Role of Akkermansia muciniphila in diabetes and obesity
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    Abstract:

    Gut microbiota plays a significant role in the balance between health and disease. Akkermansia muciniphila is one of the intestinal bacteria and its specialization in mucin degradation makes it a key organism at the mucosal interface between the lumen and host cells. A. muciniphila is found inversely associated with obesity, diabetes, cardiometabolic diseases and low-grade inflammation. Oral administration of A. muciniphila reduces the symptoms of metabolic disease in mice. Therefore, A. muciniphila is a promising candidate for the treatment of diabetes and obesity. Here, we summarize the existing data on A. muciniphila and its role in diabetes and obesity, to provide insight into the intricate mechanisms of A. muciniphila regulation of the cross-talk between the host and gut microbiota, so as to provide ideas for further research on A. muciniphila bacteria and the development of new drugs for diabetes.

    Reference
    [1] Belzer C, de Vos WM. Microbes inside-from diversity to function:the case of Akkermansia. The ISME Journal Volume, 2012, 6(8):1449-1458.
    [2] Derrien M, Vaughan EE, Plugge CM, de Vos WM. Akkermansia muciniphila gen. nov., sp. nov., a human intestinal mucin-degrading bacterium. International Journal of Systematic and Evolutionary Microbiology, 2004, 54(5):1469-1476.
    [3] Grześkowiak L, Grönlund MM, Beckmann C, Salminen S, von Berg A, Isolauri E. The impact of perinatal probiotic intervention on gut microbiota:double-blind placebo-controlled trials in Finland and Germany. Anaerobe, 2012, 18(1):7-13.
    [4] Derrien M, Collado MC, Ben-Amor K, Salminen S, de Vos WM. The Mucin degrader Akkermansia muciniphila is an abundant resident of the human intestinal tract. Applied and Environmental Microbiology, 2008, 74(5):1646-1648.
    [5] Johansson MEV, Larsson JMH, 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. Proceedings of the National Academy of Sciences of the United States of America, 2011, 108(S1):4659-4665.
    [6] Sicard JF, Le Bihan G, Vogeleer P, Jacques M, Harel J. Interactions of intestinal bacteria with components of the intestinal mucus. Frontiers in Cellular and Infection Microbiology, 2017, 7:387.
    [7] van Passel MWJ, Kant R, Zoetendal EG, Plugge CM, Derrien M, Malfatti SA, Chain PSG, Woyke T, Palva A, de Vos WM, Smidt H. The genome of Akkermansia muciniphila, a dedicated intestinal mucin degrader, and its use in exploring intestinal metagenomes. PLoS One, 2011, 6(3):e16876.
    [8] Plovier H, Everard A, Druart C, Depommier C, van Hul M, Geurts L, Chilloux J, Ottman N, Duparc T, Lichtenstein L, Myridakis A, Delzenne NM, Klievink J, Bhattacharjee A, van der Ark KCH, Aalvink S, Martinez LO, Dumas ME, Maiter D, Loumaye A, Hermans MP, Thissen JP, Belzer C, de Vos WM, Cani PD. A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice. Nature Medicine, 2017, 23(1):107-113.
    [9] Schneeberger M, Everard A, Gómez-Valadés AG, Matamoros S, Ramírez S, Delzenne NM, Gomis R, Claret M, Cani PD. Akkermansia muciniphila inversely correlates with the onset of inflammation, altered adipose tissue metabolism and metabolic disorders during obesity in mice. Scientific Reports, 2015, 5:16643.
    [10] Li J, Lin SQ, Vanhoutte PM, Woo CW, Xu AM. Akkermansia muciniphila protects against atherosclerosis by preventing metabolic endotoxemia-induced inflammation in Apoe-/- Mice. Circulation, 2016, 133(24):2434-2446.
    [11] O'Toole PW, Marchesi JR, Hill C. Next-generation probiotics:the spectrum from probiotics to live biotherapeutics. Nature Microbiology, 2017, 2(5):17057.
    [12] Zhang XY, Shen DQ, Fang ZW, Jie ZY, Qiu XM, Zhang CF, Chen YL, Ji LN. Human gut microbiota changes reveal the progression of glucose intolerance. PLoS One, 2013, 8(8):e71108.
    [13] Everard A, Belzer C, Geurts L, Ouwerkerk JP, Druart C, Bindels LB, Guiot Y, Derrien M, Muccioli GG, Delzenne NM, de Vos WM, Cani PD. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proceedings of the National Academy of Sciences of the United States of America, 2013, 110(22):9066-9071.
