肠道微生物与人类疾病关系的研究进展

doi:10.3969/j.issn.1673-8640.2017.12.022

摘要/Abstract

摘要：

肠道微生物是寄居于人体肠道的庞大群落,其像是一个器官,具备代谢、免疫和内分泌等多种生理功能,并与人体的其他器官相互作用。在遗传、饮食等外界因素影响下,肠道微生物菌群失调或与人体的平衡被打破,就会导致多种疾病。文章主要从肠道微生物与代谢综合征、心血管疾病、癌症、类风湿性关节炎（RA）以及中枢神经系统疾病的关系进行综述。

关键词: 肠道微生物, 人类疾病, 代谢, 炎症, 菌群失调

Abstract:

Human intestine harbors a large amount of microorganisms（gut microbiome）,which works like an organ providing metabolic,immunologic and enter-endocrinal physiological functions and develops commensal relationships with human organism. Under the influence of genetic factors,dietary habits and so on,if the dysbiosis of gut microflora occurs,or the balance with human organism is broken, it would lead to many kinds of diseases. This review mainly shows the relationships between gut microbiome and metabolic syndrome,cardiovascular disease,cancer,rheumatoid arthritis and central nerve system diseases.

Key words: Gut microbiome, Human diseases, Metabolism, Inflammation, Gut microflora dysbiosis

中图分类号:

R446.5

郭晗, 张捷, 杨硕, 乔蕊. 肠道微生物与人类疾病关系的研究进展[J]. 检验医学, 2017, 32(12): 1165-1172.

GUO Han, ZHANG Jie, YANG Shuo, QIAO Rui. Research progress in the relationship between gut microbiome and human diseases[J]. Laboratory Medicine, 2017, 32(12): 1165-1172.

