论共生系统:肠道菌群和人类健康
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摘要
共生是生物界中普遍存在的一种现象,互利共生的一个典型例子就是人类和肠道菌群.人类利用肠道菌群消化食物来获得生存所需的能量和营养,而肠道菌群则获得栖息地和营养.肠道菌群与人类相互作用形成了一种与人类健康密切相关的平衡状态,打破这种平衡状态会导致人体内的许多疾病,如肥胖、高血压、炎症性肠病、癌症等.肠道菌群参与宿主新陈代谢、机体免疫、基因表达、疾病发展和药物疗效,同时它也受饮食、抗生素、生活方式、遗传和时间点的影响.作者系统地回顾了人类与肠道菌群之间的相互作用,分析了肠道菌群在人类疾病治疗中的应用现状,描述了治疗中存在的主要问题,为肠道菌群在人类疾病治疗中的应用提供了新的思路.
Symbiosis is a ubiquitous phenomenon in the biological world.A typical example of mutualism is human and gut microbiota.Humans use the gut microbiota to consume food to get the energy and nutrients necessary for survival,while the gut microbiota gains habitat and nutritions.Gut microbiota interacts with humans to form a balance state that is closely related to human health,and the disequilibrium can result in many diseases in human such as obesity,high blood pressure,inflammatory bowel disease,cancer and so on.The gut microbiota participates in host metabolism,organism immunity,gene expression,disease development and drug efficacy,while it is also affected by diet,antibiotics,lifestyle,inheritance and time.The authors systernatically reviewed the interaction between human and gut microbiota,analyzed the application status of the gut microbiota in the treatment of human diseases,described the main problems in the treatment and provided new ideas for the application of gut microbiota in the treatment of human diseases.
Symbiosis is a ubiquitous phenomenon in the biological world.A typical example of mutualism is human and gut microbiota.Humans use the gut microbiota to consume food to get the energy and nutrients necessary for survival,while the gut microbiota gains habitat and nutritions.Gut microbiota interacts with humans to form a balance state that is closely related to human health,and the disequilibrium can result in many diseases in human such as obesity,high blood pressure,inflammatory bowel disease,cancer and so on.The gut microbiota participates in host metabolism,organism immunity,gene expression,disease development and drug efficacy,while it is also affected by diet,antibiotics,lifestyle,inheritance and time.The authors systernatically reviewed the interaction between human and gut microbiota,analyzed the application status of the gut microbiota in the treatment of human diseases,described the main problems in the treatment and provided new ideas for the application of gut microbiota in the treatment of human diseases.
引文
[1]RUTTEN N B,GORISSEN D M,ECK A,et al.Long term development of gut microbiota composition in atopic children:Impact of probiotics[J].PLoS One,2015,10(9):e0137681.
[2]GROER M W,LUCIANO A A,DISHAW L J,et al.Development of the preterm infant gut microbiome:A research priority[J].Microbiome,2014,2:38.
[3]FRESE S A,PARKER K,CALVERT C C,et al.Diet shapes the gut microbiome of pigs during nursing and weaning[J].Microbiome,2015,3:28.
[4]KOVATCHEVA-DATCHARY P,NILSSON A,AKRAMI R,et al.Dietary fiber-induced improvement in glucose metabolism is associated with increased abundance of Prevotella[J].Cell Metabolism,2015,22:971-982.
[5]EID N,ENANI S,WALTON G,et al.The impact of date palm fruits and their component polyphenols,on gut microbial ecology,bacterial metabolites and colon cancer cell proliferation[J].International Journal of Food Sciences and Nutrition,2014,3:e46.
[6]BAI G,TSURUTA T,NISHINO N.Dietary soy,meat,and fish proteins modulate the effects of prebiotic raffinose on composition an fermentation of gut microbiota in rats[J].International Journal of Food Sciences and Nutrition,2018,69(4):480-487.
[7]DAVID L A,MAURICE C F,CARMODY R N,et al.Diet rapidly and reproducibly alters the human gut microbiome[J].Nature,2014,505:559-563.
[8]CAESAR R,TREMAROLI V,KOVATCHEVA-DATCHARY P,et al.Crosstalk between gut microbiota and dietary lipids aggravates WAT inflammation through TLR signaling[J].Cell Metabolism,2015,22:658-668.
[9]CUERVO A,HEVIA A,LPEZ P,et al.Phenolic compounds from red wine and coffee are associated with specific intestinal microorganisms in allergic subjects[J].Food Function,2015,7(1):104-109.
[10]COTILLARD A,KENNEDY S P,KONG L C,et al.Dietary intervention impact on gut microbial gene richness[J].Nature,2013,500:585-588.
[11]ETXEBERRIA U,FERNNDEZQUINTELA A,MILAGRO F I,et al.Impact of polyphenols and polyphenol-rich dietary sources on gut microbiota composition[J].Journal of Agricultural&Food Chemistry,2013,61(40):9517-9533.
[12]WILCK N,MATUS M G,KEARNEY S M,et al.Salt-responsive gut commensal modulates TH17axis and disease[J].Nature,2017,551(7682):585-589.
