The unique functionality of Akkermansia muciniphila in gut microbiota indicates it to be an indispensable microbe for human welfare. The importance of A. muciniphila lies in its potential to convert mucin into beneficial by-products, regulate intestinal homeostasis and maintain gut barrier integrity. It is also known to competitively inhibit other mucin-degrading bacteria and improve metabolic functions and immunity responses in the host. It finds a pivotal perspective in various diseases and their treatment. It has future as a promising probiotic, disease biomarker and therapeutic agent for chronic diseases. Disease-associated dysbiosis of A. muciniphila in the gut microbiome makes it a potential candidate as a biomarker for some diseases and can provide future theranostics by suggesting ways of diagnosis for the patients and best treatment method based on the screening results. Manipulation of A. muciniphila in gut microbiome may help in developing a novel personalized therapeutic action and can be a suitable next generation medicine. However, the actual pathway governing A. muciniphila interaction with hosts remains to be investigated. Also, due to the limited availability of products containing A. muciniphila, it is not exploited to its full potential. The present review aims at highlighting the potential of A. muciniphila in mucin degradation, contribution towards the gut health and host immunity and management of metabolic diseases such as obesity and type 2 diabetes, and respiratory diseases such as cystic fibrosis and COVID-19.

Department of Biotechnology Delhi Technological University Delhi 110042 India

Zobrazit více v PubMed

Allin KH, Tremaroli V, Caesar R, et al. Aberrant intestinal microbiota in individuals with prediabetes. Diabetologia. 2018;61:810–820. doi: 10.1007/s00125-018-4550-1. PubMed DOI PMC

Ambort D, Johansson MEV, Gustafsson JK, et al. Calcium and pH-dependent packing and release of the gel-forming MUC2 mucin. Proc Natl Acad Sci. 2012;109:5645–5650. doi: 10.1073/pnas.1120269109. PubMed DOI PMC

Andersson KE, Axling U, Xu J, 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. 2012;52:1755–1769. doi: 10.1007/s00394-012-0479-1. PubMed DOI

Bajer L, Kverka M, Kostovcik M, et al. Distinct gut microbiota profiles in patients with primary sclerosing cholangitis and ulcerative colitis. World J Gastroenterol. 2017;23:4548. doi: 10.3748/wjg.v23.i25.4548. PubMed DOI PMC

Bazett M, Bergeron ME, Haston CK. Streptomycin treatment alters the intestinal microbiome, pulmonary T cell profile and airway hyperresponsiveness in a cystic fibrosis mouse model. Sci Rep. 2016;6:1–13. doi: 10.1038/srep19189. PubMed DOI PMC

Bedarf JR, Hildebrand F, Coelho LP, et al. Erratum to: functional implications of microbial and viral gut metagenome changes in early stage L-DOPA-naïve Parkinson’s disease patients. Genome Med. 2017;9:61. doi: 10.1186/s13073-017-0451-z. PubMed DOI PMC

Belzer C, de Vos WM. Microbes inside—from diversity to function: the case of Akkermansia. ISME J. 2012;6:1449–1458. doi: 10.1038/ismej.2012.6. PubMed DOI PMC

Bernardo D, Sánchez B, Al-Hassi HO, et al. Microbiota/host crosstalk biomarkers: regulatory response of human intestinal dendritic cells exposed to lactobacillus extracellular encrypted peptide. PLoS ONE. 2012;7:e36262. doi: 10.1371/journal.pone.0036262. PubMed DOI PMC

Caesar R, Tremaroli V, Kovatcheva-Datchary P, et al. Crosstalk between gut microbiota and dietary lipids aggravates WAT inflammation through TLR signaling. Cell Metab. 2015;22:658–668. doi: 10.1016/j.cmet.2015.07.026. PubMed DOI PMC

Candela M, Rampelli S, Turroni S, et al. Unbalance of intestinal microbiota in atopic children. BMC Microbiol. 2012;12:95. doi: 10.1186/1471-2180-12-95. PubMed DOI PMC