参考文献 48

[1]	HOOPER L V,GORDON J I.Commensal host-bacterial relationships in the gut[J]. Science,2001,292(5519):1115-1118.
[2]	D'ARGENIO V,SALVATORE F. The role of the gut microbiome in the healthy adult status[J]. Clin Chim Acta,2015,451(Pt A):97-102.
[3]	PALMER C,BIK E M,DIGIULIO D B,et al.Development of the human infant intestinal microbiota[J]. PLoS Biol,2007,5(7):e177.
[4]	KOENIG J E,SPOR A,SCALFONE N,et al.Succession of microbial consortia in the developing infant gut microbiome[J]. Proc Natl Acad Sci U S A,2011,108(Suppl 1):4578-4585.
[5]	BÄCKHED F,ROSWALL J,PENG Y,et al. Dynamics and stabilization of the human gut microbiome during the first year of life[J]. Cell Host Microbe,2015,17(5):690-703.
[6]	MARIAT D,FIRMESSE O,LEVENEZ F,et al.The Firmicutes/Bacteroidetes ratio of the human microbiota changes with age[J]. BMC Microbiol,2009,9:123.
[7]	SUZUKI T A,WOROBEY M.Geographical variation of human gut microbial composition[J]. Biol Lett,2014,10(2):20131037.
[8]	YATSUNENKO T,REY F E,MANARY M J,et al.Human gut microbiome viewed across age and geography[J]. Nature,2012,486(7402):222-227.
[9]	DETHLEFSEN L,RELMAN D A.Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation[J]. Proc Natl Acad Sci U S A,2011,108(Suppl 1):4554-4561.
[10]	ZHANG C,ZHANG M,WANG S,et al.Interactions between gut microbiota,host genetics and diet relevant to development of metabolic syndromes in mice[J]. ISME J,2010,4(2):232-241.
[11]	LOZUPONE C A,STOMBAUGH J I,GORDON J I,et al.Diversity,stability and resilience of the human gut microbiota[J]. Nature,2012,489(7415):220-230.
[12]	CLAESSON M J,CUSACK S,O'SULLIVAN O,et al. Composition,variability,and temporal stability of the intestinal microbiota of the elderly[J]. Proc Natl Acad Sci U S A,2011,108(Suppl 1):4586-4591.
[13]	ZOETENDAL E G,RAES J,VAN DEN BOGERT B,et al. The human small intestinal microbiota is driven by rapid uptake and conversion of simple carbohydrates[J]. ISME J,2012,6(7):1415-1426.
[14]	BIK E M,ECKBURG P B,GILL S R,et al.Molecular analysis of the bacterial microbiota in the human stomach[J]. Proc Natl Acad Sci U S A,2006,103(3):732-737.
[15]	FRANZOSA E A,HUANG K,MEADOW J F,et al.Identifying personal microbiomes using metagenomic codes[J]. Proc Natl Acad Sci U S A,2015,112(22):E2930-E2938.
[16]	ECKBURG P B,BIK E M,BERNSTEIN C N,et al.Diversity of the human intestinal microbial flora[J]. Science,2005,308(5728):1635-1638.
[17]	QIN J,LI R,RAES J,et al.A human gut microbial gene catalogue established by metagenomic sequencing[J]. Nature,2010,464(7285):59-65.
[18]	MATSUKI T,WATANABE K,FUJIMOTO J,et al.Use of 16S rRNA gene-targeted group-specific primers for real-time PCR analysis of predominant bacteria in human feces[J]. Appl Environ Microbiol,2004,70(12):7220-7228.
[19]	FRANKS A H,HARMSEN H J,RAANGS G C,et al.Variations of bacterial populations in human feces measured by fluorescent in situ hybridization with group-specific 16S rRNA-targeted oligonucleotide probes[J]. Appl Environ Microbiol,1998,64(9):3336-3345.
[20]	VIJAY-KUMAR M,AITKEN J D,CARVALHO F A,et al.Metabolic syndrome and altered gut microbiota in mice lacking Toll-like receptor 5[J]. Science,2010,328(5975):228-231.
[21]	ZHANG W,HARTMANN R,TUN H M,et al.Deletion of the Toll-like receptor 5 gene per se does not determine the gut microbiome profile that induces metabolic syndrome:environment trumps genotype[J]. PLoS One,2016,11(3):e0150943.
[22]	BÄCKHED F,MANCHESTER J K,SEMENKOVICH C F,et al. Mechanisms underlying the resistance to diet-induced obesity in germ-free mice[J]. Proc Natl Acad Sci U S A,2007,104(3):979-984.
[23]	ALANG N,KELLY C R. Weight gain after fecal microbiota transplantation[J]. Open Forum Infect Dis,2015,2(1):ofv004.
[24]	LEY R E,TURNBAUGH P J,KLEIN S,et al.Microbial ecology:human gut microbes associated with obesity[J]. Nature,2006,444(7122):1022-1023.
[25]	LE CHATELIER E,NIELSEN T,QIN J,et al.Richness of human gut microbiome correlates with metabolic markers[J]. Nature,2013,500(7464):541-546.
[26]	BOULANGE C L,NEVES A L,CHILLOUX J,et al.Impact of the gut microbiota on inflammation,obesity,and metabolic disease[J]. Genome Med,2016,8(1):42.
[27]	FAK F,TREMAROLI V,BERGSTRÖM G,et al. Oral microbiota in patients with atherosclerosis[J]. Atherosclerosis,2015,243(2):573-578.
[28]	KARLSSON F H,FAK F,NOOKAEW I,et al.Symptomatic atherosclerosis is associated with an altered gut metagenome[J]. Nat Commun,2012,3:1245.
[29]	PASINI E,AQUILANI R,TESTA C,et al.Pathogenic gut flora in patients with chronic heart failure[J]. JACC Heart Fail,2016,4(3):220-227.
[30]	WANG Z,KLIPFELL E,BENNETT B J,et al.Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease[J]. Nature,2011,472(7341):57-63.
[31]	KOETH R A,WANG Z,LEVISON B S,et al.Intestinal microbiota metabolism of L-carnitine,a nutrient in red meat,promotes atherosclerosis[J]. Nat Med,2013,19(5):576-585.
[32]	SELDIN M M,MENG Y,QI H,et al. Trimethylamine N-oxide promotes vascular inflammation through signaling of mitogen-activated protein kinase and nuclear factor-κB[J]. J Am Heart Assoc,2016,5(2):pii.e002767.
[33]	ZHU W,GREGORY J C,ORG E,et al.Gut microbial metabolite TMAO enhances platelet hyperreactivity and thrombosis risk[J]. Cell,2016,165(1):111-124.
[34]	ZITVOGEL L,GALLUZZI L,VIAUD S,et al. Cancer and the gut microbiota:an unexpected link[J]. Sci Transl Med,2015,7(271):271ps1.
[35]	LOUIS P,HOLD G L,FLINT H J.The gut microbiota,bacterial metabolites and colorectal cancer[J]. Nat Rev Microbiol,2014,12(10):661-672.
[36]	BONNET M,BUC E,SAUVANET P,et al.Colonization of the human gut by E. coli and colorectal cancer risk[J]. Clin Cancer Res,2014,20(4):859-867.
[37]	YANG J,TAN Q,FU Q,et al.Gastrointestinal microbiome and breast cancer:correlations,mechanisms and potential clinical implications[J]. Breast Cancer,2017,24(2):220-228.
[38]	TANEJA V.Arthritis susceptibility and the gut microbiome[J]. FEBS Lett,2014,588(22):4244-4249.
[39]	SCHER J U,SCZESNAK A,LONGMAN R S,et al.Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis[J]. Elife,2013,2:e01202.
[40]	CHEN J,WRIGHT K,DAVIS J M,et al.An expansion of rare lineage intestinal microbes characterizes rheumatoid arthritis[J]. Genome Med, 2016,8(1):43.
[41]	MARIETTA E V,MURRAY J A,LUCKEY D H,et al.Suppression of inflammatory arthritis by human gut-derived Prevotella histicola in humanized mice[J]. Arthritis Rheumatol, 2016, 68(12):2878-2888.
[42]	OCHOA-REPARAZ J,KASPER L H.The second brain:is the gut microbiota a link between obesity and central nervous system disorders?[J]. Curr Obes Rep,2016,5(1):51-64.
[43]	CRUMEYROLLE-ARIAS M,JAGLIN M,BRUNEAU A,et al.Absence of the gut microbiota enhances anxiety-like behavior and neuroendocrine response to acute stress in rats[J]. Psychoneuroendocrinology,2014,42:207-217.
[44]	COURY D L,ASHWOOD P,FASANO A,et al.Gastrointestinal conditions in children with autism spectrum disorder:developing a research agenda[J]. Pediatrics,2012,130(Suppl 2):S160-S168.
[45]	KANG D W,PARK J G,ILHAN Z E,et al.Reduced incidence of Prevotella and other fermenters in intestinal microflora of autistic children[J]. PLoS One,2013,8(7):e68322.
[46]	HSIAO E Y,MCBRIDE S W,HSIEN S,et al.Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders[J]. Cell,2013,155(7):1451-1463.
[47]	FASANO A,VISANJI N P,LIU L W,et al.Gastrointestinal dysfunction in Parkinson's disease[J]. Lancet Neurol,2015,14(6):625-639.
[48]	KESHAVARZIAN A,GREEN S J,ENGEN P A,et al.Colonic bacterial composition in Parkinson's disease[J]. Mov Disord,2015,30(10):1351-1360.