoshida, E., Kumagai, H., Katayama, T., Yamamoto, K.: Two distinct alpha-L-fucosidases from Bifidobacterium bifidum are essential for the utilization of fucosylated milk oligosaccharides and glycoconjugates. Glycobiology 19, 1010–1017 (2009). https://doi.org/10.1093/glycob/cwp082

    Article  CAS  PubMed  Google Scholar 

  115. Fujita, K., Oura, F., Nagamine, N., Katayama, T., Hiratake, J., Sakata, K., Kumagai, H., Yamamoto, K.: Identification and molecular cloning of a novel glycoside hydrolase family of core 1 type O-glycan-specific endo-alpha-N-acetylgalactosaminidase from Bifidobacterium longum. J. Biol. Chem. 280, 37415–37422 (2005). https://doi.org/10.1074/jbc.M506874200

    Article  CAS  PubMed  Google Scholar 

  116. Koutsioulis, D., Landry, D., Guthrie, E.P.: Novel endo-alpha-N-acetylgalactosaminidases with broader substrate specificity. Glycobiology 18, 799–805 (2008). https://doi.org/10.1093/glycob/cwn069

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Kiyohara, M., Nakatomi, T., Kurihara, S., Fushinobu, S., Suzuki, H., Tanaka, T., Shoda, S.-I., Kitaoka, M., Katayama, T., Yamamoto, K., Ashida, H.: α-N-Acetylgalactosaminidase from infant-associated Bifidobacteria belonging to novel glycoside hydrolase family 129 is implicated in alternative mucin degradation pathway. J. Biol. Chem. 287, 693–700 (2012). https://doi.org/10.1074/jbc.M111.277384

    Article  CAS  PubMed  Google Scholar 

  118. Miwa, M., Horimoto, T., Kiyohara, M., Katayama, T., Kitaoka, M., Ashida, H., Yamamoto, K.: Cooperation of β-galactosidase and β-N-acetylhexosaminidase from bifidobacteria in assimilation of human milk oligosaccharides with type 2 structure. Glycobiology 20, 1402–1409 (2010). https://doi.org/10.1093/glycob/cwq101

    Article  CAS  PubMed  Google Scholar 

  119. Yoshida, E., Sakurama, H., Kiyohara, M., Nakajima, M., Kitaoka, M., Ashida, H., Hirose, J., Katayama, T., Kumagai, H.: Bifidobacterium longum subsp. infantis uses two different β-galactosidases for selectively degrading type-1 and type-2 human milk oligosaccharides. Glycobiology 22, 361–368 (2012). https://doi.org/10.1093/glycob/cwr116

  120. Wada, J., Ando, T., Kiyohara, M., Ashida, H., Kitaoka, M., Yamaguchi, M., Kumagai, H., Katayama, T., Yamamoto, K.: Bifidobacterium bifidum lacto-N-biosidase, a critical enzyme for the degradation of human milk oligosaccharides with a type 1 structure. Appl. Environ. Microbiol. 74, 3996–4004 (2008). https://doi.org/10.1128/AEM.00149-08

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Suzuki, R., Wada, J., Katayama, T., Fushinobu, S., Wakagi, T., Shoun, H., Sugimoto, H., Tanaka, A., Kumagai, H., Ashida, H., Kitaoka, M., Yamamoto, K.: Structural and thermodynamic analyses of solute-binding protein from Bifidobacterium longum specific for core 1 disaccharide and lacto-N-biose I. J. Biol. Chem. 283, 13165–13173 (2008). https://doi.org/10.1074/jbc.M709777200

    Article  CAS  PubMed  Google Scholar 

  122. Yoshida, E., Sakurama, H., Kiyohara, M., Nakajima, M., Kitaoka, M., Ashida, H., Hirose, J., Katayama, T., Yamamoto, K., Kumagai, H.: Bifidobacterium longum subsp. infantis uses two different β-galactosidases for selectively degrading type-1 and type-2 human milk oligosaccharides. Glycobiology 22, 361–368 (2012). https://doi.org/10.1093/glycob/cwr116

  123. Rho, J.H., Wright, D.P., Christie, D.L., Clinch, K., Furneaux, R.H., Roberton, A.M.: A novel mechanism for desulfation of mucin: identification and cloning of a mucin-desulfating glycosidase (sulfoglycosidase) from Prevotella strain RS2. J. Bacteriol. 187, 1543–1551 (2005). https://doi.org/10.1128/JB.187.5.1543-1551.2005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Benjdia, A., Martens, E.C., Gordon, J.I., Berteau, O.: Sulfatases and a radical S-adenosyl-L-methionine (AdoMet) enzyme are key for mucosal foraging and fitness of the prominent human gut symbiont. Bacteroides thetaiotaomicron. J. Biol. Chem. 286, 25973–25982 (2011). https://doi.org/10.1074/jbc.M111.228841