    [14] Bischoff SC, Barbara G, Buurman W, Ockhuizen T, Schulzke JD, Serino M, Tilg H, Watson A, Wells JM. Intestinal permeability-a new target for disease prevention and therapy. BMC Gastroenterology, 2014, 14:189.
    [15] Khan N, Asif AR. Transcriptional regulators of claudins in epithelial tight junctions. Mediators of Inflammation, 2015, 2015:219843.
    [16] Groschwitz KR, Hogan SP. Intestinal barrier function:molecular regulation and disease pathogenesis. Journal of Allergy and Clinical Immunology, 2009, 124(1):3-20.
    [17] Viggiano D, Ianiro G, Vanella G, Bibbò S, Bruno G, Simeone G, Mele G. Gut barrier in health and disease:focus on childhood. European Review for Medical and Pharmacological Sciences, 2015, 19(6):1077-1085.
    [18] Camilleri M, Madsen K, Spiller R, van Meerveld BG, Verne GN. Intestinal barrier function in health and gastrointestinal disease. Neurogastroenterology & Motility, 2012, 24(6):503-512.
    [19] Heyman M, Abed J, Lebreton C, Cerf-Bensussan N. Intestinal permeability in coeliac disease:insight into mechanisms and relevance to pathogenesis. Gut, 2012, 61(9):1355-1364.
    [20] Chelakkot C, Choi Y, Kim DK, Park HT, Ghim J, Kwon Y, Jeon J, Kim MS, Jee YK, Gho YS, Park HS, Kim YK, Ryu SH. Akkermansia muciniphila-derived extracellular vesicles influence gut permeability through the regulation of tight junctions. Experimental & Molecular Medicine, 2018, 50(2):e450.
    [21] Ottman N, Reunanen J, Meijerink M, Pietilä TE, Kainulainen V, Klievink J, Huuskonen L, Aalvink S, Skurnik M, Boeren S, Satokari R, Mercenier A, Palva A, Smidt H, de Vos WM, Belzer C. Pili-like proteins of Akkermansia muciniphila modulate host immune responses and gut barrier function. PLoS One, 2017, 12(3):e0173004.
    [22] Reunanen J, Kainulainen V, Huuskonen L, Ottman N, Belzer C, Huhtinen H, de Vos WM, Satokari R. Akkermansia muciniphila adheres to enterocytes and strengthens the integrity of the epithelial cell layer. Applied and Environmental Microbiology, 2015, 81(11):3655-3662.
    [23] Harbison JE, Roth-Schulze AJ, Barry SC, Tran CD, Ngui K, Penno MA, Wentworth J, Colman PG, Thomson R, Craig ME, Papenfuss AT, Giles L, Harrison LC, Couper J. Gut microbiome dysbiosis and increased intestinal permeability in Australian children with islet autoimmunity and type 1 diabetes. Diabetes, 2018, 6(S1):71.
    [24] Hänninen A, Toivonen R, Pöysti S, Belzer C, Plovier H, Ouwerkerk JP, Emani R, Cani PD, de Vos WM. Akkermansia muciniphila induces gut microbiota remodelling and controls islet autoimmunity in NOD mice. Gut, 2018, 67(8):1445-1453.
    [25] Muccioli GG, Naslain D, Bäckhed F, Reigstad CS, Lambert DM, Delzenne NM, Cani PD. The endocannabinoid system links gut microbiota to adipogenesis. Molecular Systems Biology, 2010, 6:392.
    [26] Lu D, Dopart R, Kendall DA. Controlled downregulation of the cannabinoid CB1 receptor provides a promising approach for the treatment of obesity and obesity-derived type 2 diabetes. Cell Stress and Chaperones, 2016, 21(1):1-7.
    [27] Liu J, Bátkai S, Pacher P, Harvey-White J, Wagner JA, Cravatt BF, Gao B, Kunos G. Lipopolysaccharide induces anandamide synthesis in macrophages via CD14/MAPK/phosphoinositide 3-kinase/NF-κB independently of platelet-activating factor. The Journal of Biological Chemistry, 2003, 278(45):45034-45039.
    [28] Mehrpouya-Bahrami P, Chitrala KN, Ganewatta MS, Tang CB, Murphy EA, Enos RT, Velazquez KT, McCellan J, Nagarkatti M, Nagarkatti P. Blockade of CB1 cannabinoid receptor alters gut microbiota and attenuates inflammation and diet-induced obesity. Scientific Reports, 2017, 7(1):15645.
    [29] Koh A, de Vadder F, Kovatcheva-Datchary P, Bäckhed F. From dietary fiber to host physiology:short-chain fatty acids as key bacterial metabolites. Cell, 2016, 165(6):1332-1345.