[13]DE A M,MONTEMURNO E,VANNINI L,et al.Effect of whole-grain barley on the human fecal microbiota and metabolome[J].Applied&Environmental Microbiology,2015,81(22):7945-7956.
[14]NAKATA T,KYOUI D,TAKAHASHI H,et al.Inhibitory effects of soybean oligosaccharides and water-soluble soybean fibre on formation of putrefactive compounds from soy protein by gut microbiota[J].International Journal of Biological Macromolecules,2017,97:173-180.
[15]KORPELA K,SALONEN A,VIRTA L J,et al.Intestinal microbiome is related to lifetime antibiotic use in Finnish preschool children[J].Nature Communications,2016,7:10410.
[16]KORPELA K,DE VOS W M.Antibiotic use in childhood alters the gut microbiota and predisposes to overweight[J].Microbial Cell,2016,3(7):296-298.
[17]VRIEZE A,OUT C,FUENTES S,et al.Impact of oral vancomycin on gut microbiota,bile acid metabolism,and insulin sensitivity[J].Journal of Hepatology,2014,60:824-831.
[18]CANDON S,PEREZ-ARROYO A,MARQUET C,et al.Antibiotics in early life alter the gut microbiome and increase disease incidence in a spontaneous mouse model of autoimmune insulin-dependent diabetes[J].PLoS One,2015,10(5):125448.
[19]CHO I,YAMANISHI S,COX L,et al.Antibiotics in early life alter the murine colonic microbiome and adiposity[J].Nature,2012,488:621-626.
[20]LOZUPONE C A,STOMBAUGH J H,GORDON J I,et al.Diversity,stability and resilience of the human gut microbiota[J].Nature,2012,489(7415):220-230.
[21]KOIDO S,OHKUSA T,KAJIURA T,et al.Long-term alteration of intestinal microbiota in patients with ulcerative colitis by antibiotic combination therapy[J].PLoS One,2014,9(1):86702.
[22]REESE A T,CHO E H,KLITZMAN B,et al.Antibiotic-induced changes in the microbiota disrupt redox dynamics inthe gut[J].Elife,2018,7:35987.
[23]JIANG X Y,ZHAO X,ZOU L Y,et al.Moderate exercise induces shift in the composition of human gut microbiota[J].Journal of Third Military Medical University,2017,39(18):1824-1831.
[24]ALLEN J M,MAILING L J,COHRS J,et al.Exercise training-induced modification of the gut microbiota persists after microbiota colonization and attenuates the response to chemically-induced colitis in gnotobiotic mice[J].Gut Microbes,2017,1:1-16.
[25]JACOB M A,LUCY J M,GRACE M N,et al.Exercise alters gut microbiota composition and function in lean and obese humans[J].Medicine&Science in Sports&Exercise,2017,50(4):747-757.
[26]CHOI J J,EUM S Y,RAMPERSAUD E,et al.Exercise attenuates PCB-induced changes in the mouse gut microbiome[J].Environmental Health Perspectives,2013,121(6):725-730.
[27]GOODRICH J K,WATERS J L,POOLE A C,et al.Human genetics shape the gut microbiome[J].Cell,2014,159(4):789-799.
[28]ROTHSCHILD D,WEISSBROD O,BARKAN E,et al.Environment dominates over host genetics in shaping human gut microbiota[J].Nature,2018,555(7695):210-215.
[29]STANISLAWSKI M A,DABELEA D,WAGNER B D,et al.Pre-pregnancy weight,gestational weight gain,and the gut microbiota of mothers and their infants[J].Microbiome,2017,5(1):113.
[30]POUTAHIDIS T,VARIAN B J,LEVKOVICH T,et al.Dietary microbes modulate transgenerational cancer risk[J].Cancer Research,2015,75(7):1197-1204.
[31]GENSOLLEN T,IYER S S,KASPER D L,et al.How colonization by microbiota in early life shapes the immune system[J].Science,2016,352(6285):539-544.
[32]SCHULFER A F,BATTAGLIA T,ALVAREZ Y,et al.Intergenerational transfer of antibiotic-perturbed microbiota enhances colitis in susceptible mice[J].Nature Microbiology,2018,3(2):234-242.
[33]LARSEN P E,DAI Y.Metabolome of human gut microbiome is predictive of host dysbiosis[J].Gigascience,2015,4:42.
[34]GOMEZ DE AGERO M,GANAL-VONARBURG S C,FUHRER T,et al.The maternal microbiota drives early postnatal innate immune development[J].Science,2016,351(6279):1296-1302.
[35]LOEWEN K I,MONCHKA B,MAHMUD S M,et al.Prenatal antibiotic exposure and childhood asthma:A populationbased study[J].Uropean Respiratory Journal,2018,52(1):1702070.
[36]ARRIETA M C,STIEMSMA L T,DIMITRIU P A,et al.Early infancy microbial and metabolic alterations affect risk of childhood asthma[J].Science Translational Medicine,2015,7(307):307ra152.
[37]OLSZAK T,AN D,ZEISSIG S,et al.Blumberg,microbial exposure during early life has persistent effects on natural killer T cell function[J].Science,2012,336:489-493.
[38]COX L M,YAMANISHI S,SOHN J,et al.Altering the intestinal microbiota during a critical developmental window has lasting metabolic consequences[J].Cell,2014,158:705-721.
