School of Pharmaceutical Science, Liaoning University, Shenyang, China.
Shenyang Key Laboratory for Causes and Drug Discovery of Chronic Diseases, Shenyang, China.
Front Endocrinol (Lausanne). 2024 Aug 29;15:1415216. doi: 10.3389/fendo.2024.1415216. eCollection 2024.
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.
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 an 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 analyze the related metabolites. The ELISA method was used to assess the levels of serum inflammatory factors.
Histopathological analysis indicated that the 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). Metabolomic analysis of the serum indicated that BPA could regulate 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 in interleukin-6 (IL-6), interleukin-23 (IL-23), and transforming growth factor-β (TGF-β) in the serum of the male-BPA group suggests that BPA exposure affects the immune system.
BPA exposure will cause toxicity to rats via disrupting the gut-liver-hormone axis.
双酚 A（BPA）是一种典型的内分泌干扰物，严重干扰人体内分泌系统，导致生殖障碍和发育异常。然而，其对肠道-肝脏-激素轴的毒性作用尚不清楚。
雄性和雌性大鼠连续 60 天通过口服灌胃暴露于 BPA（300mg/kg）。使用 H&E 染色进行组织病理学评估，并使用自动分析仪测定血清生化指标。使用 16S rRNA 基因测序检测肠道微生物多样性，GC-MS 分析结肠内容物中短链脂肪酸（SCFAs）的含量。使用 UPLC-QTOF MS 分析相关代谢物。使用 ELISA 方法评估血清炎症因子水平。
组织病理学分析表明，BPA 影响肝脏、心脏和睾丸。雄性-BPA 组丙氨酸氨基转移酶（ALT）、甘油三酯（TG）、总胆固醇（TC）和低密度脂蛋白（LDL）水平有显著影响（P<0.05），雌性-BPA 组球蛋白（GLB）、间接胆红素（IBIL）、碱性磷酸酶（ALP）、ALT、TG、TC、高密度脂蛋白（HDL）和肌酐（Cr）水平有显著影响（P<0.05）。宏基因组学（16S rRNA 基因测序）分析表明，BPA 显著降低了大鼠肠道微生物群的多样性并改变了其组成。与对照组和空白组相比，雄性-BPA 组结肠内容物中己酸、异丁酸、异戊酸和丙酸的含量降低（P<0.05），雌性-BPA 组结肠内容物中己酸、异丁酸、异戊酸和缬氨酸的含量降低（P<0.05）。血清代谢组学分析表明，BPA 可以调节胆汁酸水平，特别是熊去氧胆酸（UDCA）及其共轭形式。暴露于 BPA 后，氨基酸、激素和脂质的含量也受到显著影响。雄性-BPA 组血清中白细胞介素 6（IL-6）、白细胞介素 23（IL-23）和转化生长因子-β（TGF-β）的增加表明 BPA 暴露会影响免疫系统。
BPA 暴露会通过破坏肠道-肝脏-激素轴对大鼠造成毒性。
