Maternal procymidone exposure has lasting effects on murine gut-liver axis and glucolipid metabolism in offspring
Maternal procymidone exposure has lasting effects on murine gut-liver axis and glucolipid metabolism in offspring
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DOI：
10.1016/j.fct.2023.113657
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发表时间：
2023-02-11
影响因子：
4.3
通讯作者：
Jin，Yuanxiang
中科院分区：
文献类型：
--
作者：
Wang，Xiaofang;Weng，You;Jin，Yuanxiang
越来越多的证据表明，母体暴露于环境污染物会导致肠道和代谢性疾病，这些疾病风险在后代中仍然存在。在此，雌性C57 BL/6小鼠在妊娠期和哺乳期通过饮食补充经口给予腐霉利（PRO）（10和100 mg/kg体重/天）。结果表明，PRO对F0代和F1代不同发育阶段（7周龄和30周龄）的生理、肠道屏障和代谢均有影响。母体PRO暴露对小鼠的生长表型、糖脂代谢相关指标及基因均有影响，尤其是F1代雄性小鼠。胆汁酸（BA）代谢的变化表明PRO通过肝肠循环紊乱糖脂代谢。此外，PRO减少了肠道中的粘液分泌，改变了肠道微生物群的组成，导致更多的细菌在肠道中传播，并在F0和F1再生中引起炎症反应。PRO诱导的肠道菌群失调与BAs代谢产物密切相关。结果表明，PRO破坏了肠屏障的功能完整性，引发了炎症反应。然后通过BA的肠肝循环引起糖脂代谢紊乱。本研究表明，PRO的跨代效应不容忽视。
There is increasing evidence that maternal exposure to environmental pollutants can cause intestinal and metabolic diseases, and these disease risks still exist in offspring. Here, female C57BL/6 mice were orally treated with procymidone (PRO) (10 and 100 mg/kg body weight/day) by dietary supplementation during the gestation and lactation periods. Then, we discovered PRO changed the physiology, intestinal barrier and metabolism both in the generations of F0and different developmental stages of F1(7 weeks and 30 weeks old, respectively). Maternal PRO exposure affected the growth phenotypes and the glucolipid metabolism related indicators and genes of mice, especially the male mice of F1generations. The changes in bile acids (BAs) metabolism demonstrated that PRO disordered glucolipid metabolism through enterohepatic circulation. Furthermore, PRO reduced mucus secretion in the gut and altered the composition of gut microbiota, leading more bacteria to disseminate in the gut and inflammatory responses both in F0and F1regenerations. And PRO-induced gut microbiota dysbiosis was tightly related to BAs metabolites. Together, the results indicated that PRO destructed the functional integrity of intestinal barrier and the inflammatory reaction was triggered. And then, the disorder of glucolipid metabolism was induced through the BAs enterohepatic circulation. This study indicated that the cross-generation effects of PRO could not be ignored.