[39]KNOOP K A,GUSTAFSSON J K,MCDONALD K G,et al.Microbial antigen encounter during apreweaning interval is critical for tolerance to gut bacteria[J].Science Immunology,2017,2(18):1314.
[40]YATSUNENKO T,REY F E,MANARY M J,et al.Human gut microbiome viewed across age and geography[J].Nature,2012,486:222-227.
[41]RUSSLER-GERMAIN E V,RENGARAJAN S,HSIEH C S.Antigen-specific regulatory T cell responses to intestinal microbiota[J].Mucosal Immunology,2017,10(6):1375-1386.
[42]LEE J,YANG W,HOSTETLER A,et al.Characterization of the anti-inflammatory Lactobacillus reuteri BM36301and its probiotic benefits on aged mice[J].BMC Microbiology,2016,16:69.
[43]DESHMUKH H S,LIU Y,MENKITI O R,et al.The microbiota regulates neutrophil homeostasis and host resistance to Escherichia coli K1sepsis in neonatal mice[J].Nature Medicine,2014(20):524-530.
[44]FURUSAWA Y,OBATA Y,FUKUDA S,et al.Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells[J].Nature,2013,504:446-450.
[45]KIM Y G,SAKAMOTO K,SEO S U,et al.Neonatal acquisition of Clostridia species protects against colonization by bacterial pathogens[J].Science,2017,356:315-319.
[46]ASHLEY L S,GEORGE P C,GERARD E K,et al.The microbial metabolite desaminotyrosine protects from influenzathrough type I interferon[J].Science,2017,357(6350):498-502.
[47]SINGH A,SARANGI A N,GOEL A,et al.Effect of administration of a probiotic preparation on gut microbiota and immune response in healthy women in India:An open-label,single-arm pilot study[J].BMC Gastroenterol,2018,18(1):85.
[48]CHU H,KHOSRAVI A,KUSUMAWARDHANI I P,et al.Gene-microbiota interactions contribute to the pathogenesis of inflammatory bowel disease[J].Science,2016,352:1116-1120.
[49]PAUL B,BARNES S,DEMARK-WAHNEFRIED W,et al.Influences of diet and the gut microbiome on epigenetic modulation in cancer and other diseases[J].Clinical Epigenetics,2015,7:112.
[50]GEURTS L,EVERARD A,VAN HUL M,et al.Adipose tissue NAPE-PLD controls fat mass development by altering the browning process and gut microbiota[J].Nature Communications,2015,6:6495.
[51]BLAUT M I.Gut microbiota and energy balance:Role in obesity[J].Proceedings of The Nutrition Society,2015,74(3):227-234.
[52]ELLEKILDE M,KRYCH L,HANSEN C H,et al.Characterization of the gut microbiota in leptin deficient obese miceCorrelation to inflammatory and diabetic parameters[J].Research in Veterinary Science,2014,96(2):241-250.
[53]SUAREZ-ZAMORANO N,FABBIANO S,CHEVALIER C,et al.Microbiota depletion promotes browning of white adipose tissue and reduces obesity[J].Nature Medicine,2015,21:1497-1501.
[54]LI G,XIE C,LU S,et al.Intermittent fasting promotes white adipose browning and decreases obesity by shaping the gut microbiota[J].Cell Metab,2017,26(5):801.
[55]ZHANG C,ZHAO L.Strain-level dissection of the contribution of the gut microbiome to human metabolic disease[J].Genome Medicine,2016,8(1):41.
[56]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,2016,65:426-436.
[57]KUMAR H,LUND R,LAIHO A,et al.Gut microbiota as an epigenetic regulator:Pilot study based on whole-genome methylation analysis[J].MBio,2014,5(6):2113-2114.
[58]FEI N,ZHAO L.An opportunistic pathogen isolated from the gut of an obese human causes obesity in germfree mice[J].ISME Journal,2013,7:880-884.
[59]HULLAR M A J,FU B C.Diet,the gut microbiome,and epigenetics[J].Cancer Journal,2014,20(3):170-175.
[60]SEARS C L,GARRETT W S.Microbes,microbiota,and colon cancer[J].Cell Host Microbe,2014,15:317-328.
[61]GAGNIRE J,RAISCH J,VEZIANT J,et al.Gut microbiota imbalance and colorectal cancer[J].World Journal of Gastroenterology,2016,22(2):501-518.
[62]RUBINSTEIN M R,WANG X,LIU W,et al.Fusobacterium nucleatum promotes colorectal carcinogenesis by modulating E-cadherin/β-catenin signaling via its FadA adhesion[J].Cell Host Microbe,2013,14(2):195-206.
[63]ARTHUR J C,PEREZ-CHANONA E,MHLBAUER M,et al.Intestinal inflammation targets cancer-inducing activity of the microbiota[J].Science,2012,338(6103):120-123.
[64]BAXTER N T,ZACKULAR J P,CHEN G Y,et al.Structure of the gut microbiome following colonization with human feces determines colonic tumor burden[J].Microbiome,2014,2:20.
[65]NG K M,FERREYRA J A,HIGGINBOTTOM S K,et al.Microbiota-liberated host sugars facilitate post-antibiotic expansion of enteric pathogens[J].Nature,2013,502(7469):96-99.