Cani PD, de Vos WM. Next-generation beneficial microbes: the case of Akkermansia muciniphila. Front Microbiol. 2017 doi: 10.3389/fmicb.2017.01765. PubMed DOI PMC

Cantarel BL, Waubant E, Chehoud C, et al. Gut microbiota in multiple sclerosis. J Investig Med. 2015;63:729–734. doi: 10.1097/JIM.0000000000000192. PubMed DOI PMC

Chelakkot C, Choi Y, Kim D-K, et al. Akkermansia muciniphila-derived extracellular vesicles influence gut permeability through the regulation of tight junctions. Exp Mol Med. 2018;50:e450–e450. doi: 10.1038/emm.2017.282. PubMed DOI PMC

Chen X, Song S, Zhao Y, et al. 146P A new biomarker of microbe: Akkermansia muciniphila in lung adenocarcinoma tissues may predict lymph node metastasis in lung adenocarcinoma. Ann Oncol. 2020;31:S297–S298. doi: 10.1016/j.annonc.2020.08.267. DOI

Chen Z, Qian X, Chen S, et al. Akkermansia muciniphila enhances the antitumor effect of cisplatin in lewis lung cancer mice. J Immunol Res. 2020;2020:1–13. doi: 10.1155/2020/2969287. PubMed DOI PMC

Collado MC, Isolauri E, Laitinen K, Salminen S. Distinct composition of gut microbiota during pregnancy in overweight and normal-weight women. Am J Clin Nutr. 2008;88:894–899. doi: 10.1093/ajcn/88.4.894. PubMed DOI

Collado MC, Laitinen K, Salminen S, Isolauri E. Maternal weight and excessive weight gain during pregnancy modify the immunomodulatory potential of breast milk. Pediatr Res. 2012;72:77–85. doi: 10.1038/pr.2012.42. PubMed DOI

Cone RA. Barrier properties of mucus. Adv Drug Deliv Rev. 2009;61:75–85. doi: 10.1016/j.addr.2008.09.008. PubMed DOI

Cronin P, Joyce SA, O’Toole PW, O’Connor EM. Dietary fibre modulates the gut microbiota. Nutrients. 2021;13:1655. doi: 10.3390/nu13051655. PubMed DOI PMC

Dao MC, Everard A, Aron-Wisnewsky J, et al. Akkermansia muciniphila and improved metabolic health during a dietary intervention in obesity: relationship with gut microbiome richness and ecology. Gut. 2016;65:426–436. doi: 10.1136/gutjnl-2014-308778. PubMed DOI

De Angelis M, Piccolo M, Vannini L, et al. Fecal microbiota and metabolome of children with autism and pervasive developmental disorder not otherwise specified. PLoS ONE. 2013;8:e76993. doi: 10.1371/journal.pone.0076993. PubMed DOI PMC

Dean M, Annilo T. Evolution of the atp-binding cassette (ABC) transporter superfamily in vertebrates. Annu Rev Genomics Hum Genet. 2005;6:123–142. doi: 10.1146/annurev.genom.6.080604.162122. PubMed DOI

Demirci M, Tokman HB, Uysal HK, et al. Reduced Akkermansia muciniphila and Faecalibacterium prausnitzii levels in the gut microbiota of children with allergic asthma. Allergol Immunopathol (madr) 2019;47:365–371. doi: 10.1016/j.aller.2018.12.009. PubMed DOI

Depommier C, Everard A, Druart C, et al. Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study. Nat Med. 2019;25:1096–1103. doi: 10.1038/s41591-019-0495-2. PubMed DOI PMC

Derrien M, Van Baarlen P, Hooiveld G, et al. Modulation of mucosal immune response, tolerance, and proliferation in mice colonized by the mucin-degrader Akkermansia muciniphila. Front Microbiol. 2011 doi: 10.3389/fmicb.2011.00166. PubMed DOI PMC

Derrien M, Vaughan EE, Plugge CM, de Vos WM. Akkermansia municiphila gen. nov., sp. nov., a human intestinal mucin-degrading bacterium. Int J Syst Evol Microbiol. 2004;54:1469–1476. doi: 10.1099/ijs.0.02873-0. PubMed DOI