    [30] Sanna S, van Zuydam NR, Mahajan A, Kurilshikov A, Vila VA, Võsa U, Mujagic Z, Masclee AM, Jonkers DMAE, Oosting M, Joosten LAB, Netea MG, Franke L, Zhernakova A, Fu JY, Wijmenga C, McCarthy MI. Causal relationships among the gut microbiome, short-chain fatty acids and metabolic diseases. Nature Genetics, 2019, 51(4):600-605.
    [31] Ottman N, Davids M, Suarez-Diez M, Boeren S, Schaap PJ, Martins dos Santos VAP, Smidt H, Belzer C, de Vos WM. Genome-Scale model and omics analysis of metabolic capacities of Akkermansia muciniphila reveal a preferential mucin-degrading lifestyle. Applied and Environmental Microbiology, 2017, 83(18):e01014-17.
    [32] Belzer C, Chia LW, Aalvink S, Chamlagain B, Piironen V, Knol J, de Vos WM. Microbial metabolic networks at the mucus layer lead to diet-independent butyrate and vitamin B12 production by intestinal symbionts. mBio, 2017, 8(5):e00770-17.
    [33] Chia LW, Hornung BVH, Aalvink S, Schaap PJ, de Vos WM, Knol J, Belzer C. Deciphering the trophic interaction between Akkermansia muciniphila and the butyrogenic gut commensal Anaerostipes caccae using a metatranscriptomic approach. Antonie van Leeuwenhoek, 2018, 111(6):859-873.
    [34] Chen L, Chen R, Wang H, Liang FX. Mechanisms linking inflammation to insulin resistance. International Journal of Endocrinology, 2015, 2015:508409.
    [35] Cani PD, Amar J, Iglesias MA, Poggi M, Knauf C, Bastelica D, Neyrinck AM, Fava F, Tuohy KM, Chabo C, Waget A, Delmée E, Cousin B, Sulpice T, Chamontin B, Ferrières J, Tanti JF, Gibson GR, Casteilla L, Delzenne NM, Alessi MC, Burcelin R. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes, 2007, 56(7):1761-1772.
    [36] Shi H, Kokoeva MV, Inouye K, Tzameli I, Yin HL, Flier JS. TLR4 links innate immunity and fatty acid-induced insulin resistance. Journal of Clinical Investigation, 2006, 116(11):3015-3025.
    [37] Zhao SQ, Liu W, Wang JQ, Shi J, Sun YK, Wang WQ, Ning G, Liu RX, Hong J. Akkermansia muciniphila improves metabolic profiles by reducing inflammation in chow diet-fed mice. Journal of Molecular Endocrinology, 2017, 58(1):1-14.
    [38] Zhang L, Qin QQ, Liu MN, Zhang XL, He F, Wang GQ. Akkermansia muciniphila can reduce the damage of gluco/lipotoxicity, oxidative stress and inflammation, and normalize intestine microbiota in streptozotocin-induced diabetic rats. Pathogens and Disease, 2018, 76(4):fty028.
    [39] van der Lugt B, van Beek AA, Aalvink S, Meijer B, Sovran B, Vermeij WP, Brandt RMC, de Vos WM, Savelkoul HFJ, Steegenga WT, Belzer C. Akkermansia muciniphila ameliorates the age-related decline in colonic mucus thickness and attenuates immune activation in accelerated aging Ercc1-/Δ7 mice. Immunity & Ageing, 2019, 16:6.
    [40] Ashrafian F, Behrouzi A, Shahriary A, Ahmadi Badi S, Davari M, Khatami S, Rahimi Jamnani FR, Fateh A, Vaziri F, Siadat SD. Comparative study of effect of Akkermansia muciniphila and its extracellular vesicles on toll-like receptors and tight junction. Gastroenterology and Hepatology from Bed to Bench, 2019, 12(2):163-168.
    [41] Depommier C, Everard A, Druart C, Plovier H, van Hul M, Vieira-Silva S, Falony G, Raes J, Maiter D, Delzenne NM, de Barsy M, Loumaye A, Hermans MP, Thissen JP, de Vos WM, Cani PD. Supplementation with Akkermansia muciniphila in overweight and obese human volunteers:a proof-of-concept exploratory study. Nature Medicine, 2019, 25(7):1096-1103.
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Xinyan Dong, Xue Liu, Manni Liu, Xiangling Zhang, Guoqing Wang. Role of Akkermansia muciniphila in diabetes and obesity. [J]. Acta Microbiologica Sinica, 2020, 60(5): 856-863

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History
  • Received:September 09,2019
  • Revised:October 29,2019
  • Online: May 11,2020
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