[66]VETIZOU M,PITT J M,DAILLERE R,et al.Anticancer immunotherapy by CTLA-4blockade relies on the gut microbiota[J].Science,2015,350(6264):1079-1084.
[67]IIDA N,DZUTSEV A,STEWART C A,et al.Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment[J].Science,2013,342(6161):967-970.
[68]GUTHRIE L,GUPTA S,DAILY J,et al.Human microbiome signatures of differential colorectal cancer drug metabolism[J].Biofilms and Microbiomes,2017,3:27.
[69]CLARK R I,SALAZAR A,YAMADA R,et al.Distinct shifts in microbiota composition during drosophila aging impair intestinal function and drive mortality[J].Cell Reports,2015,12(10):1656-1667.
[70]WESTFALL S,LOMIS N,PRAKASH S.Longevity extension in Drosophilathrough gut-brain communication[J].Scientific Reports,2018,8(1):8362.
[71]THEVARANJAN N,PUCHTA A,SCHULZ C,et al.Age-associated microbial dysbiosis promotes intestinal permea-bility,systemic inflammation,and macrophage dysfunction[J].Cell Host Microbe,2017,21(4):455-466.
[72]CALLAWAY E.'Young poo'makes aged fish live longer[J].Nature,2017,544(7649):147.
[73]PORTAL-CELHAY C,BRADLEY E R,BLASER M J.Control of intestinal bacterial proliferation in regulation of lifespan in Caenorhabditis elegans[J].BMC Microbiol,2012,12:49.
[74]NGUYEN T P,CLARKE C F.Folate status of gut microbiome affects Caenorhabditis elegans lifespan[J].BMC Biol,2012,10:66.
[75]VIRK B,CORREIA G,DIXON D P,et al.Excessive folate synthesis limits lifespan in the C.elegans:E.coli aging model[J].BMC Biology,2012,10:67.
[76]HNNINEN A,TOIVONEN R,PYSTI S,et al.Akkermansia muciniphila induces gut microbiota remodelling and controls islet autoimmunity in NOD mice[J].Gut,2018,67(8):1445-1453.
[77]CUI B,LI P,XU L,et al.Step-up fecal microbiota transplantation strategy:A pilot study for steroid-dependent ulcerative colitis[J].Journal of Translational Medicine,2015,13:298.
[78]MUHAMMAD U S,MUHAMMAD Z S,JRG M S,et al.Molecular analysis of the gut microbiome of diabetic rats supplemented with prebiotic,probiotic,and synbiotic foods[J].International Journal of Diabetes in Developing Countries,2017,37(4):419-425.
[79]PARK D Y,AHN Y T,HUH C S,et al.Dual probiotic strains suppress high fructose-induced metabolic syndrome[J].World Journal of Gastroenterology,2013,19:274-283.
[80]YOUN H N,LEE D H,LEE Y N,et al.Intranasal administration of live lactobacillus species facilitates protection against influenza virus infection in mice[J].Antiviral Research,2012,93:138-143.
[81]JUNG Y J,LEE Y T,NGO V L,et al.Heat-killed lactobacillus casei confers broad protection against infuenza A virus primary infection and develops heterosubtypic immunity against future secondary infection[J].Scientific Reports,2017,7(1):17360.
[82]ZHAO L P,ZHANG F,DING X Y,et al.Gut bacteria selectively promoted by dietary fibers alleviate type 2diabetes[J].Science,2018,359:1151-1156.
[83]SALAZAR N,DEWULF E M,NEYRINCK A M,et al.Inulin-type fructans modulate intestinal Bifidobacterium species populations and decrease fecal short-chain fatty acids in obese women[J].Clinical Nutrition,2015,34(3):501-507.
[84]LI Q,YAN Q,CHEN J,et al.Molecular characterization of an ice nucleation protein variant(InaQ)fromPseudomonas syringae and the analysis of its transmembrane transport activity in Escherichia coli[J].International Journal of Biological Sciences,2012,8(8):1097-1108.
[85]CHUN L H,HUI Q T,KOON J C,et al.Engineered commensal microbes for diet-mediated colorectal-cancer chemoprevention[J].Nature Biomedical Engineering,2018,2:27-37.
[86]FRAHM M,FELGNER S,KOCIJANCIC D,et al.Efficiency of conditionally attenuated salmonella enterica serovar typhimurium in acterium-mediated tumor therapy[J].MBio,2015,6(2).pii:e00254-15.
[87]FELFOUL O,MOHAMMADI M,TAHERKHANI S,et al.Magneto-aerotactic bacteria deliver drug-containing nanoliposomes to tumour hypoxic regions[J].Nat Nanotechnol,2016,11(11):941-947.
[88]MATSON V,FESSLER J,BAO R,et al.The commensal microbiome is associated with anti-PD-1efficacy in metastaticmelanoma patients[J].Science,2018,359:104-108.
[89]KAISER J.Gut microbes shape response to cancer immunotherapy[J].Science,2017,358(6363):573.
[90]SIVAN A,CORRALES L,HUBERT N,et al.Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1efficacy[J].Science,2015,350(6264):1084-1089.
[91]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.