Dhar D, Mohanty A. Gut microbiota and COVID-19- possible link and implications. Virus Res. 2020;285:198018. doi: 10.1016/j.virusres.2020.198018. PubMed DOI PMC

Drell T, Larionova A, Voor T, et al. Differences in gut microbiota between atopic and healthy children. Curr Microbiol. 2015;71:177–183. doi: 10.1007/s00284-015-0815-9. PubMed DOI

Everard A, Belzer C, Geurts L, et al. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proc Natl Acad Sci. 2013;110:9066–9071. doi: 10.1073/pnas.1219451110. PubMed DOI PMC

Fassatoui M, Lopez-Siles M, Díaz-Rizzolo DA, et al. Gut microbiota imbalances in Tunisian participants with type 1 and type 2 diabetes mellitus. Biosci Rep. 2019 doi: 10.1042/BSR20182348. PubMed DOI PMC

Fischer H, Holst E, Karlsson F, et al. Altered microbiota in microscopic colitis. Gut. 2015;64:1185–1186. doi: 10.1136/gutjnl-2014-308956. PubMed DOI PMC

Fuke N, Nagata N, Suganuma H, Ota T. Regulation of gut microbiota and metabolic endotoxemia with dietary factors. Nutrients. 2019;11:2277. doi: 10.3390/nu11102277. PubMed DOI PMC

Gao R, Zhu C, Li H, et al. Dysbiosis signatures of gut microbiota along the sequence from healthy, young patients to those with overweight and obesity. Obesity. 2018;26:351–361. doi: 10.1002/oby.22088. PubMed DOI

Gargari G, Deon V, Taverniti V, et al. Evidence of dysbiosis in the intestinal microbial ecosystem of children and adolescents with primary hyperlipidemia and the potential role of regular hazelnut intake. FEMS Microbiol Ecol. 2018 doi: 10.1093/femsec/fiy045. PubMed DOI

Gou W, Fu Y, Yue L, et al. Gut microbiota, inflammation, and molecular signatures of host response to infection. J Genet Genomics. 2021;48:792–802. doi: 10.1016/j.jgg.2021.04.002. PubMed DOI

Grander C, Adolph TE, Wieser V, et al. Recovery of ethanol-induced Akkermansia muciniphila depletion ameliorates alcoholic liver disease. Gut. 2018;67:891–901. doi: 10.1136/gutjnl-2016-313432. PubMed DOI

Gray J, Oehrle K, Worthen G, et al. Intestinal commensal bacteria mediate lung mucosal immunity and promote resistance of newborn mice to infection. Sci Transl Med. 2017;9:eaaf9412. doi: 10.1126/scitranslmed.aaf9412. PubMed DOI PMC

Greer RL, Dong X, Moraes ACF, et al. Akkermansia muciniphila mediates negative effects of IFNγ on glucose metabolism. Nat Commun. 2016;7:13329. doi: 10.1038/ncomms13329. PubMed DOI PMC

Gunderson KL, Kopito RR. Effects of pyrophosphate and nucleotide analogs suggest a role for ATP hydrolysis in cystic fibrosis transmembrane regulator channel gating. J Biol Chem. 1994;269:19349–19353. doi: 10.1016/s0021-9258(17)32174-9. PubMed DOI

Guo X, Li S, Zhang J, et al. Genome sequencing of 39 Akkermansia muciniphila isolates reveals its population structure, genomic and functional diverisity, and global distribution in mammalian gut microbiotas. BMC Genomics. 2017 doi: 10.1186/s12864-017-4195-3. PubMed DOI PMC

Gurung M, Li Z, You H, et al. Role of gut microbiota in type 2 diabetes pathophysiology. EBioMedicine. 2020;51:102590. doi: 10.1016/j.ebiom.2019.11.051. PubMed DOI PMC

Han H, Ma Q, Li C, et al. Profiling serum cytokines in COVID-19 patients reveals IL-6 and IL-10 are disease severity predictors. Emerg Microbes Infect. 2020;9:1123–1130. doi: 10.1080/22221751.2020.1770129. PubMed DOI PMC

