Discovery of the gut microbial enzyme responsible for bilirubin reduction to urobilinogen.
Discovery of the gut microbial enzyme responsible for bilirubin reduction to urobilinogen.
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发现负责将胆红素还原为尿胆原的肠道微生物酶。
DOI：
10.1101/2023.02.07.527579
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Jiang,Xiaofang
中科院分区：
文献类型：
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作者：
Hall,Brantley;Levy,Sophia;Dufault-Thompson,Keith;Ndjite,GloryMinabou;Weiss,Ashley;Braccia,Domenick;Jenkins,Conor;Yang,Yiyan;Arp,Gabi;Abeysinghe,Stephenie;Jermain,Madison;Wu,ChihHao;Jiang,Xiaofang
血红素的降解及其分解代谢衍生物胆红素在人类与其肠道微生物群之间的相互作用是人类健康的一个重要方面。然而，假设的将胆红素还原为尿胆素原的细菌酶（该途径产生可排泄废物的关键步骤）仍未得到证实。在这项研究中，我们结合生化分析和比较基因组学来鉴定一种新型酶 BilR，它可以将胆红素还原为尿胆素原。我们通过鉴定活性位点中对胆红素减少至关重要的关键残基，从老黄酶家族的其他成员中描绘了 BilR 序列，并发现 BilR 主要由肠道微生物组中的厚壁菌门编码。我们对人类肠道宏基因组的分析表明，BilR 是健康成年人微生物组的一个共同特征，但在新生儿和 IBD 患者中的患病率较低。这一发现为肠道微生物组在胆红素代谢中的作用提供了新的线索，并强调了肠-肝轴在维持胆红素稳态中的重要性。
The degradation of heme and the interplay of its catabolic derivative, bilirubin, between humans and their gut microbiota is an essential facet of human health. However, the hypothesized bacterial enzyme that reduces bilirubin to urobilinogen, a key step that produces the excretable waste products of this pathway, has remained unidentified. In this study, we used a combination of biochemical analyses and comparative genomics to identify a novel enzyme, BilR, that can reduce bilirubin to urobilinogen. We delineated the BilR sequences from other members of the Old Yellow Enzyme family through the identification of key residues in the active site that are critical for bilirubin reduction and found that BilR is predominantly encoded by Firmicutes in the gut microbiome. Our analysis of human gut metagenomes showed that BilR is a common feature of a healthy adult human microbiome but has a decreased prevalence in neonates and IBD patients. This discovery sheds new light on the role of the gut microbiome in bilirubin metabolism and highlights the significance of the gut-liver axis in maintaining bilirubin homeostasis.