Research Center for Drug Discovery, Faculty of Pharmacy and Graduate School of Pharmaceutical Science, Keio University.
Division of Biochemistry, Faculty of Pharmacy and Graduate School of Pharmaceutical Science, Keio University.
J Toxicol Sci. 2021;46(2):91-97. doi: 10.2131/jts.46.91.
Methylmercury (MeHg), an environmental electrophile, binds covalently to the cysteine residues of proteins in organs, altering protein function and causing cytotoxicity. MeHg has also been shown to alter the composition of gut microbes. The gut microbiota is a complex community, the disturbance of which has been linked to the development of certain diseases. However, the relationship between MeHg and gut bacteria remains poorly understood. In this study, we showed that MeHg binds covalently to gut bacterial proteins via cysteine residues. We examined the effects of MeHg on the growth of selected Lactobacillus species, namely, L. reuteri, L. gasseri, L. casei, and L. acidophilus, that are frequently either positively or negatively correlated with human diseases. The results revealed that MeHg inhibits the growth of Lactobacillus to varying degrees depending on the species. Furthermore, the growth of L. reuteri, which was inhibited by MeHg exposure, was restored by NaS treatment. By comparing mice with and without gut microbiota colonization, we found that gut bacteria contribute to the production of reactive sulfur species such as hydrogen sulfide and hydrogen persulfide in the gut. We also discovered that the removal of gut bacteria accelerated accumulation of mercury in the cerebellum, liver, and lungs of mice subsequent to MeHg exposure. These results accordingly indicate that MeHg is captured and inactivated by the hydrogen sulfide and hydrogen persulfide produced by intestinal microbes, thereby providing evidence for the role played by gut microbiota in reducing MeHg toxicity.
甲基汞（MeHg）是一种环境亲电试剂，可通过半胱氨酸残基与器官中的蛋白质共价结合，改变蛋白质功能并导致细胞毒性。MeHg 还被证明会改变肠道微生物的组成。肠道微生物群是一个复杂的群落，其紊乱与某些疾病的发展有关。然而，MeHg 与肠道细菌之间的关系仍知之甚少。在这项研究中，我们表明 MeHg 通过半胱氨酸残基与肠道细菌蛋白共价结合。我们研究了 MeHg 对选定的乳杆菌属物种（即 L. reuteri、L. gasseri、L. casei 和 L. acidophilus）生长的影响，这些细菌通常与人类疾病呈正相关或负相关。结果表明，MeHg 会根据物种的不同，在不同程度上抑制乳杆菌的生长。此外，暴露于 MeHg 会抑制 L. reuteri 的生长，而 NaS 处理可恢复其生长。通过比较有和没有肠道微生物定植的小鼠，我们发现肠道细菌有助于在肠道中产生活性硫物种，如硫化氢和过硫化氢。我们还发现，去除肠道细菌会加速 MeHg 暴露后小鼠小脑、肝脏和肺部汞的积累。这些结果表明，MeHg 被肠道微生物产生的硫化氢和过硫化氢捕获和失活，从而为肠道微生物群在降低 MeHg 毒性方面的作用提供了证据。
