早年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。
Sex-Dependent Effects of Cadmium Exposure in Early Life on Gut Microbiota and Fat Accumulation in Mice.
作者信息
Ba Qian, Li Mian, Chen Peizhan, Huang Chao, Duan Xiaohua, Lu Lijun, Li Jingquan, Chu Ruiai, Xie Dong, Song Haiyun, Wu Yongning, Ying Hao, Jia Xudong, Wang Hui
机构信息
Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
出版信息
Environ Health Perspect. 2017 Mar;125(3):437-446. doi: 10.1289/EHP360. Epub 2016 Sep 16.
BACKGROUND
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.
OBJECTIVES
We investigated the effects of early exposure to cadmium, at an environmentally relevant dosage, on adult metabolism and the mechanism of action.
METHODS
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.
RESULTS
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.
CONCLUSIONS
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. Citation: 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.
背景
环境镉污染因饮食中镉的平均摄入量较高，对公众健康构成严重风险。然而，不同生命阶段环境镉暴露对健康的长期影响仍不明确。
目的
我们研究了在与环境相关剂量下，早期镉暴露对成年代谢的影响及其作用机制。
方法
我们建立了生命早期低剂量镉（LDC）暴露的小鼠模型，以研究长期的代谢后果。通过16S rDNA测序、微生物生态分析和粪便微生物群移植来测量肠道菌群，以探索潜在的作用机制。
结果
生命早期低剂量镉（100 nM）暴露导致成年雄性小鼠脂肪堆积。肝脏基因分析显示脂肪酸和脂质代谢过程增强。低剂量镉使肠道微生物群受到干扰，导致多样性降低和组成改变。时间序列研究表明，生命早期阶段，尤其是8周龄时的肠道菌群对低剂量镉敏感，这一时期的改变可能导致成年期肥胖，即使微生物群后来恢复。通过微生物群移植和清除实验进一步证实了肠道细菌在低剂量镉诱导的脂肪堆积中的重要性。此外，仅在雄性而非雌性小鼠中观察到低剂量镉的代谢影响。
结论
生命早期阶段环境剂量的镉会导致肠道微生物群改变，加速肝脏脂质代谢，并以性别依赖的方式导致终身代谢后果。这些发现有助于更好地理解环境中镉的健康风险。引用文献：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年。生命早期镉暴露对小鼠肠道微生物群和脂肪堆积的性别依赖性影响。《环境健康展望》125:437 - 446；http://dx.doi.org/10.1289/EHP360 。
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