肠道中Akkermansia muciniphila数量影响因素的研究进展
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摘要
Akkermansia muciniphila (AKK菌)是在人体粪便样品中分离的一种细菌,也是目前唯一可培养的疣微菌门肠道微生物。因它在黏蛋白降解过程中的特殊性能而成为肠腔与宿主细胞间黏膜界面的关键生物,和炎症性肠病、肥胖、酒精肝、孤独症、结肠炎、2型糖尿病、1型糖尿病及其他代谢紊乱等密切相关。作为宿主肠道微生物的一员,AKK菌的数量必然受到体内、体外多种因素的影响,其中,饮食、抗生素及其他药物、益生菌和益生元、天然产物、温度、体内免疫蛋白等均是目前已知的影响因素。这篇文章从AKK菌的生理特性、与宿主的关系及其数量的影响因素等3个方面对现有研究进行综述。
Akkermansia muciniphila(AKK),the only cultivatable intestinal representative of the Verrucomicrobia,is an intestinal bacterium that was isolated from a human fecal sample.Its special property in mucin degradation makes it a key organism at the mucosal interface between the lumen and host cells,and it is closely related to inflammatory bowel disease,obesity,alcoholic liver,autism,colitis,type 2 diabetes,type 1 diabetes and other metabolic disorders.As one of intestinal microbes of the?host,the number of AKK is affected by many factors in vivo and in vitro,including diet,antibiotics and other medicines,probiotics and prebiotics,other natural products,temperature and immune receptor,all of which are known affecting factors at present.The aims of this review are to summarize the current research on AKK,including three aspects,AKK physiological characteristics,the relationship between AKK and their hosts,and the influencing factors of AKK quantity.
Akkermansia muciniphila(AKK),the only cultivatable intestinal representative of the Verrucomicrobia,is an intestinal bacterium that was isolated from a human fecal sample.Its special property in mucin degradation makes it a key organism at the mucosal interface between the lumen and host cells,and it is closely related to inflammatory bowel disease,obesity,alcoholic liver,autism,colitis,type 2 diabetes,type 1 diabetes and other metabolic disorders.As one of intestinal microbes of the?host,the number of AKK is affected by many factors in vivo and in vitro,including diet,antibiotics and other medicines,probiotics and prebiotics,other natural products,temperature and immune receptor,all of which are known affecting factors at present.The aims of this review are to summarize the current research on AKK,including three aspects,AKK physiological characteristics,the relationship between AKK and their hosts,and the influencing factors of AKK quantity.
引文
[1]Ouwerkerk JP,de Vos WM,Belzer C.Glycobiome:Bacteria and mucus at the epithelial interface[J].Best Prac Res Clin Gastroenterol,2013,27(1):25-38.
[2]Rajilic′-Stojanovic′M,de Vos WM.The first 1000cultured species of the human gastrointestinal microbiota[J].FEMS Microbiol Rev,2014,38(5):996-1047.
[3]Derrien M,Belzer C,de Vos WM,et al.Akkermansia muciniphila and its role in regulating host functions[J].Microb Pathog,2017,106:171-181.
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[6]Guo X,Zhang J,Wu F,et al.Different subtype strains of Akkermansia muciniphila abundantly colonize in southern China[J].J Appl Microb,2016,120(2):452-459.
[7]FENG Zemeng,BAO Xianying,YIN Yulong.The interaction of colonization of Akkermansia muciniphilain gastrointestinal tract and its host[J].Sci Agric Sin,2016,49(8):1577-1584.(in Chinese)冯泽猛,包显颖,印遇龙.胃肠道黏液层中Akkermansia muciniphila的定殖及其与宿主的相互作用[J].中国农业科学,2016,49(8):1577-1584.
[8]Derrien M,Vaughan EE,Plugge CM,et al.Akkermansia muciniphila gen.nov.,sp.nov.,a human intestinal mucin-degrading bacterium[J].Int J Syst Evol Microbiol,2004,54(Pt5):1469-1476.
[9]Kathrin F.Mechanisms of Bacterial Uncultivability in the human gut microbiome[D].Boston:Northeastern University,2014.