Hayden H, Eng A, Pope C, et al. P314 Fecal dysbiosis is associated with growth failure in infants with cystic fibrosis: a multicentre study. J Cyst Fibros. 2019;18:S146. doi: 10.1016/S1569-1993(19)30607-1. DOI

Hoffman LR, Pope CE, Hayden HS, et al. Escherichia coli dysbiosis correlates with gastrointestinal dysfunction in children with cystic fibrosis. Clin Infect Dis. 2014;58:396–399. doi: 10.1093/cid/cit715. PubMed DOI PMC

Hu Y, Feng Y, Wu J, et al. The gut microbiome signatures discriminate healthy from pulmonary tuberculosis patients. Front Cell Infect Microbiol. 2019 doi: 10.3389/fcimb.2019.00090. PubMed DOI PMC

Hussain I, Cher GLY, Abid MA, Abid MB. Role of gut microbiome in COVID-19: an insight into pathogenesis and therapeutic potential. Front Immunol. 2021 doi: 10.3389/fimmu.2021.765965. PubMed DOI PMC

Jakobsson HE, Rodríguez‐Piñeiro AM, Schütte A et al (2015) The composition of the gut microbiota shapes the colon mucus barrier. EMBO Rep 16:164–177. 10.15252/embr.201439263 PubMed PMC

Johansson MEV, Holmén Larsson JM, Hansson GC. 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. 2011;108:4659–4665. doi: 10.1073/pnas.1006451107. PubMed DOI PMC

Johansson MEV, Phillipson M, Petersson J, 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. 2008;105:15064–15069. doi: 10.1073/pnas.0803124105. PubMed DOI PMC

Johansson MEV, Sjövall H, Hansson GC. The gastrointestinal mucus system in health and disease. Nat Rev Gastroenterol Hepatol. 2013;10:352–361. doi: 10.1038/nrgastro.2013.35. PubMed DOI PMC

Karlsson CLJ, Önnerfält J, Xu J, et al. The microbiota of the gut in preschool children with normal and excessive body weight. Obesity. 2012;20:2257–2261. doi: 10.1038/oby.2012.110. PubMed DOI

Kim S, Rigatto K, Gazzana MB, et al. Altered gut microbiome profile in patients with pulmonary arterial hypertension. Hypertension. 2020;75:1063–1071. doi: 10.1161/HYPERTENSIONAHA.119.14294. PubMed DOI PMC

Kuba K, Imai Y, Rao S, et al. A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus–induced lung injury. Nat Med. 2005;11:875–879. doi: 10.1038/nm1267. PubMed DOI PMC

Lee DM, Battson ML, Jarrell DK, et al. SGLT2 inhibition via dapagliflozin improves generalized vascular dysfunction and alters the gut microbiota in type 2 diabetic mice. Cardiovasc Diabetol. 2018;17:62. doi: 10.1186/s12933-018-0708-x. PubMed DOI PMC

Ley RE, Bäckhed F, Turnbaugh P, et al. Obesity alters gut microbial ecology. Proc Natl Acad Sci. 2005;102:11070–11075. doi: 10.1073/pnas.0504978102. PubMed DOI PMC

Li J, Lin S, Vanhoutte PM, et al. Akkermansia muciniphila protects against atherosclerosis by preventing metabolic endotoxemia-induced inflammation in apoe −/− mice. Circulation. 2016;133:2434–2446. doi: 10.1161/CIRCULATIONAHA.115.019645. PubMed DOI

Liu F, Ling Z, Xiao Y et al (2017) Dysbiosis of urinary microbiota is positively correlated with Type 2 diabetes mellitus. Oncotarget 8:3798–3810. 10.18632/oncotarget.14028 PubMed PMC

Lukovac S, Belzer C, Pellis L, et al. Differential modulation by Akkermansia muciniphila and Faecalibacterium prausnitzii of host peripheral lipid metabolism and histone acetylation in mouse gut organoids. Mbio. 2014 doi: 10.1128/mBio.01438-14. PubMed DOI PMC

