Integrated metagenomics identifies a crucial role for trimethylamine-producing Lachnoclostridium in promoting atherosclerosis.
Integrated metagenomics identifies a crucial role for trimethylamine-producing Lachnoclostridium in promoting atherosclerosis.
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DOI：
10.1038/s41522-022-00273-4
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发表时间：
2022-03-10
影响因子：
9.2
通讯作者：
Li J
中科院分区：
文献类型：
--
作者：
Cai YY;Huang FQ;Lao X;Lu Y;Gao X;Alolga RN;Yin K;Zhou X;Wang Y;Liu B;Shang J;Qi LW;Li J
微生物三甲胺裂解酶通过生成三甲胺(TMA)的前体三甲胺(TMA)裂解酶促进动脉粥样硬化的发展。TMAO有很好的记录，但产生TMA的细菌就不能说同样的话了。这项工作旨在确定人类肠道微生物区系中产生TMA的属。我们从人类微生物组计划数据库中检索了人类相关微生物的基因组，包括1751个基因组，统一的人类胃肠道基因组集，包括4644个肠道原核生物，概括了4930个物种水平的基因组库，以及来自11个种群的2134个个体的公共肠道元基因组数据。通过序列搜索，发现102属216种含有TMA裂解酶的细菌含有CNTA/B、YAW/X和/或CutC/D同源序列。用CNTA序列鉴定了5属13株细菌，用CutC序列鉴定了14属30株细菌，在健康个体中检测到相对丰度。发现动脉粥样硬化症患者体内含CuT C最丰富的两个属--衣原体(p = 2.9e−05)和梭状芽胞杆菌(p = 5.8e−04)的含量明显高于健康人。在胆碱(底物)作用下，溶糖乳杆菌有效地将其转化为TMA，转化率高于98.7%，而产孢链霉菌的转化率为63.8-67.5%。体内研究进一步表明，糖链霉菌和胆碱可促进载脂蛋白E−/−小鼠血清TMAO水平显著升高，并伴有明显的主动脉斑块积聚。本研究揭示了肠道细菌Lsc在将胆碱转化为TMA从而促进动脉粥样硬化的发展中的意义和效率。
Microbial trimethylamine (TMA)-lyase activity promotes the development of atherosclerosis by generating of TMA, the precursor of TMA N-oxide (TMAO). TMAO is well documented, but same can not be said of TMA-producing bacteria. This work aimed to identify TMA-producing genera in human intestinal microbiota. We retrieved the genomes of human-associated microorganisms from the Human Microbiome Project database comprising 1751 genomes, Unified Human Gastrointestinal Genome collection consisting 4644 gut prokaryotes, recapitulated 4930 species-level genome bins and public gut metagenomic data of 2134 individuals from 11 populations. By sequence searching, 216 TMA-lyase-containing species from 102 genera were found to contain the homologous sequences of cntA/B, yeaW/X, and/or cutC/D. We identified 13 strains from 5 genera with cntA sequences, and 30 strains from 14 genera with cutC showing detectable relative abundance in healthy individuals. Lachnoclostridium (p = 2.9e−05) and Clostridium (p = 5.8e−04), the two most abundant cutC-containing genera, were found to be much higher in atherosclerotic patients compared with healthy persons. Upon incubation with choline (substrate), L. saccharolyticum effectively transformed it to TMA at a rate higher than 98.7% while that for C. sporogenes was 63.8–67.5% as detected by liquid chromatography-triple quadrupole mass spectrometry. In vivo studies further showed that treatment of L. saccharolyticum and choline promoted a significant increase in TMAO level in the serum of ApoE−/− mice with obvious accumulation of aortic plaque in same. This study discloses the significance and efficiency of the gut bacterium L. saccharolyticum in transforming choline to TMA and consequently promoting the development of atherosclerosis.
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影响因子：
14.8
作者：
Kelley LA;Mezulis S;Yates CM;Wass MN;Sternberg MJ
通讯作者：
Sternberg MJ
影响因子：
28.3
作者：
Kasahara K;Krautkramer KA;Org E;Romano KA;Kerby RL;Vivas EI;Mehrabian M;Denu JM;Bäckhed F;Lusis AJ;Rey FE
通讯作者：
Rey FE
DOI：
10.1073/pnas.1215689109
发表时间：
2012-12-26
影响因子：
11.1
作者：
Craciun, Smaranda;Balskus, Emily P.
通讯作者：
Balskus, Emily P.
影响因子：
3
作者：
Morris, Garrett M.;Huey, Ruth;Lindstrom, William;Sanner, Michel F.;Belew, Richard K.;Goodsell, David S.;Olson, Arthur J.
通讯作者：
Olson, Arthur J.
影响因子：
4.8
作者：
Gregory, Jill C.;Buffa, Jennifer A.;Hazen, Stanley L.
通讯作者：
Hazen, Stanley L.