[10]HUANG Kun.Gene cloning,expression and enzymatic characterization of sialidases isolated fromAkkermansia muciniphila[D].Nanjing:Nanjing Agricultural University,2015.(in Chinese)黄坤.Akkermansia muciniphila源唾液酸糖苷酶基因的克隆表达与酶学特性硏究[D].南京:南京农业大学,2015.
[11]Huang K,Wang MM,Kulinich A,et al.Biochemical characterisation of the neuraminidase pool of the human gut symbiont Akkermansia muciniphila[J].Carbohyd Res,2015,415:60-65.
[12]Caputo A,Dubourg G,Croce O,et al.Whole-genome assembly of Akkermansia muciniphila sequenced directly from human stool[J].Biol Direct,2015,10:5.
[13]Karlsson CL,Onnerflt 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.
[14]Ye JX.Intestinal bacteria associated with colitis and inflammatory bowel disease[D].Riverside:University of California Riverside,2009.
[15]Wang L,Christophersen CT,Sorich MJ,et al.Low relative abundances of the mucolytic bacterium Akkermansia muciniphila and Bifidobacteriumspp.in faces of children with autism[J].Appl Environ Microbiol,2011,77(18):6718-6721.
[16]Cani PD,Geurts L,Matamoros S,et al.Glucose metabolism:Focus on gut microbiota,the endocannabinoid system and beyond[J].Diabetes Metab,2014,40(4):246-257.
[17]Everard A,Belzer C,Geurts L,et al.Cross-talk between Akkermansia muciniphila and intestinal epithelium controls dietinduced obesity[J].Proc Natl Acad Sci U S A,2013,110(22):9066-9071.
[18]Seregin SS,Golovchenko N,Schaf B,et al.NLRP6protects Il10-/-mice from colitis by limiting colonization of Akkermansia muciniphila[J].Cell Rep,2017,19(4):733-745.
[19]Neyrinck AM,Etxeberria U,Taminiau B,et al.Rhubarb extract prevents hepatic inflammation induced by acute alcohol intake,an effect related to the modulation of the gut microbiota[J].Mol Nutr Food Res,2017,61(1).doi:10.1002/mnfr.201500899.
[20]Everard A,Belzer C,Geurts L,et al.Akkermansia muciniphila communique avec l′épithélium intestinal pour contr8ler le développement de l′obésitéet du diabète de type 2[J].Diabetes Metabol,2013,39(1):A19.
[21]Hansen CH,Krych L,Nielsen DS,et al.Early life treatment with vancomycin propagates Akkermansia muciniphila and reduces diabetes incidence in the NOD mouse[J].Diabetologia,2012,55(8):2285-2294.
[22]Dingemanse C,Belzer C,van Hijum SA,et al.Akkermansia muciniphila and Helicobacter typhlonius modulate intestinal tumor development in mice[J].Carcinogenesis,2015,36(11):1388-1396.
[23]Underwood MA.Intestinal dysbiosis:Novel mechanisms by which gut microbes trigger and prevent disease[J].Prev Med,2014,65:133-137.
[24]GAO Jie,SUN Jing,HUANG Jian,et al.Regulation effects of kefir on gut microbiota in high fat diet fed hamster[J].China Brew,2017,36(4):15-19.(in Chinese)高洁,孙静,黄建,等.开菲尔对高脂金黄地鼠肠道菌群的调节作用研究[J].中国酿造,2017,36(4):15-19.
[25]GAO Xiaoyu.Gut microbiota mediates the protective effects of post fermented Pu-er tea against diet-induced metabolic syndrome[D].Changchun:Jilin University,2017.(in Chinese)高晓余.肠道菌群介导的后发酵普洱茶改善饮食诱导的代谢综合症[D].长春:吉林大学,2017.
[26]Sonoyama K,Ogasawara T,Goto H,et al.Comparison of gut microbiota and allergic reactions in BALB/c mice fed different cultivars of rice[J].Br J Nutr,2010,103(2):218-226.
[27]Christine TP.The structure and function of the murine gut microbiome in sub-therapeutic antibiotic induced obesity[D].Washington:George Washington University,2014.
[28]Dubourg G,Lagier JC,Armougom F,et al.High-level colonisation of the human gut by Verrucomicrobia following broadspectrum antibiotic treatment[J].In J Antimicrob Agents,2013,41(2):149-155.