Malham M, Lilje B, Houen G, et al. The microbiome reflects diagnosis and predicts disease severity in paediatric onset inflammatory bowel disease. Scand J Gastroenterol. 2019;54:969–975. doi: 10.1080/00365521.2019.1644368. PubMed DOI

Manor O, Levy R, Pope CE, et al. Metagenomic evidence for taxonomic dysbiosis and functional imbalance in the gastrointestinal tracts of children with cystic fibrosis. Sci Rep. 2016;6:22493. doi: 10.1038/srep22493. PubMed DOI PMC

Marvasti FE, Moshiri A, Sadat Taghavi M et al (2020) The first report of differences in gut microbiota composition between obese and normal weight iranian subjects. Iran Biomed J 24:148–154. 10.29252/ibj.24.3.148 PubMed PMC

Mattioli AV, Sciomer S, Cocchi C, et al. Quarantine during COVID-19 outbreak: changes in diet and physical activity increase the risk of cardiovascular disease. Nutr Metab Cardiovasc Dis. 2020;30:1409–1417. doi: 10.1016/j.numecd.2020.05.020. PubMed DOI PMC

Meeker SM, Mears KS, Sangwan N, et al. CFTR dysregulation drives active selection of the gut microbiome. PLoS Pathog. 2020;16:e1008251. doi: 10.1371/journal.ppat.1008251. PubMed DOI PMC

Michalovich D, Rodriguez-Perez N, Smolinska S, et al. Obesity and disease severity magnify disturbed microbiome-immune interactions in asthma patients. Nat Commun. 2019;10:5711. doi: 10.1038/s41467-019-13751-9. PubMed DOI PMC

Mira-Pascual L, Cabrera-Rubio R, Ocon S, et al. Microbial mucosal colonic shifts associated with the development of colorectal cancer reveal the presence of different bacterial and archaeal biomarkers. J Gastroenterol. 2015;50:167–179. doi: 10.1007/s00535-014-0963-x. PubMed DOI

Morgan XC, Huttenhower C. Chapter 12: human microbiome analysis. PLoS Comput Biol. 2012;8:e1002808. doi: 10.1371/journal.pcbi.1002808. PubMed DOI PMC

Neef A, Sanz Y. Future for probiotic science in functional food and dietary supplement development. Curr Opin Clin Nutr Metab Care. 2013;16:679–687. doi: 10.1097/MCO.0b013e328365c258. PubMed DOI

Nicholson JK, Holmes E, Kinross J, et al. Host-gut microbiota metabolic interactions. Science. 2012;336:1262–1267. doi: 10.1126/science.1223813. PubMed DOI

Opstelten JL, Plassais J, van Mil SWC, et al. Gut microbial diversity is reduced in smokers with Crohnʼs disease. Inflamm Bowel Dis. 2016;22:2070–2077. doi: 10.1097/MIB.0000000000000875. PubMed DOI PMC

Ottman N, Davids M, Suarez-Diez M, et al. Genomescale model and omics analysis of metabolic capacities of Akkermansia muciniphila reveal a preferential mucin-degrading lifestyle. Appl Environ Microbiol. 2017 doi: 10.1128/AEM.01014-17. PubMed DOI PMC

Ottman N, Reunanen J, Meijerink M, et al. Pili-like proteins of Akkermansia muciniphila modulate host immune responses and gut barrier function. PLoS ONE. 2017 doi: 10.1371/journal.pone.0173004. PubMed DOI PMC

Ouwerkerk JP, van der Ark KCH, Davids M, et al. Adaptation of Akkermansia muciniphila to the oxic-anoxic interface of the mucus layer. Appl Environ Microbiol. 2016;82:6983–6993. doi: 10.1128/AEM.01641-16. PubMed DOI PMC

Pang T, Leach ST, Katz T, et al. Fecal biomarkers of intestinal health and disease in children. Front Pediatr. 2014 doi: 10.3389/fped.2014.00006. PubMed DOI PMC

Peng Y, Zhang S, Liu Z, et al. Gut microbiota and Chinese medicine syndrome: altered fecal microbiotas in spleen (Pi)-deficient patients. J Tradit Chin Med = Chung i Tsa Chih Ying Wen Pan. 2020;40:137–143. PubMed

