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母体暴露于农药会导致母体和后代的肠道微生物群和血脑屏障紊乱,而这种紊乱可以被一种益生元预防。

Maternal exposure to pesticides induces perturbations in the gut microbiota and blood-brain barrier of dams and the progeny, prevented by a prebiotic.

机构信息

PERITOX-Périnatalité et Risques Toxiques-UMR_I 01 UPJV/INERIS, Centre Universitaire de Recherche en Santé, CURS-UPJV, University of Picardie Jules Verne, CEDEX 1, 80054, Amiens, France.

Laboratoire de La Barrière Hémato-Encéphalique (LBHE), UR 2465, University of Artois, 62300, Lens, France.

出版信息

Environ Sci Pollut Res Int. 2024 Oct;31(49):58957-58972. doi: 10.1007/s11356-024-34969-1. Epub 2024 Sep 26.

Abstract

Exposure to pesticide residues during the first 1000 days of life can disrupt body homeostasis and contribute to chronic metabolic diseases. Perinatal chlorpyrifos (CPF) exposure alters gut microbiota (GM) balance, potentially affecting offspring's health. Given the GM influence on brain function, the primary aim is to determine if pesticide-induced dysbiosis (microbial imbalance) affects indirectly other organs, such as the blood-brain barrier (BBB). The secondary objective is to evaluate the prebiotics protective effects, particularly inulin in promoting microbial balance (symbiosis), in both mothers and offspring. A total of 15 or more female rats were divided in 4 groups: control, oral CPF-exposed (1 mg/kg/day), exposed to inulin (10 g/L), and co-exposed to CPF and inulin from pre-gestation until weaning of pups. Samples from intestines, spleen, liver, and brain microvessels underwent microbiological and biomolecular analyses. Bacterial culture assessed GM composition of living bacteria and their translocation to non-intestinal organs. RT qPCR and Western blotting detected gene expression and protein levels of tight junction markers in brain microvessels. CPF exposure caused gut dysbiosis in offspring, with decreased Lactobacillus and Bifidobacterium and increased Escherichia coli (p < 0.01) leading to bacterial translocation to the spleen and liver. CPF also decreased tight junction's gene expression levels (50 to 60% decrease of CLDN3, p < 0.05). In contrast, inulin partially mitigated these adverse effects and restored gene expression to control levels. Our findings demonstrate a causal link between GM alterations and BBB integrity disruptions. The protective effects of inulin suggest potential therapeutic strategies to counteract pesticide-induced dysbiosis.

摘要

生命最初 1000 天接触农药残留会破坏体内平衡,导致慢性代谢疾病。围产期氯吡硫磷(CPF)暴露会改变肠道微生物群(GM)平衡,可能影响后代健康。鉴于 GM 对大脑功能的影响,主要目的是确定农药诱导的生态失调(微生物失衡)是否会间接影响其他器官,如血脑屏障(BBB)。次要目标是评估益生菌的保护作用,特别是菊糖在促进微生物平衡(共生)方面,在母亲和后代中的作用。总共将 15 只或更多只雌性大鼠分为 4 组:对照组、口服 CPF 暴露组(1mg/kg/天)、暴露于菊糖组(10g/L)和 CPF 和菊糖共同暴露组,从受孕前到幼崽断奶。肠道、脾脏、肝脏和脑微血管样本进行微生物学和生物分子分析。细菌培养评估活细菌的 GM 组成及其向非肠道器官的易位。RT-qPCR 和 Western blot 检测脑微血管中紧密连接标记物的基因表达和蛋白水平。CPF 暴露导致后代肠道生态失调,乳杆菌和双歧杆菌减少,大肠杆菌增加(p<0.01),导致细菌易位到脾脏和肝脏。CPF 还降低了紧密连接的基因表达水平(CLDN3 降低 50%至 60%,p<0.05)。相比之下,菊糖部分减轻了这些不利影响,并将基因表达恢复到对照水平。我们的研究结果表明 GM 改变与 BBB 完整性破坏之间存在因果关系。菊糖的保护作用表明,可能有对抗农药诱导的生态失调的治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/73fb/11513755/6657cfb96c60/11356_2024_34969_Fig1_HTML.jpg

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