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慢性接触毒死蜱对大鼠激素、炎症和肠道微生物群的年龄和饮食特异性影响。

Age- and diet-specific effects of chronic exposure to chlorpyrifos on hormones, inflammation and gut microbiota in rats.

机构信息

Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China.

Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China.

出版信息

Pestic Biochem Physiol. 2019 Sep;159:68-79. doi: 10.1016/j.pestbp.2019.05.018. Epub 2019 May 27.

DOI:10.1016/j.pestbp.2019.05.018
PMID:31400786
Abstract

Chlorpyrifos is a pesticide frequently detected in food and has been reported to disturb endocrine and gut health, which was regulated by gut microbiota and enteroendocrine cells. In this study, newly weaned (3 week) and adult (8 week) male rats fed a normal- or high- fat diet were chronically exposed to 0.3 mg chlorpyrifos/kg bodyweight/day. The effects of chlorpyrifos exposure on serum hormone levels, proinflammatory cytokines and gut microbiota were evaluated. Chronic exposure to chlorpyrifos significantly decreased the concentrations of luteinizing hormone, follicule stimulating hormone and testosterone, which was found only in the normal-fat diet. The counteracted effect of high-fat diet was also found in gut hormones and proinflammatory cytokines. Significantly higher concentrations of glucagon-like peptide-1, pancreatic polypeptide, peptide tyrosine tyrosine (PYY), ghrelin, gastric inhibitory poly-peptide, IL-6, monocyte chemoattractant protein-1, and TNF-α were found in rats exposed to chlorpyrifos beginning at newly weaned, whereas only the PYY, ghrelin and IL-6 concentrations increased significantly in rats exposed in adulthood. Furthermore, a decrease in epinephrine induced by chlorpyrifos exposure was found in rats exposed to chlorpyrifos beginning at newly weaned, regardless of their diet. Chlorpyrifos-induced disturbances in the microbiome community structure were more apparent in rats fed a high-fat diet and exposed beginning at newly weaned. The affected bacteria included short-chain fatty acid-producing bacteria (Romboutsia, Turicibacter, Clostridium sensu stricto 1, norank_f_Coriobacteriaceae, Faecalibaculum, Parasutterella and norank_f__Erysipelotrichaceae), testosterone-related genus (Turicibacter, Brevibacterium), pathogenic bacteria (Streptococcus), and inflammation-related bacteria (unclassified_f__Ruminococcaceae, Ruminococcaceae_UCG-009, Parasutterella, Oscillibacter), which regulated the endocrine system via the hypothalamic-pituitary-adrenal axis, as well as the immune response and gut barrier. Early exposure accelerated the endocrine-disturbing effect and immune responses of chlorpyrifos, although these effects can be eased or recovered by a high-fat diet. This study helped clarify the relationship between disrupted endocrine function and gut microbiota dysbiosis induced by food contaminants such as pesticides.

摘要

毒死蜱是一种经常在食物中检测到的农药,据报道,它会干扰内分泌和肠道健康,而这两者是由肠道微生物群和肠内分泌细胞调节的。在这项研究中,我们新发现,慢性暴露于 0.3mg/kg 体重/天的毒死蜱会显著降低血清促黄体生成素、促卵泡生成素和睾酮的浓度,这种作用仅在正常脂肪饮食中观察到。高脂肪饮食也会对肠道激素和促炎细胞因子产生拮抗作用。在新断奶的大鼠中,发现暴露于毒死蜱会导致胰高血糖素样肽-1、胰多肽、肽酪氨酸酪氨酸(PYY)、胃饥饿素、胃抑制多肽、IL-6、单核细胞趋化蛋白-1 和 TNF-α的浓度显著升高,而只有在成年期暴露于毒死蜱的大鼠中发现 PYY、胃饥饿素和 IL-6 的浓度显著升高。此外,无论饮食如何,新断奶大鼠暴露于毒死蜱后,肾上腺素的分泌也会减少。在高脂肪饮食和新断奶开始暴露于毒死蜱的大鼠中,毒死蜱引起的微生物群落结构紊乱更为明显。受影响的细菌包括短链脂肪酸产生菌(Romboutsia、Turicibacter、Clostridium sensu stricto 1、norank_f_Coriobacteriaceae、Faecalibaculum、Parasutterella 和 norank_f__Erysipelotrichaceae)、与睾酮相关的属(Turicibacter、Brevibacterium)、病原菌(Streptococcus)和与炎症相关的细菌(unclassified_f__Ruminococcaceae、Ruminococcaceae_UCG-009、Parasutterella、Oscillibacter),它们通过下丘脑-垂体-肾上腺轴调节内分泌系统,以及免疫反应和肠道屏障。早期暴露加速了毒死蜱的内分泌干扰作用和免疫反应,尽管高脂肪饮食可以缓解或恢复这些作用。本研究有助于阐明食物污染物(如农药)引起的内分泌功能紊乱与肠道微生物群失调之间的关系。

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