Plovier H, Everard A, Druart C, et al. A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice. Nat Med. 2016;23:107–113. doi: 10.1038/nm.4236. PubMed DOI

Png CW, Lindén SK, Gilshenan KS, et al. Mucolytic bacteria with increased prevalence in IBD mucosa augment in vitro utilization of mucin by other bacteria. Am J Gastroenterol. 2010;105:2420–2428. doi: 10.1038/ajg.2010.281. PubMed DOI

Price CE, O’Toole GA (2021) The gut-lung axis in cystic fibrosis. J Bacteriol 203 PubMed PMC

Qin J, Li Y, Cai Z, et al. A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature. 2012;490:55–60. doi: 10.1038/nature11450. PubMed DOI

Rajilić-Stojanović M, Shanahan F, Guarner F, de Vos WM. Phylogenetic analysis of dysbiosis in ulcerative colitis during remission. Inflamm Bowel Dis. 2013;19:481–488. doi: 10.1097/MIB.0b013e31827fec6d. PubMed DOI

Remely M, Hippe B, Geretschlaeger I, et al. Increased gut microbiota diversity and abundance of Faecalibacterium prausnitzii and Akkermansia after fasting: a pilot study. Wien Klin Wochenschr. 2015;127:394–398. doi: 10.1007/s00508-015-0755-1. PubMed DOI PMC

Remely M, Hippe B, Zanner J, et al. Gut microbiota of obese, type 2 diabetic individuals is enriched in Faecalibacterium prausnitzii, Akkermansia muciniphila and Peptostreptococcus anaerobius after weight loss. Endocrine, Metab Immune Disord - Drug Targets. 2016;16:99–106. doi: 10.2174/1871530316666160831093813. PubMed DOI

Ruiz L, Hevia A, Bernardo D, et al. Extracellular molecular effectors mediating probiotic attributes. FEMS Microbiol Lett. 2014;359:1–11. doi: 10.1111/1574-6968.12576. PubMed DOI

Salonen A, de Vos WM. Impact of diet on human intestinal microbiota and health. Annu Rev Food Sci Technol. 2014;5:239–262. doi: 10.1146/annurev-food-030212-182554. PubMed DOI

Sánchez B, Bressollier P, Urdaci MC. Exported proteins in probiotic bacteria: adhesion to intestinal surfaces, host immunomodulation and molecular cross-talking with the host. FEMS Immunol Med Microbiol. 2008;54:1–17. doi: 10.1111/j.1574-695x.2008.00454.x. PubMed DOI

Sánchez B, Urdaci MC, Margolles A. Extracellular proteins secreted by probiotic bacteria as mediators of effects that promote mucosa–bacteria interactions. Microbiology. 2010;156:3232–3242. doi: 10.1099/mic.0.044057-0. PubMed DOI

Schippa S, Iebba V, Santangelo F, et al. Cystic fibrosis transmembrane conductance regulator (CFTR) allelic variants relate to shifts in faecal microbiota of cystic fibrosis patients. PLoS ONE. 2013;8:e61176. doi: 10.1371/journal.pone.0061176. PubMed DOI PMC

Schneeberger M, Everard A, Gómez-Valadés AG, et al. Akkermansia muciniphila inversely correlates with the onset of inflammation, altered adipose tissue metabolism and metabolic disorders during obesity in mice. Sci Rep. 2015;5:16643. doi: 10.1038/srep16643. PubMed DOI PMC

Schütte A, Ermund A, Becker-Pauly C, et al. Microbial-induced meprin β cleavage in MUC2 mucin and a functional CFTR channel are required to release anchored small intestinal mucus. Proc Natl Acad Sci. 2014;111:12396–12401. doi: 10.1073/pnas.1407597111. PubMed DOI PMC

Sedighi M, Razavi S, Navab-Moghadam F, et al. Comparison of gut microbiota in adult patients with type 2 diabetes and healthy individuals. Microb Pathog. 2017;111:362–369. doi: 10.1016/j.micpath.2017.08.038. PubMed DOI

