Chen Yi-Ran, Chen Li-Dan, Zheng Lin-Jie
Institute of Public Health, Guangzhou Medical University & Guangzhou Center for Disease Control and Prevention (Guangzhou Health Supervision institute), Guangzhou, 510440, China.
Guangzhou Center for Disease Control and Prevention (Guangzhou Health Supervision institute), Guangzhou, 510440, China.
AMB Express. 2025 Jun 12;15(1):91. doi: 10.1186/s13568-025-01902-9.
Trimethylamine (TMA), produced by gut microbes, is a precursor to a risk factor for cardiovascular diseases. Currently, TMA-degrading bacteria in the human gut have rarely been studied. This study combined TMA-enriched cultures (from 104 young male stool samples) with metagenomic profiling to identify key microbial players of TMA degradation. The results showed that the contribution of Enterococcus to methane metabolism was significantly higher in TMA-enriched culture samples. The 68.58% up-regulation of dmd-tmd (dimethylamine/trimethylamine dehydrogenase) in the TMA-enriched group indicated that the anaerobic dehydrogenase pathway participated in TMA metabolism. Notably, we first identified that taxa containing dmd-tmd belonged to Christensenella timonensis. The up-regulation of genes involved in methanogenesis (M00563) as well as the significant enrichment of M00563 (Reporter Score = 2.223) indicated that the methanogenesis pathway may play a role. We constructed gene databases for genes involved in the anaerobic dehydrogenase pathway (1526 sequences for dmd-tmd, 1319 sequences for mauA, and 326 sequences for mauB, respectively) and the aerobic oxidation pathway (2146 sequences for tmm, 1445 sequences for tdm, and 1519 sequences for dmm, respectively) based on genomes from the Integrated Microbial Genome (IMG) database, most of which belong to Pseudomonadota. Screening gut metagenomes with these databases revealed low sequence identity (< 70%), possibly because of the underrepresentation of gut-specific genomes from IMG. This study links Christensenella timonensis to TMA degradation, providing potential targets for microbiota modulation and a gene-centric framework to advance the characterization of gut microbial TMA metabolism.
由肠道微生物产生的三甲胺（TMA）是心血管疾病风险因素的前体。目前，人类肠道中降解TMA的细菌鲜有研究。本研究将富集TMA的培养物（来自104份年轻男性粪便样本）与宏基因组分析相结合，以确定TMA降解的关键微生物参与者。结果表明，在富集TMA的培养样本中，肠球菌对甲烷代谢的贡献显著更高。富集TMA组中dmd - tmd（二甲胺/三甲胺脱氢酶）上调68.58%，表明厌氧脱氢酶途径参与TMA代谢。值得注意的是，我们首次确定含有dmd - tmd的分类群属于蒂莫内森克里斯滕森菌。参与甲烷生成的基因（M00563）上调以及M00563显著富集（报告分数 = 2.223）表明甲烷生成途径可能发挥作用。我们基于综合微生物基因组（IMG）数据库中的基因组，构建了参与厌氧脱氢酶途径（dmd - tmd的1526个序列、mauA的1319个序列和mauB的326个序列）和好氧氧化途径（tmm的2146个序列、tdm的1445个序列和dmm的1519个序列）的基因数据库，其中大部分属于假单胞菌门。用这些数据库筛选肠道宏基因组发现序列同一性较低（< 70%），这可能是因为IMG中肠道特异性基因组的代表性不足。本研究将蒂莫内森克里斯滕森菌与TMA降解联系起来，为微生物群调节提供了潜在靶点，并提供了一个以基因为中心的框架来推进对肠道微生物TMA代谢的表征。