[92]GOPALAKRISHNAN V,SPENCER C N,NEZI L,et al.Gut microbiome modulates response to anti-PD-1immunotherapy in melanoma patients[J].Science,2018,359(6371):97-103.
[93]VETIZOU M,PITT J M,DAILLERE R,et al.Anticancer immunotherapy by CTLA-4blockade relies on the gut microbiota[J].Science,2015,350(6264):1079.
[94]VIAUD S,SACCHERI F,MIGNOT G,et al.The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide[J].Science,2013,342(6161):971-976.
[95]KIM J K,CHOI M S,JEONG J J,et al.Effect of probiotics on pharmacokinetics of orally administered acetaminophenin mice[J].Drug Metabolism and Disposition,2018,46(2):122-130.
[96]JACKSON M A,VERDI S,MAXAN M E,et al.Gut microbiota associations with common diseases and prescription medications in a population-based cohort[J].Nature Communications,2018,9(1):2655.
[97]HOYLES L,FERNNDEZ-REAL J M,FEDERICI M,et al.Molecular phenomics and metagenomics of hepatic steatosis in non-diabetic obese women[J].Nature Medicine,2018,24(7):1070-1080.
[98]KOREM T,ZEEVI D,SUEZ J,et al.Growth dynamics of gut microbiota in health and disease inferred from single metagenomic samples[J].Science,2015,349(6252):1101-1106.
[2]GROER M W,LUCIANO A A,DISHAW L J,et al.Development of the preterm infant gut microbiome:A research priority[J].Microbiome,2014,2:38.
[3]FRESE S A,PARKER K,CALVERT C C,et al.Diet shapes the gut microbiome of pigs during nursing and weaning[J].Microbiome,2015,3:28.
[4]KOVATCHEVA-DATCHARY P,NILSSON A,AKRAMI R,et al.Dietary fiber-induced improvement in glucose metabolism is associated with increased abundance of Prevotella[J].Cell Metabolism,2015,22:971-982.
[5]EID N,ENANI S,WALTON G,et al.The impact of date palm fruits and their component polyphenols,on gut microbial ecology,bacterial metabolites and colon cancer cell proliferation[J].International Journal of Food Sciences and Nutrition,2014,3:e46.
[6]BAI G,TSURUTA T,NISHINO N.Dietary soy,meat,and fish proteins modulate the effects of prebiotic raffinose on composition an fermentation of gut microbiota in rats[J].International Journal of Food Sciences and Nutrition,2018,69(4):480-487.
[7]DAVID L A,MAURICE C F,CARMODY R N,et al.Diet rapidly and reproducibly alters the human gut microbiome[J].Nature,2014,505:559-563.
[8]CAESAR R,TREMAROLI V,KOVATCHEVA-DATCHARY P,et al.Crosstalk between gut microbiota and dietary lipids aggravates WAT inflammation through TLR signaling[J].Cell Metabolism,2015,22:658-668.
[9]CUERVO A,HEVIA A,LPEZ P,et al.Phenolic compounds from red wine and coffee are associated with specific intestinal microorganisms in allergic subjects[J].Food Function,2015,7(1):104-109.
[10]COTILLARD A,KENNEDY S P,KONG L C,et al.Dietary intervention impact on gut microbial gene richness[J].Nature,2013,500:585-588.
[11]ETXEBERRIA U,FERNNDEZQUINTELA A,MILAGRO F I,et al.Impact of polyphenols and polyphenol-rich dietary sources on gut microbiota composition[J].Journal of Agricultural&Food Chemistry,2013,61(40):9517-9533.
[12]WILCK N,MATUS M G,KEARNEY S M,et al.Salt-responsive gut commensal modulates TH17axis and disease[J].Nature,2017,551(7682):585-589.
[13]DE A M,MONTEMURNO E,VANNINI L,et al.Effect of whole-grain barley on the human fecal microbiota and metabolome[J].Applied&Environmental Microbiology,2015,81(22):7945-7956.
[14]NAKATA T,KYOUI D,TAKAHASHI H,et al.Inhibitory effects of soybean oligosaccharides and water-soluble soybean fibre on formation of putrefactive compounds from soy protein by gut microbiota[J].International Journal of Biological Macromolecules,2017,97:173-180.
[15]KORPELA K,SALONEN A,VIRTA L J,et al.Intestinal microbiome is related to lifetime antibiotic use in Finnish preschool children[J].Nature Communications,2016,7:10410.
[16]KORPELA K,DE VOS W M.Antibiotic use in childhood alters the gut microbiota and predisposes to overweight[J].Microbial Cell,2016,3(7):296-298.
[17]VRIEZE A,OUT C,FUENTES S,et al.Impact of oral vancomycin on gut microbiota,bile acid metabolism,and insulin sensitivity[J].Journal of Hepatology,2014,60:824-831.
[18]CANDON S,PEREZ-ARROYO A,MARQUET C,et al.Antibiotics in early life alter the gut microbiome and increase disease incidence in a spontaneous mouse model of autoimmune insulin-dependent diabetes[J].PLoS One,2015,10(5):125448.
[19]CHO I,YAMANISHI S,COX L,et al.Antibiotics in early life alter the murine colonic microbiome and adiposity[J].Nature,2012,488:621-626.