[29]Hansen CH,Holm TL,Krych,et al.Gut microbiota regulates NKG2Dligand expression on intestinal epithelial cells[J].Eur J Immunol,2013,43(2):447-457.
[30]Shin NR,Lee JC,Lee HY,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.
[31]Lee H,Ko G.Effect of metformin on metabolic Improvement and gut microbiota[J].Appl Environ Microb,2014,80(19):5935-5943.
[32]Sands SA,Tsau S,Yankee TM,et al.The effect of omeprazole on the development of experimental autoimmune encephalomyelitis in C57BL/6Jand SJL/J mice[J].BMC Res Notes,2014,7:605.
[33]Etxeberria U,Hijona E,Aguirre L,et al.Pterostilbene-induced changes in gut microbiota composition in relation to obesity[J].Mol Nutr Food Res,2017,61(1).doi:10.1002/mnfr.201500906.
[34]TI Panpan,WANG Jianming,PANG Xiaoyang,et al.Effects of Lactobacillus casei SY13and its symbiotic on the abundance of Akkermansia muciniphila in mice intestine tract[J].Sci Technol Food Industry,2018,39(10):308-314.(in Chinese)提盼盼,汪建明,逄晓阳,等.干酪乳杆菌SY13及其合生元对小鼠肠道中Akkermansia muciniphila丰度的影响[J].食品工业科技,2018,39(10):308-314.
[35]Van den Abbeele P,Gérard P,Rabot S,et al.Arabinoxylans and inulin differentially modulate the mucosal and luminal gut microbiota and mucin-degradation in humanized rats[J].Environ Microbiol,2011,13(10):2667-2680.
[36]Power KA,Lepp D,Zarepoor L,et al.Dietary flaxseed modulates the colonic microenvironment in healthy C57Bl/6 male mice which may alter susceptibility to gut-associated diseases[J].J Nutr Biochem,2016,28:61-69.
[37]Shang QS,Song GR,Zhang MF,et al.Dietary fucoidan improves metabolic syndrome in association with increased Akkermansia population in the gut microbiota of high-fat diet-fed mice[J].J Funct Foods,2017,28:138-146.
[38]Henning SM,Summanen PH,Lee RP,et al.Pomegranate ellagitannins stimulate the growth of Akkermansia muciniphila in vivo[J].Anaerobe,2017,43:56-60.
[39]Li Z,Henning SM,Lee RP,et al.Pomegranate extract induces ellagitannin metabolite formation and changes stool microbiota in healthy volunteers[J].Food Funct,2015,6(8),2487-2495.
[40]Chevalier C,Stojanovic′O,Colin DJ,et al.Gut microbiota orchestrates energy homeostasis during cold[J].Cell,2015,163(6):1360-1374.
[41]Rob TB,Rolf B,Eline SK,et al.Microbial functionality in the human gastrointestinal tract[J].Microbes Environ,2004,19(4):276-280.
[42]Belzer C,de Vos WM.Microbes inside-from diversity to function:The case of Akkermansia[J].ISME J,2012,6(8):1449-1458.收稿日期修回日期本文编辑
[2]Rajilic′-Stojanovic′M,de Vos WM.The first 1000cultured species of the human gastrointestinal microbiota[J].FEMS Microbiol Rev,2014,38(5):996-1047.
[3]Derrien M,Belzer C,de Vos WM,et al.Akkermansia muciniphila and its role in regulating host functions[J].Microb Pathog,2017,106:171-181.
[4]GAO Kan,WANG Xuefeng,ZHANG Wenming,et al.Function of intestinal epithelial barriers modulated by probiotics and mechanisms[J].Chin J Anim Nutr,2013,25(9):1936-1945.(in Chinese)高侃,汪学峰,章文明,等.益生菌调节肠道上皮屏障功能及作用机制[J].动物营养学报,2013,25(9):1936-1945.
[5]ZHAO Fan,LI Chunbao.Characteristics of intestinal bacterium Akkermansia muciniphila and the association with host health[J].Microbiol China,2017,44(6):1458-1463.(in Chinese)赵凡,李春保.肠道菌Akkermansia muciniphila的特性及其与机体健康的关系[J].微生物学通报,2017,44(6):1458-1463.
