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ORIGINAL RESEARCH article

Front. Endocrinol.
Sec. Translational and Clinical Endocrinology
Volume 15 - 2024 | doi: 10.3389/fendo.2024.1415216
This article is part of the Research Topic Environmental Endocrine Disruptors: Mechanisms, Implications, and Advances in Detection and Mitigation in Endocrinology View all 4 articles

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

Provisionally accepted
Wang Jiaqi Wang Jiaqi 1Ce Su Ce Su 2*Xin Wang Xin Wang 1*Yangcheng Liu Yangcheng Liu 1*Wei Liu Wei Liu 1*Zheng Xiang Zheng Xiang 1*Baoli Xu Baoli Xu 3*Mingqin Qian Mingqin Qian 4*
  • 1 Liaoning University, Shenyang, China
  • 2 Shenyang Tenth People's Hospital, Shenyang, Liaoning Province, China
  • 3 Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning Province, China
  • 4 The People's Hospital of Liaoning Province, Shenyang, Liaoning Province, China

The final, formatted version of the article will be published soon.

    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.

    Keywords: bisphenol A, Gut-liver axis, Toxicity mechanism, intestinal flora, Metabolism

    Received: 10 Apr 2024; Accepted: 30 Jul 2024.

    Copyright: © 2024 Jiaqi, Su, Wang, Liu, Liu, Xiang, Xu and Qian. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Ce Su, Shenyang Tenth People's Hospital, Shenyang, 110044, Liaoning Province, China
    Xin Wang, Liaoning University, Shenyang, China
    Yangcheng Liu, Liaoning University, Shenyang, China
    Wei Liu, Liaoning University, Shenyang, China
    Zheng Xiang, Liaoning University, Shenyang, China
    Baoli Xu, Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning Province, China
    Mingqin Qian, The People's Hospital of Liaoning Province, Shenyang, Liaoning Province, China

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