[20]LOZUPONE C A,STOMBAUGH J H,GORDON J I,et al.Diversity,stability and resilience of the human gut microbiota[J].Nature,2012,489(7415):220-230.
[21]KOIDO S,OHKUSA T,KAJIURA T,et al.Long-term alteration of intestinal microbiota in patients with ulcerative colitis by antibiotic combination therapy[J].PLoS One,2014,9(1):86702.
[22]REESE A T,CHO E H,KLITZMAN B,et al.Antibiotic-induced changes in the microbiota disrupt redox dynamics inthe gut[J].Elife,2018,7:35987.
[23]JIANG X Y,ZHAO X,ZOU L Y,et al.Moderate exercise induces shift in the composition of human gut microbiota[J].Journal of Third Military Medical University,2017,39(18):1824-1831.
[24]ALLEN J M,MAILING L J,COHRS J,et al.Exercise training-induced modification of the gut microbiota persists after microbiota colonization and attenuates the response to chemically-induced colitis in gnotobiotic mice[J].Gut Microbes,2017,1:1-16.
[25]JACOB M A,LUCY J M,GRACE M N,et al.Exercise alters gut microbiota composition and function in lean and obese humans[J].Medicine&Science in Sports&Exercise,2017,50(4):747-757.
[26]CHOI J J,EUM S Y,RAMPERSAUD E,et al.Exercise attenuates PCB-induced changes in the mouse gut microbiome[J].Environmental Health Perspectives,2013,121(6):725-730.
[27]GOODRICH J K,WATERS J L,POOLE A C,et al.Human genetics shape the gut microbiome[J].Cell,2014,159(4):789-799.
[28]ROTHSCHILD D,WEISSBROD O,BARKAN E,et al.Environment dominates over host genetics in shaping human gut microbiota[J].Nature,2018,555(7695):210-215.
[29]STANISLAWSKI M A,DABELEA D,WAGNER B D,et al.Pre-pregnancy weight,gestational weight gain,and the gut microbiota of mothers and their infants[J].Microbiome,2017,5(1):113.
[30]POUTAHIDIS T,VARIAN B J,LEVKOVICH T,et al.Dietary microbes modulate transgenerational cancer risk[J].Cancer Research,2015,75(7):1197-1204.
[31]GENSOLLEN T,IYER S S,KASPER D L,et al.How colonization by microbiota in early life shapes the immune system[J].Science,2016,352(6285):539-544.
[32]SCHULFER A F,BATTAGLIA T,ALVAREZ Y,et al.Intergenerational transfer of antibiotic-perturbed microbiota enhances colitis in susceptible mice[J].Nature Microbiology,2018,3(2):234-242.
[33]LARSEN P E,DAI Y.Metabolome of human gut microbiome is predictive of host dysbiosis[J].Gigascience,2015,4:42.
[34]GOMEZ DE AGERO M,GANAL-VONARBURG S C,FUHRER T,et al.The maternal microbiota drives early postnatal innate immune development[J].Science,2016,351(6279):1296-1302.
[35]LOEWEN K I,MONCHKA B,MAHMUD S M,et al.Prenatal antibiotic exposure and childhood asthma:A populationbased study[J].Uropean Respiratory Journal,2018,52(1):1702070.
[36]ARRIETA M C,STIEMSMA L T,DIMITRIU P A,et al.Early infancy microbial and metabolic alterations affect risk of childhood asthma[J].Science Translational Medicine,2015,7(307):307ra152.
[37]OLSZAK T,AN D,ZEISSIG S,et al.Blumberg,microbial exposure during early life has persistent effects on natural killer T cell function[J].Science,2012,336:489-493.
[38]COX L M,YAMANISHI S,SOHN J,et al.Altering the intestinal microbiota during a critical developmental window has lasting metabolic consequences[J].Cell,2014,158:705-721.
[39]KNOOP K A,GUSTAFSSON J K,MCDONALD K G,et al.Microbial antigen encounter during apreweaning interval is critical for tolerance to gut bacteria[J].Science Immunology,2017,2(18):1314.
[40]YATSUNENKO T,REY F E,MANARY M J,et al.Human gut microbiome viewed across age and geography[J].Nature,2012,486:222-227.
[41]RUSSLER-GERMAIN E V,RENGARAJAN S,HSIEH C S.Antigen-specific regulatory T cell responses to intestinal microbiota[J].Mucosal Immunology,2017,10(6):1375-1386.
[42]LEE J,YANG W,HOSTETLER A,et al.Characterization of the anti-inflammatory Lactobacillus reuteri BM36301and its probiotic benefits on aged mice[J].BMC Microbiology,2016,16:69.
[43]DESHMUKH H S,LIU Y,MENKITI O R,et al.The microbiota regulates neutrophil homeostasis and host resistance to Escherichia coli K1sepsis in neonatal mice[J].Nature Medicine,2014(20):524-530.
[44]FURUSAWA Y,OBATA Y,FUKUDA S,et al.Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells[J].Nature,2013,504:446-450.
[45]KIM Y G,SAKAMOTO K,SEO S U,et al.Neonatal acquisition of Clostridia species protects against colonization by bacterial pathogens[J].Science,2017,356:315-319.
