College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, 310014, China.
Institute of Translational Medicine, Zhejiang Shuren University, Hangzhou, 310015, China.
Food Chem Toxicol. 2023 Apr;174:113657. doi: 10.1016/j.fct.2023.113657. Epub 2023 Feb 9.
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 F and different developmental stages of F (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 F generations. 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 F and F regenerations. 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.
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疾病，这些疾病风险在后代中仍然存在。在这里，雌性 C57BL/6 小鼠在妊娠期和哺乳期通过饮食补充接受了菌螨威（PRO）（10 和 100mg/kg 体重/天）的口服治疗。然后，我们发现 PRO 改变了 F 代及其不同发育阶段（分别为 7 周和 30 周龄）的 F 代的生理学、肠道屏障和代谢。母体 PRO 暴露影响了小鼠的生长表型和糖脂代谢相关指标和基因，尤其是 F 代的雄性小鼠。胆汁酸（BAs）代谢的变化表明，PRO 通过肠肝循环扰乱了糖脂代谢。此外，PRO 减少了肠道中的粘液分泌，并改变了肠道微生物群的组成，导致更多的细菌在肠道中扩散，并在 F 和 F 代中引发炎症反应。PRO 诱导的肠道微生物群失调与 BAs 代谢物密切相关。总之，这些结果表明，PRO 破坏了肠道屏障的功能完整性，并引发了炎症反应。然后，通过 BAs 肠肝循环诱导糖脂代谢紊乱。本研究表明，PRO 的跨代效应不容忽视。
