Perinatal bisphenol‐A exposure causes colonic and liver inflammation in rabbit pups and alters gut bacterial and metabolite profiles

Abstract

Recent evidence suggests that bisphenol‐A (BPA), an environmental endocrine‐disrupter, is present in all the samples of umbilical cord blood obtained from pregnant women. BPA at low doses has been linked to a variety of developmental effects in vivo as well as gut permeability in rodents. We hypothesized that perinatal exposure to BPA elevates colonic inflammation in the offspring by altering gut bacterial and their metabolite profiles. To test this hypothesis, rabbits, that mimic human development with a prolonged infantile period of reproductive differentiation, were exposed to either vehicle or BPA (200 µg/kg/d) orally from day 15 of pregnancy until delivery. After 6 wks, distal colon and liver samples from rabbit pups were analyzed for histological inflammation and metabolite profiles (LC‐MS/MS). Cecal samples were analyzed for gut bacteria (16S rRNA sequencing). Perinatal BPA elevated (p 蠄 0.05) intestinal and liver histological inflammation scores based on neutrophil, eosinophil, and lymphocyte infiltration compared to control pups. Untargeted metabolomics revealed that intestinal and liver metabolites were significantly different between BPA and controls. Global gut bacterial profiles were altered with perinatal BPA exposure. In particular, the abundance of Akkermansia spp. and Bacteroidetes spp. were reduced (p 蠄 0.05) with BPA exposure. These results suggest that perinatal BPA exposure induces colonic and liver inflammation and concomitantly alters gut bacterial and metabolite profiles.