[46]ASHLEY L S,GEORGE P C,GERARD E K,et al.The microbial metabolite desaminotyrosine protects from influenzathrough type I interferon[J].Science,2017,357(6350):498-502.
[47]SINGH A,SARANGI A N,GOEL A,et al.Effect of administration of a probiotic preparation on gut microbiota and immune response in healthy women in India:An open-label,single-arm pilot study[J].BMC Gastroenterol,2018,18(1):85.
[48]CHU H,KHOSRAVI A,KUSUMAWARDHANI I P,et al.Gene-microbiota interactions contribute to the pathogenesis of inflammatory bowel disease[J].Science,2016,352:1116-1120.
[49]PAUL B,BARNES S,DEMARK-WAHNEFRIED W,et al.Influences of diet and the gut microbiome on epigenetic modulation in cancer and other diseases[J].Clinical Epigenetics,2015,7:112.
[50]GEURTS L,EVERARD A,VAN HUL M,et al.Adipose tissue NAPE-PLD controls fat mass development by altering the browning process and gut microbiota[J].Nature Communications,2015,6:6495.
[51]BLAUT M I.Gut microbiota and energy balance:Role in obesity[J].Proceedings of The Nutrition Society,2015,74(3):227-234.
[52]ELLEKILDE M,KRYCH L,HANSEN C H,et al.Characterization of the gut microbiota in leptin deficient obese miceCorrelation to inflammatory and diabetic parameters[J].Research in Veterinary Science,2014,96(2):241-250.
[53]SUAREZ-ZAMORANO N,FABBIANO S,CHEVALIER C,et al.Microbiota depletion promotes browning of white adipose tissue and reduces obesity[J].Nature Medicine,2015,21:1497-1501.
[54]LI G,XIE C,LU S,et al.Intermittent fasting promotes white adipose browning and decreases obesity by shaping the gut microbiota[J].Cell Metab,2017,26(5):801.
[55]ZHANG C,ZHAO L.Strain-level dissection of the contribution of the gut microbiome to human metabolic disease[J].Genome Medicine,2016,8(1):41.
[56]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,2016,65:426-436.
[57]KUMAR H,LUND R,LAIHO A,et al.Gut microbiota as an epigenetic regulator:Pilot study based on whole-genome methylation analysis[J].MBio,2014,5(6):2113-2114.
[58]FEI N,ZHAO L.An opportunistic pathogen isolated from the gut of an obese human causes obesity in germfree mice[J].ISME Journal,2013,7:880-884.
[59]HULLAR M A J,FU B C.Diet,the gut microbiome,and epigenetics[J].Cancer Journal,2014,20(3):170-175.
[60]SEARS C L,GARRETT W S.Microbes,microbiota,and colon cancer[J].Cell Host Microbe,2014,15:317-328.
[61]GAGNIRE J,RAISCH J,VEZIANT J,et al.Gut microbiota imbalance and colorectal cancer[J].World Journal of Gastroenterology,2016,22(2):501-518.
[62]RUBINSTEIN M R,WANG X,LIU W,et al.Fusobacterium nucleatum promotes colorectal carcinogenesis by modulating E-cadherin/β-catenin signaling via its FadA adhesion[J].Cell Host Microbe,2013,14(2):195-206.
[63]ARTHUR J C,PEREZ-CHANONA E,MHLBAUER M,et al.Intestinal inflammation targets cancer-inducing activity of the microbiota[J].Science,2012,338(6103):120-123.
[64]BAXTER N T,ZACKULAR J P,CHEN G Y,et al.Structure of the gut microbiome following colonization with human feces determines colonic tumor burden[J].Microbiome,2014,2:20.
[65]NG K M,FERREYRA J A,HIGGINBOTTOM S K,et al.Microbiota-liberated host sugars facilitate post-antibiotic expansion of enteric pathogens[J].Nature,2013,502(7469):96-99.
[66]VETIZOU M,PITT J M,DAILLERE R,et al.Anticancer immunotherapy by CTLA-4blockade relies on the gut microbiota[J].Science,2015,350(6264):1079-1084.
[67]IIDA N,DZUTSEV A,STEWART C A,et al.Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment[J].Science,2013,342(6161):967-970.
[68]GUTHRIE L,GUPTA S,DAILY J,et al.Human microbiome signatures of differential colorectal cancer drug metabolism[J].Biofilms and Microbiomes,2017,3:27.
[69]CLARK R I,SALAZAR A,YAMADA R,et al.Distinct shifts in microbiota composition during drosophila aging impair intestinal function and drive mortality[J].Cell Reports,2015,12(10):1656-1667.
[70]WESTFALL S,LOMIS N,PRAKASH S.Longevity extension in Drosophilathrough gut-brain communication[J].Scientific Reports,2018,8(1):8362.
[71]THEVARANJAN N,PUCHTA A,SCHULZ C,et al.Age-associated microbial dysbiosis promotes intestinal permea-bility,systemic inflammation,and macrophage dysfunction[J].Cell Host Microbe,2017,21(4):455-466.
[72]CALLAWAY E.'Young poo'makes aged fish live longer[J].Nature,2017,544(7649):147.
