Biogeography of microbial bile acid transformations along the murine gut
Biogeography of microbial bile acid transformations along the murine gut
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DOI：
10.1194/jlr.ra120001021
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发表时间：
2020-11-01
影响因子：
6.5
通讯作者：
Bernier-Latmani, Rizlan
中科院分区：
文献类型：
--
作者：
Marion, Solenne;Desharnais, Lyne;Bernier-Latmani, Rizlan
胆汁酸由肝脏从胆固醇合成，通过肠道微生物群沿着肠道进行沿着化学转化，这些转化的产物通过宿主受体发出信号，影响宿主的整体健康。这些转化包括胆汁酸去缀合、氧化和7 α-脱羟基化。了解肠道中胆汁酸转化的代谢是至关重要的，因为去缀合是7 α-脱羟基的先决条件，并且因为大多数肠道微生物具有胆汁酸转化能力。在这里，我们使用了一个耦合的代谢组学和元蛋白质组学的方法来探测在gnotobiotic小鼠模型的肠道微生物群落的体内活性。结果显示，Clostridium dens参与7 α-脱羟基作用，Muribaculum和Bacteroides参与解偶联作用，另外6种生物参与氧化作用（Clostridium、Muribaculum、Bacteroides、Bifidobacterium、Acutalibacter和Akkermansia）。此外，考虑了具有更复杂的微生物群、生态失调的微生物群或没有微生物群的小鼠中的胆汁酸谱。例如，常规小鼠具有多种多样的胆汁酸，但用抗生素如克林霉素治疗导致7 α-脱羟基化的完全抑制，强调了该化合物对能够进行该过程的生物体的强烈抑制。最后，将肝胆汁酸池大小作为微生物群的函数进行比较，发现减少的微生物群影响宿主信号传导，但不一定影响胆汁酸合成。在这项研究中，胆汁酸转化映射到相关的活性微生物，提供了微生物群和胆汁酸组成之间的关系的系统表征。
Bile acids, which are synthesized from cholesterol by the liver, are chemically transformed along the intestinal tract by the gut microbiota, and the products of these transformations signal through host receptors, affecting overall host health. These transformations include bile acid deconjugation, oxidation, and 7 alpha-dehydroxylation. An understanding of the biogeography of bile acid transformations in the gut is critical because deconjugation is a prerequisite for 7 alpha-dehydroxylation and because most gut microorganisms harbor bile acid transformation capacity. Here, we used a coupled metabolomic and metaproteomic approach to probe in vivo activity of the gut microbial community in a gnotobiotic mouse model. Results revealed the involvement of Clostridium scindens in 7 alpha-dehydroxylation, of the genera Muribaculum and Bacteroides in deconjugation, and of six additional organisms in oxidation (the genera Clostridium, Muribaculum, Bacteroides, Bifidobacterium, Acutalibacter, and Akkermansia). Furthermore, the bile acid profile in mice with a more complex microbiota, a dysbiosed microbiota, or no microbiota was considered. For instance, conventional mice harbor a large diversity of bile acids, but treatment with an antibiotic such as clindamycin results in the complete inhibition of 7 alpha-dehydroxylation, underscoring the strong inhibition of organisms that are capable of carrying out this process by this compound. Finally, a comparison of the hepatic bile acid pool size as a function of microbiota revealed that a reduced microbiota affects host signaling but not necessarily bile acid synthesis. In this study, bile acid transformations were mapped to the associated active microorganisms, offering a systematic characterization of the relationship between microbiota and bile acid composition.