Sex-Dependent Effects of Cadmium Exposure in Early Life on Gut Microbiota and Fat Accumulation in Mice.
Sex-Dependent Effects of Cadmium Exposure in Early Life on Gut Microbiota and Fat Accumulation in Mice.
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DOI：
10.1289/ehp360
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发表时间：
2017-03
影响因子：
10.4
通讯作者：
Wang H
中科院分区：
文献类型：
--
作者：
Ba Q;Li M;Chen P;Huang C;Duan X;Lu L;Li J;Chu R;Xie D;Song H;Wu Y;Ying H;Jia X;Wang H
环境中镉的平均膳食摄入量很高，是一个严重的公共健康风险。然而，在不同的生命阶段环境中暴露于镉的长期健康影响仍不清楚。我们研究了早期暴露于镉，在环境相关剂量，对成人代谢和作用机制的影响。我们建立了低剂量镉（LDC）暴露在生命早期的小鼠模型，以检查长期代谢的后果。通过16 S rDNA测序、微生物生态学分析和粪便微生物群移植进行肠道植物群测量以探索潜在的潜在机制。早期LDC暴露（100 nM）导致成年雄性小鼠脂肪蓄积。肝脏基因表达谱显示脂肪酸和脂质代谢过程升高。肠道微生物群受到LDC的干扰，导致多样性减少和组成改变。时间序列研究表明，肠道植物群在生命早期阶段，特别是在8周时，易受LDC的影响，并且即使微生物群后来恢复，在此期间的改变也可能导致成年肥胖。通过微生物群移植和去除实验进一步证实了肠道细菌在LDC诱导的脂肪积累中的重要性。此外，仅在雄性而非雌性小鼠中观察到LDC的代谢效应。在生命的早期阶段，镉的环境剂量会导致肠道微生物群的改变，加速肝脏脂质代谢，并以性别依赖的方式导致终身代谢的后果。这些发现使人们更好地了解环境中镉的健康风险。Ba Q，Li M，Chen P，Huang C，Duan X，Lu L，Li J，Chu R，Xie D，Song H，Wu Y，Ying H，Jia X，Wang H. 2017.早期镉暴露对小鼠肠道微生物群和脂肪积累的性别依赖性影响。环境健康展望125：437-446; http：dx.doi.org/10.1289/EHP360
Environmental cadmium, with a high average dietary intake, is a severe public health risk. However, the long-term health implications of environmental exposure to cadmium in different life stages remain unclear. We investigated the effects of early exposure to cadmium, at an environmentally relevant dosage, on adult metabolism and the mechanism of action. We established mouse models with low-dose cadmium (LDC) exposure in early life to examine the long-term metabolic consequences. Intestinal flora measurement by 16S rDNA sequencing, microbial ecological analyses, and fecal microbiota transplant was conducted to explore the potential underlying mechanisms. Early LDC exposure (100 nM) led to fat accumulation in adult male mice. Hepatic genes profiling revealed that fatty acid and lipid metabolic processes were elevated. Gut microbiota were perturbed by LDC to cause diversity reduction and compositional alteration. Time-series studies indicated that the gut flora at early-life stages, especially at 8 weeks, were vulnerable to LDC and that an alteration during this period could contribute to the adult adiposity, even if the microbiota recovered later. The importance of intestinal bacteria in LDC-induced fat accumulation was further confirmed through microbiota transplantation and removal experiments. Moreover, the metabolic effects of LDC were observed only in male, but not female, mice. An environmental dose of cadmium at early stages of life causes gut microbiota alterations, accelerates hepatic lipid metabolism, and leads to life-long metabolic consequences in a sex-dependent manner. These findings provide a better understanding of the health risk of cadmium in the environment. Ba Q, Li M, Chen P, Huang C, Duan X, Lu L, Li J, Chu R, Xie D, Song H, Wu Y, Ying H, Jia X, Wang H. 2017. Sex-dependent effects of cadmium exposure in early life on gut microbiota and fat accumulation in mice. Environ Health Perspect 125:437–446; http://dx.doi.org/10.1289/EHP360