AUTHOR=Wang Jiaqi , Su Ce , Qian Mingqin , Wang Xin , Chen Changlan , Liu Yangcheng , Liu Wei , Xiang Zheng , Xu Baoli 

TITLE=Subchronic toxic effects of bisphenol A on the gut-liver-hormone axis in rats via intestinal flora and metabolism

JOURNAL=Frontiers in Endocrinology

VOLUME=Volume 15 - 2024

YEAR=2024

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2024.1415216

DOI=10.3389/fendo.2024.1415216

ISSN=1664-2392

ABSTRACT=Background: Bisphenol A (BPA), a characteristic endocrine disruptor, is a substance that seriously interferes with the human endocrine system and causes reproductive disorders and developmental abnormalities. However, its toxic effects on the gut-liver-hormone axis are still unclear. Method: Male and female rats were exposed to BPA (300 mg/kg) by oral gavage for 60 consecutive days. H&E staining was used for histopathological evaluation, and the serum biochemical indexes were determined using automatic analyzer. The 16S rRNA gene sequencing was used to detect the intestinal microbial diversity, and the GC-MS was used to analyze the contents of short-chain fatty acids (SCFAs) in colon contents. UPLC-QTOF MS was used to analysis the related metabolites. ELISA method was used to assess the levels of serum inflammatory factors. Results: Histopathological analysis indicated that liver, heart and testis were affected by BPA. There was a significant effect on alanine aminotransferase (ALT), triglyceride (TG), total cholesterol (TC), and low-density lipoprotein (LDL) in the male-BPA group (P < 0.05), and globulin (GLB), indirect bilirubin (IBIL), alkaline phosphatase (ALP), ALT, TG, TC, high-density lipoprotein (HDL) and  creatinine (Cr) in the female-BPA group (P < 0.05). Metagenomics (16S rRNA gene sequencing) analysis indicated that BPA reduced the diversity and changed the composition of gut microbiota in rats significantly. Compared with the control and blank groups, the contents of caproic acid, isobutyric acid, isovaleric acid and propanoic acid in the colon contents decreased in the male-BPA group (P < 0.05), and caproic acid, isobutyric acid, isovaleric acid and valeric acid in the colon contents decreased in the female-BPA group (P < 0.05). Metabolomics analysis of the serum indicated that BPA could regulated bile acid levels, especially ursodeoxycholic acid (UDCA) and its conjugated forms. The contents of amino acids, hormones and lipids were also significantly affected after exposure to BPA. The increase of IL-6, IL-23 and TGF-β in the serum of male-BPA group suggests that BPA exposure affects the immune system.The BPA exposure will cause toxicity to rats via disrupting the gut-liver-hormone axis.