Fecal Microbiome Composition Does Not Predict Diet-Induced TMAO Production in Healthy Adults.
Fecal Microbiome Composition Does Not Predict Diet-Induced TMAO Production in Healthy Adults.
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DOI：
10.1161/jaha.121.021934
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发表时间：
2021-11-02
影响因子：
5.4
通讯作者：
Tang WHW
中科院分区：
文献类型：
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作者：
Ferrell M;Bazeley P;Wang Z;Levison BS;Li XS;Jia X;Krauss RM;Knight R;Lusis AJ;Garcia-Garcia JC;Hazen SL;Tang WHW
三甲胺-N-氧化物 (TMAO) 是一种小分子，源自肠道微生物对膳食营养素的代谢，会导致心血管疾病。食用红肉后，血浆TMAO 会增加。这种代谢变化被认为部分是由于肠道微生物的扩张，能够利用红肉中丰富的营养物质。我们使用随机交叉研究的数据来估计从粪便微生物组成中估计TMAO的程度。健康参与者接受了一系列 3 种蛋白质来源不同的饮食（红肉、白肉和非肉类），并在接触每种饮食 4 周后收集粪便、血浆和尿液样本。对血浆和尿液中的 TMAO 进行定量，同时对粪便 DNA 进行鸟枪法宏基因组测序。虽然 cai 基因簇与血浆 TMAO 相关性较弱（rho=0.17，P=0.0007），但 TMAO 的弹性网络模型并未因已知有助于 TMAO 合成的细菌基因的丰度而得到改善。对所有分类群、基因和基因家族的全球分析发现，TMAO 没有有意义的预测因子。我们假设与TMAO产生相关的已知基因的丰度不能预测细菌代谢，并且我们在粪便培养过程中测量了胆碱和肉碱三甲胺裂解酶的活性。三甲胺裂解酶基因与其编码的酶的活性仅有微弱的相关性。粪便微生物组组成不能预测全身TMAO，因为在这种情况下，基因拷贝数不能预测细菌代谢活动。网址：https://www.clinicaltrials.gov；唯一标识符：NCT01427855。
Trimethylamine‐N‐oxide (TMAO) is a small molecule derived from the metabolism of dietary nutrients by gut microbes and contributes to cardiovascular disease. Plasma TMAO increases following consumption of red meat. This metabolic change is thought to be partly because of the expansion of gut microbes able to use nutrients abundant in red meat. We used data from a randomized crossover study to estimate the degree to which TMAO can be estimated from fecal microbial composition. Healthy participants received a series of 3 diets that differed in protein source (red meat, white meat, and non‐meat), and fecal, plasma, and urine samples were collected following 4 weeks of exposure to each diet. TMAO was quantitated in plasma and urine, while shotgun metagenomic sequencing was performed on fecal DNA. While the cai gene cluster was weakly correlated with plasma TMAO (rho=0.17, P=0.0007), elastic net models of TMAO were not improved by abundances of bacterial genes known to contribute to TMAO synthesis. A global analysis of all taxonomic groups, genes, and gene families found no meaningful predictors of TMAO. We postulated that abundances of known genes related to TMAO production do not predict bacterial metabolism, and we measured choline‐ and carnitine‐trimethylamine lyase activity during fecal culture. Trimethylamine lyase genes were only weakly correlated with the activity of the enzymes they encode. Fecal microbiome composition does not predict systemic TMAO because, in this case, gene copy number does not predict bacterial metabolic activity. URL: https://www.clinicaltrials.gov; Unique identifier: NCT01427855.