    Article  CAS  PubMed  Google Scholar 

  125. Luis, A.S., Jin, C., Pereira, G.V., Glowacki, R.W.P., Gugel, S.R., Singh, S., Byrne, D.P., Pudlo, N.A., London, J.A., Baslé, A., Reihill, M., Oscarson, S., Eyers, P.A., Czjzek, M., Michel, G., Barbeyron, T., Yates, E.A., Hansson, G.C., Karlsson, N.G., Cartmell, A., Martens, E.C.: A single sulfatase is required to access colonic mucin by a gut bacterium. Nature 598, 332–337 (2021). https://doi.org/10.1038/s41586-021-03967-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Birchenough, G., Schroeder, B.O., Bäckhed, F., Hansson, G.C.: Dietary destabilisation of the balance between the microbiota and the colonic mucus barrier. Gut Microbes 10, 246–250 (2019). https://doi.org/10.1080/19490976.2018.1513765

    Article  CAS  PubMed  Google Scholar 

  127. Johansson, M.E., Larsson, J.M., Hansson, G.C.: 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. USA 108(Suppl 1), 4659–4665 (2011). https://doi.org/10.1073/pnas.1006451107

    Article  PubMed  Google Scholar 

  128. Birchenough, G.M., Johansson, M.E., Gustafsson, J.K., Bergström, J.H., Hansson, G.C.: New developments in goblet cell mucus secretion and function. Mucosal Immunol. 8, 712–719 (2015). https://doi.org/10.1038/mi.2015.32

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Van der Sluis, M., De Koning, B.A., De Bruijn, A.C., Velcich, A., Meijerink, J.P., Van Goudoever, J.B., Büller, H.A., Dekker, J., Van Seuningen, I., Renes, I.B., Einerhand, A.W.: Muc2-deficient mice spontaneously develop colitis, indicating that MUC2 is critical for colonic protection. Gastroenterology 131, 117–129 (2006). https://doi.org/10.1053/j.gastro.2006.04.020

    Article  CAS  PubMed  Google Scholar 

  130. Larsson, J.M., Karlsson, H., Crespo, J.G., Johansson, M.E., Eklund, L., Sjövall, H., Hansson, G.C.: Altered O-glycosylation profile of MUC2 mucin occurs in active ulcerative colitis and is associated with increased inflammation. Inflamm. Bowel Dis. 17, 2299–2307 (2011). https://doi.org/10.1002/ibd.21625

    Article  PubMed  Google Scholar 

  131. Bergstrom, K., Fu, J., Johansson, M.E., Liu, X., Gao, N., Wu, Q., Song, J., McDaniel, J.M., McGee, S., Chen, W., Braun, J., Hansson, G.C., Xia, L.: Core 1- and 3-derived O-glycans collectively maintain the colonic mucus barrier and protect against spontaneous colitis in mice. Mucosal Immunol. 10, 91–103 (2017). https://doi.org/10.1038/mi.2016.45

    Article  CAS  PubMed  Google Scholar 

  132. Cornick, S., Tawiah, A., Chadee, K.: Roles and regulation of the mucus barrier in the gut. Tissue Barriers 3, e982426 (2015). https://doi.org/10.4161/21688370.2014.982426

  133. Schultsz, C., Van Den Berg, F.M., Ten Kate, F.W., Tytgat, G.N., Dankert, J.: The intestinal mucus layer from patients with inflammatory bowel disease harbors high numbers of bacteria compared with controls. Gastroenterology 117, 1089–1097 (1999). https://doi.org/10.1016/S0016-5085(99)70

    Article  CAS  PubMed  Google Scholar 

  134. Linskens, R.K., Huijsdens, X.W., Savelkoul, P.H., Vandenbroucke-Grauls, C.M., Meuwissen, S.G.: The bacterial flora in inflammatory bowel disease: current insights in pathogenesis and the influence of antibiotics and probiotics. Scand. J. Gastroenterol. Suppl. 234, 29–40 (2001). https://doi.org/10.1080/003655201753265082

