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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Systemic gut microbial modulation of bile acid metabolism in host tissue compartments
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Systemic gut microbial modulation of bile acid metabolism in host tissue compartments

机译：宿主组织区室中胆汁酸代谢的全身肠道微生物调节

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摘要

We elucidate the detailed effects of gut microbial depletion on the bile acid sub-metabolome of multiple body compartments (liver, kidney, heart, and blood plasma) in rats. We use a targeted ultra-performance liquid chromatography with time of flight mass-spec- trometry assay to characterize the differential primary and secondary bile acid profiles in each tissue and show a major increase in the proportion of taurine-conjugated bile acids in germ-free (GF) and antibiotic (streptomycin/pehicillin)-treated rats. Although conjugated bile acids dominate the hepatic profile (97.0 ± 1.5%) of conventional animals, unconjugated bile acids comprise the largest proportion of the total measured bile acid profile in kidney (60.0 ± 10.4%) and heart (53.0 + 18.5%) tissues. In contrast, in the GF animal, taurine-conjugated bile acids (especially taurocholic acid and tauro-p-muricholic acid) dominated the bile acid profiles (liver: 96.0 ± 14.5%; kidney: 96 ± 1%; heart: 93 ± 1%;plasma: 93.0 ± 2.3%), with unconjugated and glycine-conjugated species representing a small proportion of the profile. Higher free taurine levels were found in GF livers compared with the conventional liver (5.1-fold; P < 0.001). Bile acid diversity was also lower in GF and antibiotic-treated tissues compared with conventional animals. Because bile acids perform important signaling functions, it is clear that these chemical communication networks are strongly influenced by microbial activities or modulation, as evidenced by farnesoid X receptor-regulated pathway transcripts. The presence of specific microbial bile acid co-metabolite patterns in peripheral tissues (including heart and kidney) implies a broader signaling role for these compounds and emphasizes the extent of symbiotic microbial influences in mammalian homeostasis.
机译：我们阐明了肠道微生物耗竭对大鼠多个体腔（肝脏，肾脏，心脏和血浆）的胆汁酸亚代谢组的详细影响。我们使用靶向超高效液相色谱和飞行时间质谱分析法来表征每个组织中不同的一级和二级胆汁酸谱，并表明在无菌菌体中牛磺酸缀合的胆汁酸比例显着增加（GF）和抗生素（链霉素/ pehicillin）处理的大鼠。尽管共轭胆汁酸在常规动物的肝组织中占主导地位（97.0±1.5％），但在肾脏（60.0±10.4％）和心脏（53.0 + 18.5％）组织中，未共轭胆汁酸占总胆汁酸谱的最大比例。相比之下，在GF动物中，牛磺酸结合的胆汁酸（尤其是牛磺胆酸和牛磺-对-多元酚酸）在胆汁酸谱中占主导地位（肝脏：96.0±14.5％；肾脏：96±1％；心脏：93±1 ％；血浆：93.0±2.3％），未结合和甘氨酸结合的物质占谱的一小部分。与常规肝相比，GF肝中游离牛磺酸水平更高（5.1倍； P <0.001）。与常规动物相比，GF和经抗生素处理的组织中的胆汁酸多样性也较低。由于胆汁酸具有重要的信号传导功能，因此很明显，这些化学通讯网络受到微生物活动或调节的强烈影响，如法呢素X受体调节的通路转录物所证明的那样。外周组织（包括心脏和肾脏）中特定的微生物胆汁酸共代谢物模式的存在暗示着这些化合物具有更广泛的信号传导作用，并强调了共生微生物对哺乳动物体内稳态的影响程度。

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  • 作者

    Jonathan R. Swann; Elizabeth J. Want; Florian M. Geier; Konstantina Spagou; Ian D. Wilson; James E. Sidaway; Jeremy K. Nicholson; Elaine Holmes;

  • 作者单位

    Biomolecular Medicine, Department of Surgery and Cancer, Faculty of Medicine, Imperial College, London SW7 2AZ, United Kingdom,Department of Food and Nutritional Sciences, School of Chemistry, Food and Pharmacy, The University of Reading, Reading RG6 6AP, United Kingdom;

    Biomolecular Medicine, Department of Surgery and Cancer, Faculty of Medicine, Imperial College, London SW7 2AZ, United Kingdom;

    Biomolecular Medicine, Department of Surgery and Cancer, Faculty of Medicine, Imperial College, London SW7 2AZ, United Kingdom;

    Biomolecular Medicine, Department of Surgery and Cancer, Faculty of Medicine, Imperial College, London SW7 2AZ, United Kingdom;

    AstraZeneca, Department of Clinical Pharmacology, Drug Metabolism and Pharmacokinetics;

    AstraZeneca, Global Safety Assessment, Cheshire SK10 4TG, United Kingdom;

    Biomolecular Medicine, Department of Surgery and Cancer, Faculty of Medicine, Imperial College, London SW7 2AZ, United Kingdom;

    Biomolecular Medicine, Department of Surgery and Cancer, Faculty of Medicine, Imperial College, London SW7 2AZ, United Kingdom;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    farnesoid x receptor; gut microbiota; tgr5; ultra-performance liquid chromatography mass spectrometry; g protein-coupled bile acid receptor 1;

    机译：法呢类x受体;肠道菌群;tgr5;超高效液相色谱质谱;g蛋白偶联胆汁酸受体1;

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