[6]Guo X,Zhang J,Wu F,et al.Different subtype strains of Akkermansia muciniphila abundantly colonize in southern China[J].J Appl Microb,2016,120(2):452-459.
[7]FENG Zemeng,BAO Xianying,YIN Yulong.The interaction of colonization of Akkermansia muciniphilain gastrointestinal tract and its host[J].Sci Agric Sin,2016,49(8):1577-1584.(in Chinese)冯泽猛,包显颖,印遇龙.胃肠道黏液层中Akkermansia muciniphila的定殖及其与宿主的相互作用[J].中国农业科学,2016,49(8):1577-1584.
[8]Derrien M,Vaughan EE,Plugge CM,et al.Akkermansia muciniphila gen.nov.,sp.nov.,a human intestinal mucin-degrading bacterium[J].Int J Syst Evol Microbiol,2004,54(Pt5):1469-1476.
[9]Kathrin F.Mechanisms of Bacterial Uncultivability in the human gut microbiome[D].Boston:Northeastern University,2014.
[10]HUANG Kun.Gene cloning,expression and enzymatic characterization of sialidases isolated fromAkkermansia muciniphila[D].Nanjing:Nanjing Agricultural University,2015.(in Chinese)黄坤.Akkermansia muciniphila源唾液酸糖苷酶基因的克隆表达与酶学特性硏究[D].南京:南京农业大学,2015.
[11]Huang K,Wang MM,Kulinich A,et al.Biochemical characterisation of the neuraminidase pool of the human gut symbiont Akkermansia muciniphila[J].Carbohyd Res,2015,415:60-65.
[12]Caputo A,Dubourg G,Croce O,et al.Whole-genome assembly of Akkermansia muciniphila sequenced directly from human stool[J].Biol Direct,2015,10:5.
[13]Karlsson CL,Onnerflt 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.
[14]Ye JX.Intestinal bacteria associated with colitis and inflammatory bowel disease[D].Riverside:University of California Riverside,2009.
[15]Wang L,Christophersen CT,Sorich MJ,et al.Low relative abundances of the mucolytic bacterium Akkermansia muciniphila and Bifidobacteriumspp.in faces of children with autism[J].Appl Environ Microbiol,2011,77(18):6718-6721.
[16]Cani PD,Geurts L,Matamoros S,et al.Glucose metabolism:Focus on gut microbiota,the endocannabinoid system and beyond[J].Diabetes Metab,2014,40(4):246-257.
[17]Everard A,Belzer C,Geurts L,et al.Cross-talk between Akkermansia muciniphila and intestinal epithelium controls dietinduced obesity[J].Proc Natl Acad Sci U S A,2013,110(22):9066-9071.
[18]Seregin SS,Golovchenko N,Schaf B,et al.NLRP6protects Il10-/-mice from colitis by limiting colonization of Akkermansia muciniphila[J].Cell Rep,2017,19(4):733-745.
[19]Neyrinck AM,Etxeberria U,Taminiau B,et al.Rhubarb extract prevents hepatic inflammation induced by acute alcohol intake,an effect related to the modulation of the gut microbiota[J].Mol Nutr Food Res,2017,61(1).doi:10.1002/mnfr.201500899.
[20]Everard A,Belzer C,Geurts L,et al.Akkermansia muciniphila communique avec l′épithélium intestinal pour contr8ler le développement de l′obésitéet du diabète de type 2[J].Diabetes Metabol,2013,39(1):A19.
[21]Hansen CH,Krych L,Nielsen DS,et al.Early life treatment with vancomycin propagates Akkermansia muciniphila and reduces diabetes incidence in the NOD mouse[J].Diabetologia,2012,55(8):2285-2294.
[22]Dingemanse C,Belzer C,van Hijum SA,et al.Akkermansia muciniphila and Helicobacter typhlonius modulate intestinal tumor development in mice[J].Carcinogenesis,2015,36(11):1388-1396.
[23]Underwood MA.Intestinal dysbiosis:Novel mechanisms by which gut microbes trigger and prevent disease[J].Prev Med,2014,65:133-137.
