title: Sex-Dependent Effects of Cadmium Exposure in Early Life on Gut Microbiota and Fat Accumulation in Mice.
abstract: 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. 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.
authors.affiliation: Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Ba
authors.forename: Mian
authors.initials: M
authors.lastname: Li
authors.forename: Peizhan
authors.initials: P
authors.lastname: Chen
authors.forename: Chao
authors.initials: C
authors.lastname: Huang
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Duan
authors.forename: Lijun
authors.initials: L
authors.lastname: Lu
authors.forename: Jingquan
authors.initials: J
authors.lastname: Li
authors.forename: Ruiai
authors.initials: R
authors.lastname: Chu
authors.forename: Dong
authors.initials: D
authors.lastname: Xie
authors.forename: Haiyun
authors.initials: H
authors.lastname: Song
authors.forename: Yongning
authors.initials: Y
authors.lastname: Wu
authors.forename: Hao
authors.initials: H
authors.lastname: Ying
authors.forename: Xudong
authors.initials: X
authors.lastname: Jia
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
mesh_terms: D050154:Adiposity; D000818:Animals; D002104:Cadmium / Q000633:toxicity*; D000069196:Gastrointestinal Microbiome / Q000187:drug effects*; D015386:Hazardous Substances / Q000633:toxicity*; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism; D051379:Mice; D009765:Obesity / Q000378:metabolism
chemical_list: D015386:Hazardous Substances; D002104:Cadmium