Shin J, Noh JR, Chang DH, et al. Elucidation of akkermansia muciniphila probiotic traits driven by mucin depletion. Front Microbiol. 2019 doi: 10.3389/fmicb.2019.01137. PubMed DOI PMC

Shin N-R, Lee J-C, Lee H-Y, et al. An increase in the Akkermansia spp. population induced by metformin treatment improves glucose homeostasis in diet-induced obese mice. Gut. 2014;63:727–735. doi: 10.1136/gutjnl-2012-303839. PubMed DOI

Snider EJ, Compres G, Freedberg DE, et al. Alterations to the esophageal microbiome associated with progression from Barrett’s esophagus to esophageal adenocarcinoma. Cancer Epidemiol Biomarkers Prev. 2019;28:1687–1693. doi: 10.1158/1055-9965.EPI-19-0008. PubMed DOI PMC

Swidsinski A, Dörffel Y, Loening-Baucke V, et al. Acute appendicitis is characterised by local invasion with Fusobacterium nucleatum/necrophorum. Gut. 2011;60:34–40. doi: 10.1136/gut.2009.191320. PubMed DOI

Tan L, Zhao S, Zhu W, et al. The Akkermansia muciniphila is a gut microbiota signature in psoriasis. Exp Dermatol. 2018;27:144–149. doi: 10.1111/exd.13463. PubMed DOI

Thomsson KA, Hinojosa-Kurtzberg M, Axelsson KA, et al. Intestinal mucins from cystic fibrosis mice show increased fucosylation due to an induced Fucα1-2 glycosyltransferase. Biochem J. 2002;367:609–616. doi: 10.1042/BJ20020371. PubMed DOI PMC

Tilg H, Moschen AR. Microbiota and diabetes: an evolving relationship. Gut. 2014;63:1513–1521. doi: 10.1136/gutjnl-2014-306928. PubMed DOI

Tummler B, Puchelle E. CFTR: a multifaceted epithelial molecule. Trends Cell Biol. 1997;6(7):250–251. doi: 10.1016/S0962-8924(97)01062-3. PubMed DOI

Unger MM, Spiegel J, Dillmann K-U, et al. Short chain fatty acids and gut microbiota differ between patients with Parkinson’s disease and age-matched controls. Parkinsonism Relat Disord. 2016;32:66–72. doi: 10.1016/j.parkreldis.2016.08.019. PubMed DOI

Vakili B, Fateh A, Asadzadeh Aghdaei H, et al. Characterization of gut microbiota in hospitalized patients with clostridioides difficile infection. Curr Microbiol. 2020;77:1673–1680. doi: 10.1007/s00284-020-01980-x. PubMed DOI

van der Ark KCH, Aalvink S, Suarez-Diez M, et al. Model-driven design of a minimal medium for Akkermansia muciniphila confirms mucus adaptation. Microb Biotechnol. 2018;11:476–485. doi: 10.1111/1751-7915.13033. PubMed DOI PMC

van Passel MWJ, Kant R, Zoetendal EG, et al. The genome of Akkermansia muciniphila, a dedicated intestinal mucin degrader, and its use in exploring intestinal metagenomes. PLoS ONE. 2011 doi: 10.1371/journal.pone.0016876. PubMed DOI PMC

Vernocchi P, Del CF, Russo A, et al. Gut microbiota signatures in cystic fibrosis: Loss of host CFTR function drives the microbiota enterophenotype. PLoS ONE. 2018;13:e0208171. doi: 10.1371/journal.pone.0208171. PubMed DOI PMC

Wan L, Zhou X, Wang C, et al. Alterations of the gut microbiota in multiple system atrophy patients. Front Neurosci. 2019 doi: 10.3389/fnins.2019.01102. PubMed DOI PMC

Wang H, Wang H, Sun Y, et al. Potential associations between microbiome and COVID-19. Front Med. 2021 doi: 10.3389/fmed.2021.785496. PubMed DOI PMC

