Journal of Shanghai Jiao Tong University (Medical Science) >

2022 , Vol. 42 >Issue 10: 1490 - 1497

DOI: https://doi.org/10.3969/j.issn.1674-8115.2022.10.016

Review

Research progress in the role of Akkermansia muciniphila in gut-related diseases

  • Yi JIANG ,
  • Ping JIANG ,
  • Mingming ZHANG ,
  • Jingyuan FANG
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  • 1.Shanghai Institute of Digestive Disease, Department of Gastroenterology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200001, China
    2.Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210093, China
FANG Jingyuan, E-mail: jingyuanfang@sjtu.edu.cn.

Received date: 2022-05-07

  Accepted date: 2022-08-28

  Online published: 2022-10-17

Supported by

National Natural Science Foundation of China(81970487)

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Abstract

Akkermansia muciniphila (A. muciniphila) is one of the normal gut symbionts using mucin as the sole source of carbon and nitrogen elements to maintain colonization and growth. Intestinal homeostasis is crucial for maintaining physiological functions. Intestinal dysfunction is closely related to the occurrence and development of metabolic diseases, immune diseases, infectious diseases and tumors. Gut microbiota is a key factor that influences the intestinal health. As a member of the gut microbes, A. muciniphila plays a convincing role in intestinal inflammation, intestinal tumor and other intestinal disorders involving diseases such as liver diseases and metabolic diseases. The mechanism is under exploration and revealed gradually. Hence, A. muciniphila is considered to be a promising candidate of probiotics. The characteristics of A. muciniphila, its distribution in the gut, its relationship with gut-related diseases and the mechanism are reviewed.

Key words： Akkermansia muciniphila (A. muciniphila); inflammation; tumor; probiotics; gut microbiota

Cite this article

Yi JIANG , Ping JIANG , Mingming ZHANG , Jingyuan FANG . Research progress in the role of Akkermansia muciniphila in gut-related diseases[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2022 , 42(10) : 1490 -1497 . DOI: 10.3969/j.issn.1674-8115.2022.10.016

