Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.
Nat Microbiol. 2019 Jan;4(1):155-163. doi: 10.1038/s41564-018-0294-4. Epub 2018 Nov 19.
The essential nutrient choline is metabolized by gut bacteria to the disease-associated metabolite trimethylamine (TMA). However, most of the choline obtained via the diet and present in the human body is incorporated into larger metabolites, including the lipid phosphatidylcholine (PC). Here, we report that many choline-utilizing gut microorganisms can hydrolyse PC using a phospholipase D (PLD) enzyme and further convert the released choline to TMA. Genetic and in vitro characterization of the PLD from Escherichia coli MS 200-1 showed this enzyme is essential for bacterial hydrolysis of PC and prefers this substrate. PLDs are also found in gut bacterial isolates that are unable to convert choline to TMA, suggesting that additional members of the gut microbiota may influence access to this substrate. Unexpectedly, this PLD is only distantly related to characterized PLDs from pathogenic bacteria, suggesting a distinct evolutionary history. Together, these results reveal a previously underappreciated role for gut microorganisms in phospholipid metabolism and a potential target for inhibiting TMA production.
胆碱是一种必需营养素，可被肠道细菌代谢为与疾病相关的代谢物三甲胺（TMA）。然而，人体通过饮食获得的大部分胆碱都被整合到更大的代谢物中，包括脂质磷脂酰胆碱（PC）。在这里，我们报告说，许多利用胆碱的肠道微生物可以使用磷脂酶 D（PLD）酶水解 PC，并进一步将释放的胆碱转化为 TMA。对大肠杆菌 MS 200-1 的 PLD 的遗传和体外特性分析表明，该酶对细菌水解 PC 是必需的，并且优先作用于该底物。在无法将胆碱转化为 TMA 的肠道细菌分离物中也发现了 PLD，这表明肠道微生物组的其他成员可能会影响对该底物的利用。出乎意料的是，这种 PLD 与来自病原菌的已鉴定的 PLD 关系疏远，表明其具有独特的进化历史。总之，这些结果揭示了肠道微生物在磷脂代谢中的先前被低估的作用，以及抑制 TMA 产生的潜在靶点。
