Bisphenol A (BPA) is an industrial plasticizer widely found in consumer products such as plastic bottles and canned foods. Human and murine studies have shown strong associations between prenatal exposures to endocrine disruptors such as BPA during early development and the prevalence of various diseases including cardiovascular diseases, type 2 diabetes, and obesity. Previous studies have found that the liver tissue is a sensitive BPA target site, and BPA alters the microbial diversity in exposed mice. To understand whether and how the gut microbiome mediates the effects of BPA on liver gene expression to influence metabolic phenotypes, we conducted a multi-dimensional systems biology study. We treated pregnant C57BL/6 mice with a low dose of BPA at 5ug/kg/day during gestation and evaluated metabolic phenotypes, fecal microbial composition and liver transcriptome of both male and female offspring. Prenatal exposure to low dose BPA significantly not only affected liver genes involved in oxidative phosphorylation, PPAR signaling and fatty acid metabolism, but also affected the gut microbial composition in an age-dependent manner, with the most pronounced effect observed at week 20. Bacteria belonging to the S24-7 and Lachnospiraceae families were correlated to offspring body weight and differentially expressed liver genes such as Fabp1, Acadl and Dgat1. This study provides insights into the relationship between gut bacteria and host liver genes that could contribute to metabolic disease risks upon BPA exposure. Future studies will test whether the gut microbiota identified in this study play a direct causal role on the host genomic and phenotypic responses using fecal transplant and bacteria colonization experiments.


G. Diamante: None. I.C. Cely: None. J. Lang: None. A. Bline: None. Z.O. Zamora: None. M. Singh: None. A. Lusis: None. X. Yang: None.


American Diabetes Association (1-19-PDF-007-R to G.D.)

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at