Wang J, Jia H. Metagenomewide association studies: fine-mining the microbiome. Nat Rev Microbiol. 2016;14:508–522. doi: 10.1038/nrmicro.2016.83. PubMed DOI

Wang J, Tang H, Zhang C, et al. Modulation of gut microbiota during probiotic-mediated attenuation of metabolic syndrome in high fat diet-fed mice. ISME J. 2015;9:1–15. doi: 10.1038/ismej.2014.99. PubMed DOI PMC

Wang L, Christophersen CT, Sorich MJ, et al. Low relative abundances of the mucolytic bacterium Akkermansia muciniphila and Bifidobacterium spp. in Feces of children with autism. Appl Environ Microbiol. 2011;77:6718–6721. doi: 10.1128/AEM.05212-11. PubMed DOI PMC

Wang Z, Saha S, Van Horn S, et al. Gut microbiome differences between metformin- and liraglutide-treated T2DM subjects. Endocrinol Diabetes Metab. 2018;1:e00009. doi: 10.1002/edm2.9. PubMed DOI PMC

Weir TL, Manter DK, Sheflin AM, et al. Stool microbiome and metabolome differences between colorectal cancer patients and healthy adults. PLoS ONE. 2013;8:e70803. doi: 10.1371/journal.pone.0070803. PubMed DOI PMC

Welsh MJ, Smith AE. Molecular mechanisms of CFTR chloride channel dysfunction in cystic fibrosis. Cell. 1993;73:1251–1254. doi: 10.1016/0092-8674(93)90353-R. PubMed DOI

Xiao F, Sun J, Xu Y, et al. Infectious SARS-CoV-2 in feces of patient with severe COVID-19. Emerg Infect Dis. 2020;26:1920–1922. doi: 10.3201/eid2608.200681. PubMed DOI PMC

Xu R, Wu B, Liang J, et al. Altered gut microbiota and mucosal immunity in patients with schizophrenia. Brain Behav Immun. 2020;85:120–127. doi: 10.1016/j.bbi.2019.06.039. PubMed DOI

Xu Y, Wang N, Tan H-Y, et al. Function of Akkermansia muciniphila in obesity: interactions with lipid metabolism, immune response and gut systems. Front Microbiol. 2020 doi: 10.3389/fmicb.2020.00219. PubMed DOI PMC

Yamamoto S, Saito M, Tamura A, Prawisuda D, Mizutani T, Yotsuyanagi H. The human microbiome and COVID-19: a systematic review. PLoS ONE. 2021;16(6):e0253293. doi: 10.1371/journal.pone.0253293. PubMed DOI PMC

Yeoh YK, Zuo T, Lui GC-Y, et al. Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID-19. Gut. 2021;70:698–706. doi: 10.1136/gutjnl-2020-323020. PubMed DOI PMC

Yu J, Feng Q, Wong SH, et al. Metagenomic analysis of faecal microbiome as a tool towards targeted non-invasive biomarkers for colorectal cancer. Gut. 2017;66:70–78. doi: 10.1136/gutjnl-2015-309800. PubMed DOI

Zhang L, Qin Q, Liu M, et al. Akkermansia muciniphila can reduce the damage of gluco/lipotoxicity, oxidative stress and inflammation, and normalize intestine microbiota in streptozotocin-induced diabetic rats. Pathog Dis. 2018 doi: 10.1093/femspd/fty028. PubMed DOI

Zhong H, Ren H, Lu Y, et al. Distinct gut metagenomics and metaproteomics signatures in prediabetics and treatment-naïve type 2 diabetics. EBioMedicine. 2019;47:373–383. doi: 10.1016/j.ebiom.2019.08.048. PubMed DOI PMC

Zhu F, Ju Y, Wang W, et al. Metagenome-wide association of gut microbiome features for schizophrenia. Nat Commun. 2020;11:1612. doi: 10.1038/s41467-020-15457-9. PubMed DOI PMC

Zoetendal EG, Raes J, van den Bogert B, et al. The human small intestinal microbiota is driven by rapid uptake and conversion of simple carbohydrates. ISME J. 2012;6:1415–1426. doi: 10.1038/ismej.2011.212. PubMed DOI PMC