[73]PORTAL-CELHAY C,BRADLEY E R,BLASER M J.Control of intestinal bacterial proliferation in regulation of lifespan in Caenorhabditis elegans[J].BMC Microbiol,2012,12:49.
[74]NGUYEN T P,CLARKE C F.Folate status of gut microbiome affects Caenorhabditis elegans lifespan[J].BMC Biol,2012,10:66.
[75]VIRK B,CORREIA G,DIXON D P,et al.Excessive folate synthesis limits lifespan in the C.elegans:E.coli aging model[J].BMC Biology,2012,10:67.
[76]HNNINEN A,TOIVONEN R,PYSTI S,et al.Akkermansia muciniphila induces gut microbiota remodelling and controls islet autoimmunity in NOD mice[J].Gut,2018,67(8):1445-1453.
[77]CUI B,LI P,XU L,et al.Step-up fecal microbiota transplantation strategy:A pilot study for steroid-dependent ulcerative colitis[J].Journal of Translational Medicine,2015,13:298.
[78]MUHAMMAD U S,MUHAMMAD Z S,JRG M S,et al.Molecular analysis of the gut microbiome of diabetic rats supplemented with prebiotic,probiotic,and synbiotic foods[J].International Journal of Diabetes in Developing Countries,2017,37(4):419-425.
[79]PARK D Y,AHN Y T,HUH C S,et al.Dual probiotic strains suppress high fructose-induced metabolic syndrome[J].World Journal of Gastroenterology,2013,19:274-283.
[80]YOUN H N,LEE D H,LEE Y N,et al.Intranasal administration of live lactobacillus species facilitates protection against influenza virus infection in mice[J].Antiviral Research,2012,93:138-143.
[81]JUNG Y J,LEE Y T,NGO V L,et al.Heat-killed lactobacillus casei confers broad protection against infuenza A virus primary infection and develops heterosubtypic immunity against future secondary infection[J].Scientific Reports,2017,7(1):17360.
[82]ZHAO L P,ZHANG F,DING X Y,et al.Gut bacteria selectively promoted by dietary fibers alleviate type 2diabetes[J].Science,2018,359:1151-1156.
[83]SALAZAR N,DEWULF E M,NEYRINCK A M,et al.Inulin-type fructans modulate intestinal Bifidobacterium species populations and decrease fecal short-chain fatty acids in obese women[J].Clinical Nutrition,2015,34(3):501-507.
[84]LI Q,YAN Q,CHEN J,et al.Molecular characterization of an ice nucleation protein variant(InaQ)fromPseudomonas syringae and the analysis of its transmembrane transport activity in Escherichia coli[J].International Journal of Biological Sciences,2012,8(8):1097-1108.
[85]CHUN L H,HUI Q T,KOON J C,et al.Engineered commensal microbes for diet-mediated colorectal-cancer chemoprevention[J].Nature Biomedical Engineering,2018,2:27-37.
[86]FRAHM M,FELGNER S,KOCIJANCIC D,et al.Efficiency of conditionally attenuated salmonella enterica serovar typhimurium in acterium-mediated tumor therapy[J].MBio,2015,6(2).pii:e00254-15.
[87]FELFOUL O,MOHAMMADI M,TAHERKHANI S,et al.Magneto-aerotactic bacteria deliver drug-containing nanoliposomes to tumour hypoxic regions[J].Nat Nanotechnol,2016,11(11):941-947.
[88]MATSON V,FESSLER J,BAO R,et al.The commensal microbiome is associated with anti-PD-1efficacy in metastaticmelanoma patients[J].Science,2018,359:104-108.
[89]KAISER J.Gut microbes shape response to cancer immunotherapy[J].Science,2017,358(6363):573.
[90]SIVAN A,CORRALES L,HUBERT N,et al.Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1efficacy[J].Science,2015,350(6264):1084-1089.
[91]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.
[92]GOPALAKRISHNAN V,SPENCER C N,NEZI L,et al.Gut microbiome modulates response to anti-PD-1immunotherapy in melanoma patients[J].Science,2018,359(6371):97-103.
[93]VETIZOU M,PITT J M,DAILLERE R,et al.Anticancer immunotherapy by CTLA-4blockade relies on the gut microbiota[J].Science,2015,350(6264):1079.
[94]VIAUD S,SACCHERI F,MIGNOT G,et al.The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide[J].Science,2013,342(6161):971-976.
[95]KIM J K,CHOI M S,JEONG J J,et al.Effect of probiotics on pharmacokinetics of orally administered acetaminophenin mice[J].Drug Metabolism and Disposition,2018,46(2):122-130.
[96]JACKSON M A,VERDI S,MAXAN M E,et al.Gut microbiota associations with common diseases and prescription medications in a population-based cohort[J].Nature Communications,2018,9(1):2655.
[97]HOYLES L,FERNNDEZ-REAL J M,FEDERICI M,et al.Molecular phenomics and metagenomics of hepatic steatosis in non-diabetic obese women[J].Nature Medicine,2018,24(7):1070-1080.
[98]KOREM T,ZEEVI D,SUEZ J,et al.Growth dynamics of gut microbiota in health and disease inferred from single metagenomic samples[J].Science,2015,349(6252):1101-1106.