膳食抗氧化剂麦角硫因的微生物转运体

2022-12-07 17:28

总的来说，我们的研究结果说明了以前未被重视的肠道微生物氧化还原调节机制，并表明饮食 EGT 间竞争可能广泛地影响着人类健康。

SCI 6 December 2022

A microbial transporter of the dietary antioxidant ergothioneine

（Cell；IF:66.85）

Dumitrescu DG, Gordon EM, Kovalyova Y, et al. A microbial transporter of the dietary antioxidant ergothioneine. Cell. 2022

CORRESPONDENCE TO : stavroula.hatzios@yale.edu

Abstract 摘要

Low-molecular-weight (LMW) thiols are small-molecule antioxidants required for the maintenance of intracellular redox homeostasis. However, many host-associated microbes, including the gastric pathogen Helicobacter pylori, unexpectedly lack LMW-thiol biosynthetic pathways. Using reactivity-guided metabolomics, we identified the unusual LMW thiol ergothioneine (EGT) in H. pylori. Dietary EGT accumulates to millimolar levels in human tissues and has been broadly implicated in mitigating disease risk. Although certain microorganisms synthesize EGT, we discovered that H. pylori acquires this LMW thiol from the host environment using a highly selective ATP-binding cassette transporter-EgtUV. EgtUV confers a competitive colonization advantage in vivo and is widely conserved in gastrointestinal microbes. Furthermore, we found that human fecal bacteria metabolize EGT, which may contribute to production of the disease-associated metabolite trimethylamine N-oxide. Collectively, our findings illustrate a previously unappreciated mechanism of microbial redox regulation in the gut and suggest that inter-kingdom competition for dietary EGT may broadly impact human health.

低分子量 (LMW) 硫醇是维持细胞内氧化还原稳态所需的小分子抗氧化剂。然而，许多宿主相关微生物，包括胃病原体幽门螺杆菌，出乎意料地缺乏 LMW-硫醇生物合成途径。通过反应性指导的代谢组学，我们在幽门螺杆菌中发现了不寻常的 LMW 硫醇麦角硫因 (EGT)。饮食中的 EGT 在人体组织中能够积累到毫摩尔水平，并广泛参与疾病风险的减轻。尽管某些微生物合成 EGT，但我们发现幽门螺杆菌使用高度选择性的 ATP 结合盒转运蛋白-EgtUV 从宿主环境中获取这种 LMW 硫醇。EgtUV 在体内具有竞争性定植优势，在胃肠道微生物中广泛保留。此外，我们发现人类粪便细菌能够代谢 EGT，这可能有助于产生与疾病相关的代谢物三甲胺 N-氧化物。总的来说，我们的研究结果说明了以前未被重视的肠道微生物氧化还原调节机制，并表明饮食 EGT 间竞争可能广泛地影响着人类健康。