References

1 LYNCH S V, PEDERSEN O. The human intestinal microbiome in health and disease[J]. N Engl J Med, 2016, 375(24): 2369-2379.
2 JAKOBSSON H E, ABRAHAMSSON T R, JENMALM M C, et al. Decreased gut microbiota diversity, delayed Bacteroidetes colonisation and reduced Th1 responses in infants delivered by caesarean section[J]. Gut, 2014, 63(4): 559-566.
3 DERRIEN M, COLLADO M C, BEN-AMOR K, et al. The Mucin degrader Akkermansia muciniphila is an abundant resident of the human intestinal tract[J]. Appl Environ Microbiol, 2008, 74(5): 1646-1648.
4 DERRIEN M, VAUGHAN E E, PLUGGE C M, et al. Akkermansia muciniphila gen. nov., sp. nov., a human intestinal mucin-degrading bacterium[J]. Int J Syst Evol Microbiol, 2004, 54(Pt 5): 1469-1476.
5 HOLD G L, PRYDE S E, RUSSELL V J, et al. Assessment of microbial diversity in human colonic samples by 16S rDNA sequence analysis[J]. FEMS Microbiol Ecol, 2002, 39(1): 33-39.
6 SALZMAN N H, DE JONG H, PATERSON Y, et al. Analysis of 16S libraries of mouse gastrointestinal microflora reveals a large new group of mouse intestinal bacteria[J]. Microbiology (Reading), 2002, 148(Pt 11): 3651-3660.
7 DERRIEN M, VAN PASSEL M W, VAN DE BOVENKAMP J H, et al. Mucin-bacterial interactions in the human oral cavity and digestive tract[J]. Gut Microbes, 2010, 1(4): 254-268.
8 COLLADO M C, DERRIEN M, ISOLAURI E, et al. Intestinal integrity and Akkermansia muciniphila, a mucin-degrading member of the intestinal microbiota present in infants, adults, and the elderly[J]. Appl Environ Microbiol, 2007, 73(23): 7767-7770.
9 COLLADO M C, ISOLAURI E, LAITINEN K, et al. Distinct composition of gut microbiota during pregnancy in overweight and normal-weight women[J]. Am J Clin Nutr, 2008, 88(4): 894-899.
10 SONOYAMA K, FUJIWARA R, TAKEMURA N, et al. Response of gut microbiota to fasting and hibernation in Syrian hamsters[J]. Appl Environ Microbiol, 2009, 75(20): 6451-6456.
11 BELZER C, DE VOS W M. Microbes inside: from diversity to function: the case of Akkermansia[J]. ISME J, 2012, 6(8): 1449-1458.
12 VAN PASSEL M W J, KANT R, ZOETENDAL E G, et al. The genome of Akkermansia muciniphila, a dedicated intestinal mucin degrader, and its use in exploring intestinal metagenomes[J]. PLoS One, 2011, 6(3): e16876.
13 BAJER L, KVERKA M, KOSTOVCIK M, et al. Distinct gut microbiota profiles in patients with primary sclerosing cholangitis and ulcerative colitis[J]. World J Gastroenterol, 2017, 23(25): 4548-4558.
14 EARLEY H, LENNON G, BALFE á, et al. The abundance of Akkermansia muciniphila and its relationship with sulphated colonic mucins in health and ulcerative colitis[J]. Sci Rep, 2019, 9(1): 15683.
15 KUMP P, WURM P, GR?CHENIG H P, et al. The taxonomic composition of the donor intestinal microbiota is a major factor influencing the efficacy of faecal microbiota transplantation in therapy refractory ulcerative colitis[J]. Aliment Pharmacol Ther, 2018, 47(1): 67-77.
16 PNG C W, LINDéN S K, GILSHENAN K S, et al. Mucolytic bacteria with increased prevalence in IBD mucosa augment in vitro utilization of mucin by other bacteria[J]. Am J Gastroenterol, 2010, 105(11): 2420-2428.
17 BIAN X Y, WU W R, YANG L Y, et al. Administration of Akkermansia muciniphila ameliorates dextran sulfate sodium-induced ulcerative colitis in mice[J]. Front Microbiol, 2019, 10: 2259.
18 KANG C S, BAN M, CHOI E J, et al. Extracellular vesicles derived from gut microbiota, especially Akkermansia muciniphila, protect the progression of dextran sulfate sodium-induced colitis[J]. PLoS One, 2013, 8(10): e76520.
19 WANG L J, TANG L, FENG Y M, et al. A purified membrane protein from Akkermansia muciniphila or the pasteurised bacterium blunts colitis associated tumourigenesis by modulation of CD8+ T cells in mice[J]. Gut, 2020, 69(11): 1988-1997.
20 H?KANSSON ?, TORMO-BADIA N, BARIDI A, et al. Immunological alteration and changes of gut microbiota after dextran sulfate sodium (DSS) administration in mice[J]. Clin Exp Med, 2015, 15(1): 107-120.
21 CASTRO-MEJíA J, JAKESEVIC M, KRYCH ?, et al. Treatment with a monoclonal anti-IL-12p40 antibody induces substantial gut microbiota changes in an experimental colitis model[J]. Gastroenterol Res Pract, 2016, 2016: 4953120.
22 GANESH B P, KLOPFLEISCH R, LOH G, et al. Commensal Akkermansia muciniphila exacerbates gut inflammation in Salmonella Typhimurium-infected gnotobiotic mice[J]. PLoS One, 2013, 8(9): e74963.
23 SEREGIN S S, GOLOVCHENKO N, SCHAF B, et al. NLRP6 protects Il10 -/- mice from colitis by limiting colonization of Akkermansia muciniphila[J]. Cell Rep, 2017, 19(4): 733-745.
