Sex-Dependent Effects of Cadmium Exposure in Early Life on Gut Microbiota and Fat Accumulation in Mice

• Qian Ba ^[1] ; Mian Li ^[1] ; Peizhan Chen ^[1] ; Chao Huang ^[1] ; Xiaohua Duan ^[2] ; Lijun Lu ^[1] ; Jingquan Li ^[1] ; Ruiai Chu ^[1] ; Dong Xie ^[1] ; Haiyun Song ^[1] ; Yongning Wu ^[3] ; Hao Ying ^[1] ; Xudong Jia ^[3] ; Hui Wang ^[4]
  1. [1] Shanghai Institutes for Biological Sciences

     Shanghai Institutes for Biological Sciences

     China

     
  2. [2] ShanghaiTech University

     ShanghaiTech University

     China

     
  3. [3] 2 Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing, China
  4. [4] 1 Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China; 2 Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing, China; 4 Xuhui Central Hospital, Shanghai Clinical Center, Chinese Academy of Sciences, Shanghai, China

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• Localización: Environmental health perspectives, ISSN 0091-6765, Vol. 125, Nº. 3, 2017, págs. 437-446
• Idioma: inglés
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• Resumen

  • 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