色氨酸微生物代谢产物的肠道免疫调节作用及其机制
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摘要
肠道微生物参与营养吸收、物质代谢、肠道免疫调节等重要的生理过程,并与多种疾病的发生有关系。作为一种必需氨基酸,色氨酸及其微生物代谢产物包括吲哚和吲哚酸衍生物等在维持肠道稳态方面发挥着重要的作用。芳香烃受体(AhR)通过结合其配体(色氨酸微生物代谢产物)调节肠道免疫,有助于维持肠道免疫平衡。本综述主要阐述色氨酸微生物代谢产物发挥维持肠道免疫平衡、维护肠道健康作用的机制,以期为外源色氨酸预防或治疗肠道炎症反应提供新思路。
The intestinal microbiota plays a crucial role in nutrition up-take,component metabolism,as well as intestinal immune modulation.As an essential amino acid,tryptophan and its microbiota metabolites,such as indole and indolic acid derivatives play an important role in the balance between intestinal immune tolerance and intestinal microbiota maintenance.The aryl hydrocarbon receptor(AhR) mediates the modulation of intestinal immune by tryptophan microbiota metabolites(as ligands of AhR),which is beneficial for immune homeostasis.This article mainly clarified the mechanism of intestinal microbiota metabolites regulating the intestinal immune balance and maintaining intestinal health,which provided a new insight on how tryptophan as a nutritional supplementation to prevent or alleviate intestinal inflammation.
The intestinal microbiota plays a crucial role in nutrition up-take,component metabolism,as well as intestinal immune modulation.As an essential amino acid,tryptophan and its microbiota metabolites,such as indole and indolic acid derivatives play an important role in the balance between intestinal immune tolerance and intestinal microbiota maintenance.The aryl hydrocarbon receptor(AhR) mediates the modulation of intestinal immune by tryptophan microbiota metabolites(as ligands of AhR),which is beneficial for immune homeostasis.This article mainly clarified the mechanism of intestinal microbiota metabolites regulating the intestinal immune balance and maintaining intestinal health,which provided a new insight on how tryptophan as a nutritional supplementation to prevent or alleviate intestinal inflammation.
引文
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[3]GANAL S C,SANOS S L,KALLFASS C,et al.Priming of natural killer cells by nonmucosal mononuclear phagocytes requires instructive signals from commensal microbiota[J].Immunity,2012,37(1):171-186.
[4]VATANEN T,KOSTIC A D,D'HENNEZEL E,et al.Variation in microbiome LPS immunogenicity contributes to autoimmunity in humans[J].Cell,2016,165(6):842-853.
[5]HASHIMOTO T,PERLOT T,REHMAN A,et al.ACE2 links amino acid malnutrition to microbial ecology and intestinal inflammation[J].Nature,2012,487(7408):477-481.
[6]KIM C J,KOVACS-NOLAN J A,YANG C B,et al.L-Tryptophan exhibits therapeutic function in a porcine model of dextran sodium sulfate(DSS)-induced colitis[J].The Journal of Nutritional Biochemistry,2010,21(6):468-475.
[7]ISLAM J,SATO S,WATANABE K,et al.Dietary tryptophan alleviates dextran sodium sulfate-induced colitis through aryl hydrocarbon receptor in mice[J].The Journal of Nutritional Biochemistry,2017,42:43-50.
[8]ZELANTE T,IANNITTI R G,CUNHA C,e t al.Tryptophan catabolites from microbiota engage aryl hydrocarbon receptor and balance mucosal reactivity via interleukin-22[J].Immunity,2013,39(2):372-385.
[9]ETIENNE-MESMIN L,CHASSAING B,GEWIRTZA T.Tryptophan:a gut microbiota-derived metabolites regulating inflammation[J].World Journal of Gastrointestinal Pharmacology and Therapeutics,2017,8(1):7-9.
[10]YOKOYAMA M T,CARLSON J R.Microbial metabolites of tryptophan in the intestinal tract with special reference to skatole[J].The American Journal of Clinical Nutrition,1979,32(1):173-178.
[11]KESZTHELYI D,TROOST F J,MASCLEE A A M.Understanding the role of tryptophan and serotonin metabolism in gastrointestinal function[J].Neurogastroenterology&Motility,2009,21(12):1239-1249.
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[15]SMITH E A,MACFARLANE G T.Formation of phenolic and indolic compounds by anaerobic bacteria in the human large intestine[J].Microbial Ecology,1997,33(3):180-188.
[16]VENKATESH M,MUKHERJEE S,WANG H W,et al.Symbiotic bacterial metabolites regulate gastrointestinal barrier function via the xenobiotic sensor PXR and tolllike receptor 4[J].Immunity,2014,41(2):296-310.
[17]LAMAS B,RICHARD M L,LEDUCQ V,et al.CARD9 impacts colitis by altering gut microbiota metabolism of tryptophan into aryl hydrocarbon receptor ligands[J].Nature Medicine,2016,22(6):598-605.
[18]DAVID L A,MAURICE C F,CARMODY R N,et al.Diet rapidly and reproducibly alters the human gut microbiome[J].Nature,2014,505(7484):559-563.
[19]ROTHHAMMER V,MASCANFRONI I D,BUNSEL,e t al.Type I interferons and microbial metabolites of tryptophan modulate astrocyte activity and central nervous system inflammation via the aryl hydrocarbon receptor[J].Nature Medicine,2016,22(6):586-597.
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