24 BAE M, CASSILLY C D, LIU X, et al. Akkermansia muciniphila phospholipid induces homeostatic immune responses[J]. Nature, 2022, 608(7921): 168-173.
25 FAN L N, XU C C, GE Q W, et al. A. muciniphila suppresses colorectal tumorigenesis by inducing TLR2/NLRP3-mediated M1-like TAMs[J]. Cancer Immunol Res, 2021, 9(10): 1111-1124.
26 COLLINS D, HOGAN A M, WINTER D C. Microbial and viral pathogens in colorectal cancer[J]. Lancet Oncol, 2011, 12(5): 504-512.
27 ROUTY B, LE CHATELIER E, DEROSA L, et al. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors[J]. Science, 2018, 359(6371): 91-97.
28 HOU X Y, ZHANG P, DU H Z, et al. Akkermansia muciniphila potentiates the antitumor efficacy of FOLFOX in colon cancer[J]. Front Pharmacol, 2021, 12: 725583.
29 MILOSEVIC I, VUJOVIC A, BARAC A, et al. Gut-liver axis, gut microbiota, and its modulation in the management of liver diseases: a review of the literature[J]. Int J Mol Sci, 2019, 20(2): 395.
30 GRANDER C, ADOLPH T E, WIESER V, et al. Recovery of ethanol-induced Akkermansia muciniphila depletion ameliorates alcoholic liver disease[J]. Gut, 2018, 67(5): 891-901.
31 WU W R, LV L X, SHI D, et al. Protective effect of Akkermansia muciniphila against immune-mediated liver injury in a mouse model[J]. Front Microbiol, 2017, 8: 1804.
32 FAN Y, PEDERSEN O. Gut microbiota in human metabolic health and disease[J]. Nat Rev Microbiol, 2021, 19(1): 55-71.
33 EVERARD A, BELZER C, GEURTS L, et al. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity[J]. Proc Natl Acad Sci USA, 2013, 110(22): 9066-9071.
34 SANTACRUZ A, COLLADO M C, GARCíA-VALDéS L, et al. Gut microbiota composition is associated with body weight, weight gain and biochemical parameters in pregnant women[J]. Br J Nutr, 2010, 104(1): 83-92.
35 KARLSSON C L J, ONNERF?LT J, XU J, et al. The microbiota of the gut in preschool children with normal and excessive body weight[J]. Obesity (Silver Spring), 2012, 20(11): 2257-2261.
36 ZHANG X Y, SHEN D Q, FANG Z W, et al. Human gut microbiota changes reveal the progression of glucose intolerance[J]. PLoS One, 2013, 8(8): e71108.
37 CHELAKKOT C, CHOI Y, KIM D K, et al. Akkermansia muciniphila-derived extracellular vesicles influence gut permeability through the regulation of tight junctions[J]. Exp Mol Med, 2018, 50(2): e450.
38 DAO M C, 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[J]. Gut, 2016, 65(3): 426-436.
39 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[J]. Nat Med, 2017, 23(1): 107-113.
40 LEE H, KO G. Effect of metformin on metabolic improvement and gut microbiota[J]. Appl Environ Microbiol, 2014, 80(19): 5935-5943.
41 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[J]. Gut, 2014, 63(5): 727-735.
42 LI J, LIN S Q, VANHOUTTE P M, et al. Akkermansia muciniphila protects against atherosclerosis by preventing metabolic endotoxemia-induced inflammation in Apoe -/- mice[J]. Circulation, 2016, 133(24): 2434-2446.
43 ZHU L D, LU X X, LIU L, et al. Akkermansia muciniphila protects intestinal mucosa from damage caused by S. pullorum by initiating proliferation of intestinal epithelium[J]. Vet Res, 2020, 51(1): 34.
44 REUNANEN J, KAINULAINEN V, HUUSKONEN L, et al. Akkermansia muciniphila adheres to enterocytes and strengthens the integrity of the epithelial cell layer[J]. Appl Environ Microbiol, 2015, 81(11): 3655-3662.
45 ALAM A, LEONI G, QUIROS M, et al. The microenvironment of injured murine gut elicits a local pro-restitutive microbiota[J]. Nat Microbiol, 2016, 1: 15021.
46 GREGORIEFF A, PINTO D, BEGTHEL H, et al. Expression pattern of Wnt signaling components in the adult intestine[J]. Gastroenterology, 2005, 129(2): 626-638.
47 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[J]. Front Microbiol, 2011, 2: 166.
48 ANSALDO E, SLAYDEN L C, CHING K L, et al. Akkermansia muciniphila induces intestinal adaptive immune responses during homeostasis[J]. Science, 2019, 364(6446): 1179-1184.
49 MASLOWSKI K M, VIEIRA A T, NG A, et al. Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43[J]. Nature, 2009, 461(7268): 1282-1286.
50 KIM M, FRIESEN L, PARK J, et al. Microbial metabolites, short-chain fatty acids, restrain tissue bacterial load, chronic inflammation, and associated cancer in the colon of mice[J]. Eur J Immunol, 2018, 48(7): 1235-1247.
51 MENG X, ZHANG J R, WU H, et al. Akkermansia muciniphila aspartic protease Amuc_1434* inhibits human colorectal cancer LS174T cell viability via TRAIL-mediated apoptosis pathway[J]. Int J Mol Sci, 2020, 21(9): 3385.
52 CARIO E, GERKEN G, PODOLSKY D K. Toll-like receptor 2 controls mucosal inflammation by regulating epithelial barrier function[J]. Gastroenterology, 2007, 132(4): 1359-1374.
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