DataSheet_1_Interactions between arsenic exposure, high-fat diet and NRF2 shape the complex responses in the murine gut microbiome and hepatic metabolism.zip

Inorganic arsenic (iAs) exposure has been associated to various detrimental effects such as development of metabolic syndrome and type 2 diabetes via oxidative stress and induced prolonged activation of the NRF2 transcription factor. Such effects can be aggravated by poor dietary habits. The role of gut microbiota in promoting metabolic changes in response to arsenic has yet to be precisely defined. To address the complexity of the interactions between diet, NFE2L2/NRF2, and gut microbiota, we studied the chronic effects of iAs exposure in wild-type (WT) and Nrf2-/- mice fed normal (ND) vs. high-fat diet (HFD), on the gut microbial community in the context of hepatic metabolism. We demonstrate that all treatments and interactions influenced bacteria and metabolic profiles, with dietary differences causing a strong overlap of responses between the datasets. By identifying five metabolites of known microbial origin and following their fate across treatments, we provide examples on how gut microbial products can participate in the development of iAs and HFD-induced metabolic disease. Overall, our results underline the importance of the microbial community in driving gut-liver-cross talk during iAs and HFD exposure.

无机砷（iAs）暴露已被证实与多种不良健康效应相关，例如通过氧化应激及诱导核因子E2相关因子2（NRF2）转录因子的持续激活，介导代谢综合征与2型糖尿病的发生发展。不良饮食习惯可进一步加剧上述效应。目前，肠道菌群在介导砷暴露引发代谢改变中的具体作用仍有待精准阐明。为解析饮食、NFE2L2/NRF2与肠道菌群间相互作用的复杂机制，本研究以正常饮食（ND）及高脂饮食（HFD）喂养的野生型（WT）和Nrf2基因敲除（Nrf2-/-）小鼠为模型，探究了无机砷慢性暴露对其肝脏代谢背景下肠道菌群群落的影响。研究表明，所有处理因素及交互作用均会对菌群组成与代谢谱产生影响，且饮食差异会导致不同数据集间的应答反应出现显著重叠。本研究通过鉴定5种已知微生物起源的代谢物，并追踪其在各处理组中的动态变化，为肠道菌群产物如何参与无机砷与高脂饮食诱导的代谢性疾病发生提供了具体例证。综上，本研究结果凸显了肠道菌群群落在无机砷与高脂饮食暴露过程中介导肠-肝轴交互的重要作用。