黄曲霉毒素B1扰动肠道菌群破坏免疫稳态的机制研究

食品污染物黄曲霉毒素B1(AFB1)是I类致癌物，有强烈的免疫毒性。近年来多项研究表明食物中的AFB1会直接与肠道相互作用，扰动肠道内维持免疫稳态的微生物菌群及其代谢物，这种扰动效应在AFB1免疫毒性中的直接作用及其分子机制尚未阐明。项目前期发现AFB1扰动肠道菌群显著改变菌群结构，导致与免疫系统密切相关的总革兰氏阴性菌及其代谢物脂多糖显著增加，进而促进血液和脾脏炎症因子的显著分泌，同时脾脏相对重量明显增加。为了探究肠道菌群在AFB1破坏免疫稳态中的直接作用，本项目拟利用抗生素处理及AFB1暴露小鼠的粪菌移植，分别抑制和模拟AFB1对肠道菌群的扰动效应，以及精准验证显著差异代谢物，从腹腔巨噬细胞的细胞功能、血清IgA和IgG含量、SIgA分泌水平，综合分析免疫稳态的维持及破坏，从而揭示“AFB1-肠道菌群-免疫紊乱”新效应轴的分子机制，为AFB1解毒提供新靶点。

Aflatoxin B1 (AFB1), common food contaminant, is a class I carcinogen with strong immunotoxicity. Recently, more and more studies have shown that AFB1 in food will directly interact with the intestine and interrupt the gut microbiota, which maintains immune homeostasis. The direct effect of this disturbance on AFB1 immunotoxicity and its molecular mechanism is not yet clarified. In the early stage of the project, it was found that AFB1 perturbed the gut microbiota with the significantly changed structure, resulting in a remarkable increase in the total gram-negative bacteria and their metabolites lipopolysaccharides that are closely related to the immune system. In parallel, the oblivious secretion of inflammatory factors in the blood and spleen was determined. The relative weight of spleen was increased significantly. To explore the direct role of gut microbiota in AFB1-induced immune disorder, this project intends to perform antibiotic treatment or fecal microbiota transplantation in AFB1 exposed mice to inhibit or simulate the disturbance effect of AFB1 on gut microbiota. The difference metabolites were accurately verified as well. The cellular function of peritoneal macrophages, serum IgA and IgG content, SIgA secretion level were used to comprehensive analysis of the maintenance and destruction of immune homeostasis. Thus, the novel effective axis of "AFB1-intestinal flora-immune disorder" was identified here, which could be a potential target for the detoxification of AFB1.