[24]GAO Jie,SUN Jing,HUANG Jian,et al.Regulation effects of kefir on gut microbiota in high fat diet fed hamster[J].China Brew,2017,36(4):15-19.(in Chinese)高洁,孙静,黄建,等.开菲尔对高脂金黄地鼠肠道菌群的调节作用研究[J].中国酿造,2017,36(4):15-19.
[25]GAO Xiaoyu.Gut microbiota mediates the protective effects of post fermented Pu-er tea against diet-induced metabolic syndrome[D].Changchun:Jilin University,2017.(in Chinese)高晓余.肠道菌群介导的后发酵普洱茶改善饮食诱导的代谢综合症[D].长春:吉林大学,2017.
[26]Sonoyama K,Ogasawara T,Goto H,et al.Comparison of gut microbiota and allergic reactions in BALB/c mice fed different cultivars of rice[J].Br J Nutr,2010,103(2):218-226.
[27]Christine TP.The structure and function of the murine gut microbiome in sub-therapeutic antibiotic induced obesity[D].Washington:George Washington University,2014.
[28]Dubourg G,Lagier JC,Armougom F,et al.High-level colonisation of the human gut by Verrucomicrobia following broadspectrum antibiotic treatment[J].In J Antimicrob Agents,2013,41(2):149-155.
[29]Hansen CH,Holm TL,Krych,et al.Gut microbiota regulates NKG2Dligand expression on intestinal epithelial cells[J].Eur J Immunol,2013,43(2):447-457.
[30]Shin NR,Lee JC,Lee HY,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.
[31]Lee H,Ko G.Effect of metformin on metabolic Improvement and gut microbiota[J].Appl Environ Microb,2014,80(19):5935-5943.
[32]Sands SA,Tsau S,Yankee TM,et al.The effect of omeprazole on the development of experimental autoimmune encephalomyelitis in C57BL/6Jand SJL/J mice[J].BMC Res Notes,2014,7:605.
[33]Etxeberria U,Hijona E,Aguirre L,et al.Pterostilbene-induced changes in gut microbiota composition in relation to obesity[J].Mol Nutr Food Res,2017,61(1).doi:10.1002/mnfr.201500906.
[34]TI Panpan,WANG Jianming,PANG Xiaoyang,et al.Effects of Lactobacillus casei SY13and its symbiotic on the abundance of Akkermansia muciniphila in mice intestine tract[J].Sci Technol Food Industry,2018,39(10):308-314.(in Chinese)提盼盼,汪建明,逄晓阳,等.干酪乳杆菌SY13及其合生元对小鼠肠道中Akkermansia muciniphila丰度的影响[J].食品工业科技,2018,39(10):308-314.
[35]Van den Abbeele P,Gérard P,Rabot S,et al.Arabinoxylans and inulin differentially modulate the mucosal and luminal gut microbiota and mucin-degradation in humanized rats[J].Environ Microbiol,2011,13(10):2667-2680.
[36]Power KA,Lepp D,Zarepoor L,et al.Dietary flaxseed modulates the colonic microenvironment in healthy C57Bl/6 male mice which may alter susceptibility to gut-associated diseases[J].J Nutr Biochem,2016,28:61-69.
[37]Shang QS,Song GR,Zhang MF,et al.Dietary fucoidan improves metabolic syndrome in association with increased Akkermansia population in the gut microbiota of high-fat diet-fed mice[J].J Funct Foods,2017,28:138-146.
[38]Henning SM,Summanen PH,Lee RP,et al.Pomegranate ellagitannins stimulate the growth of Akkermansia muciniphila in vivo[J].Anaerobe,2017,43:56-60.
[39]Li Z,Henning SM,Lee RP,et al.Pomegranate extract induces ellagitannin metabolite formation and changes stool microbiota in healthy volunteers[J].Food Funct,2015,6(8),2487-2495.
[40]Chevalier C,Stojanovic′O,Colin DJ,et al.Gut microbiota orchestrates energy homeostasis during cold[J].Cell,2015,163(6):1360-1374.
[41]Rob TB,Rolf B,Eline SK,et al.Microbial functionality in the human gastrointestinal tract[J].Microbes Environ,2004,19(4):276-280.
[42]Belzer C,de Vos WM.Microbes inside-from diversity to function:The case of Akkermansia[J].ISME J,2012,6(8):1449-1458.收稿日期修回日期本文编辑