The gut microbiome is required for full protection against acute arsenic toxicity in mouse models
The gut microbiome is required for full protection against acute arsenic toxicity in mouse models
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DOI：
10.1038/s41467-018-07803-9
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发表时间：
2018-12-21
影响因子：
16.6
通讯作者：
Walk, Seth T.
中科院分区：
文献类型：
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作者：
Coryell, Michael;McAlpine, Mark;Walk, Seth T.
砷通过受污染的食物和饮用水使全世界约2亿人中毒。令人困惑的是，肠道微生物组被认为可以减轻和加剧砷的毒性。在这里，我们表明微生物组保护小鼠免受砷诱导的死亡。与对照组小鼠相比，驱虫组小鼠和无菌组小鼠在粪便中排出的砷较少，在器官中积累的砷较多。与野生型和/或常规对应物相比，缺乏主要砷解毒酶（As 3 mt）的小鼠在抗生素治疗后或当衍生无菌时对砷过敏。人类微生物组（粪便）移植保护无菌As 3 mt-KO小鼠免受砷诱导的死亡，但保护取决于微生物组的稳定性和特定细菌的存在，包括粪杆菌。我们的研究结果表明，功能性As 3 mt和特定的微生物组成员都需要在小鼠模型中保护免受急性砷中毒。我们预计肠道微生物组将成为人类疾病（砷中毒）发病率的重要解释因素，以及预防和治疗策略的新目标。
Arsenic poisons an estimated 200 million people worldwide through contaminated food and drinking water. Confusingly, the gut microbiome has been suggested to both mitigate and exacerbate arsenic toxicity. Here, we show that the microbiome protects mice from arsenic-induced mortality. Both antibiotic-treated and germ-free mice excrete less arsenic in stool and accumulate more arsenic in organs compared to control mice. Mice lacking the primary arsenic detoxification enzyme (As3mt) are hypersensitive to arsenic after antibiotic treatment or when derived germ-free, compared to wild-type and/or conventional counterparts. Human microbiome (stool) transplants protect germ-free As3mt-KO mice from arsenic-induced mortality, but protection depends on microbiome stability and the presence of specific bacteria, including Faecalibacterium. Our results demonstrate that both a functional As3mt and specific microbiome members are required for protection against acute arsenic toxicity in mouse models. We anticipate that the gut microbiome will become an important explanatory factor of disease (arsenicosis) penetrance in humans, and a novel target for prevention and treatment strategies.