    Article  Google Scholar 

  135. Willing, B.P., Dicksved, J., Halfvarson, J., Andersson, A.F., Lucio, M., Zheng, Z., Järnerot, G., Tysk, C., Jansson, J.K., Engstrand, L.: A pyrosequencing study in twins shows that gastrointestinal microbial profiles vary with inflammatory bowel disease phenotypes. Gastroenterology. 139, 1844-1854.e1 (2010). https://doi.org/10.1053/j.gastro.2010.08.049

    Article  PubMed  Google Scholar 

  136. Prindiville, T., Cantrell, M., Wilson, K.H.: Ribosomal DNA sequence analysis of mucosa-associated bacteria in Crohn’s disease. Inflamm. Bowel Dis. 10, 824–833 (2004). https://doi.org/10.1097/00054725-200411000-00017

    Article  PubMed  Google Scholar 

  137. Ganesh, B.P., Klopfleisch, R., Loh, G., Blaut, M.: Commensal Akkermansia muciniphila exacerbates gut inflammation in Salmonella Typhimurium-infected gnotobiotic mice. PLoS One 8, e74963 (2013). https://doi.org/10.1371/journal.pone.0074963

  138. Hansen, C.H., Krych, L., Nielsen, D.S., Vogensen, F.K., Hansen, L.H., Sorensen, S.J., Buschard, K., Hansen, A.K.: Early life treatment with vancomycin propagates Akkermansia muciniphila and reduces diabetes incidence in the NOD mouse. Diabetologia 55, 2285–2294 (2012). https://doi.org/10.1007/s00125-012-2564-7

    Article  CAS  PubMed  Google Scholar 

  139. Wang, L., Christophersen, C.T., Sorich, M.J., Gerber, J.P., Angley, M.T., Conlon, M.A.: Low relative abundances of the mucolytic bacterium Akkermansia muciniphila and Bifidobacterium spp. in feces of children with autism. Appl. Environ. Microbiol. 77, 6718–6721 (2011). https://doi.org/10.1128/AEM.05212-11

  140. Ellekilde, M., Krych, L., Hansen, C.H., Hufeldt, M.R., Dahl, K., Hansen, L.H., Sørensen, S.J., Vogensen, F.K., Nielsen, D.S., Hansen, A.K.: Characterization of the gut microbiota in leptin deficient obese mice - Correlation to inflammatory and diabetic parameters. Res. Vet. Sci. 96, 241–250 (2014). https://doi.org/10.1016/j.rvsc.2014.01.007

    Article  CAS  PubMed  Google Scholar 

  141. Zhang, J., Ni, Y., Qian, L., Fang, Q., Zheng, T., Zhang, M., Gao, Q., Zhang, Y., Ni, J., Hou, X., Bao, Y., Kovatcheva-Datchary, P., Xu, A., Li, H., Panagiotou, G., Jia, W.: Decreased abundance of Akkermansia muciniphila leads to the impairment of insulin secretion and glucose homeostasis in lean type 2 diabetes. Adv. Sci. (Weinh) 8, e2100536 (2021). https://doi.org/10.1002/advs.202100536

  142. Everard, A., Belzer, C., Geurts, L., Ouwerkerk, J.P., Druart, C., Bindels, L.B., Guiot, Y., Derrien, M., Muccioli, G.G., Delzenne, N.M., de Vos, W.M., Cani, P.D.: Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proc. Natl. Acad. Sci. USA 110, 9066–9071 (2013). https://doi.org/10.1073/pnas.1219451110

    Article  PubMed  PubMed Central  Google Scholar 

  143. Shin, N.R., Lee, J.C., Lee, H.Y., Kim, M.S., Whon, T.W., Lee, M.S., Bae, J.W.: An increase in the Akkermansia spp. population induced by metformin treatment improves glucose homeostasis in diet-induced obese mice. Gut 63, 727–735 (2014). https://doi.org/10.1136/gutjnl-2012-303839

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Authors and Affiliations

  1. Department of Organic Bio Chemistry, Faculty of Education, Wakayama University, 930, Sakaedani, Wakayama, 640-8510, Japan

    Masanori Yamaguchi

  2. Center for Innovative and Joint Research, Wakayama University, 930, Sakaedani, Wakayama, 640-8510, Japan

    Kenji Yamamoto

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M. Yamaguchi and K. Yamamoto wrote the main manuscript text, and we prepared all figures and table. All authors reviewed the manuscript.

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Correspondence to Masanori Yamaguchi.

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Yamaguchi, M., Yamamoto, K. Mucin glycans and their degradation by gut microbiota. Glycoconj J 40, 493–512 (2023). https://doi.org/10.1007/s10719-023-10124-9

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