Gut microbiota mediated the toxicity of high concentration of dietary nitrite in C57BL/6 mice.
Gut microbiota mediated the toxicity of high concentration of dietary nitrite in C57BL/6 mice.
复制标题
DOI：
10.1016/j.ecoenv.2022.113224
复制
发表时间：
2022-01
影响因子：
6.8
通讯作者：
Jing Xu;Mingzhu Wang;Qiuping Liu;Xiaoying Lin;Kefeng Pu;Zhixing He
中科院分区：
文献类型：
--
作者：
Jing Xu;Mingzhu Wang;Qiuping Liu;Xiaoying Lin;Kefeng Pu;Zhixing He
越来越多的证据表明，长时间接触高水平的亚硝酸盐会对健康产生不利影响。虽然肠道菌群负责亚硝酸盐在肠道中的转化，但肠道菌群是否介导亚硝酸盐的毒性尚缺乏证据。本研究探讨了膳食中亚硝酸盐对雄性C57BL/6小鼠的长期影响，并采用粪便微生物群移植（FMT）来揭示肠道微生物群是否介导了亚硝酸盐的影响。此外，我们还检测了偶氮氧甲烷（AOM）对饮用正常水和含亚硝酸盐水的小鼠肠道微生物群的影响。高亚硝酸盐对C57BL/6小鼠有毒性作用。同时，高亚硝酸盐诱导小鼠皮肤病变，血清ALT、结肠IL-6、TNF-α、MDA水平升高，血清Cr、结肠sIgA、T-AOC水平降低。将粪便菌群移植到正常小鼠体内后，亚硝酸盐调节的肠道菌群也可引起皮肤病变，并伴有血清Cr降低，结肠MDA升高。高剂量亚硝酸盐引起阿里斯特菌、普雷沃氏菌和鲁米诺球菌的上调，这些细菌可以通过FMT移植到正常小鼠体内。相反，正常小鼠的肠道微生物群降低了亚硝酸盐对血清ALT和Cr以及结肠sIgA和MDA的影响。正常小鼠的肠道菌群也可以上调亚硝酸盐处理小鼠的代谢基因，下调应激基因。这可能是由于由正常水处理小鼠到亚硝酸盐处理小鼠的FMT引起的akkermansians和副结核菌的上调。此外，与正常水处理小鼠相比，亚硝酸盐处理小鼠的AOM对结肠的毒性更大，这可能是由于hspa1和hspa1在结肠中的表达。有趣的是，与亚硝酸盐处理的小鼠相比，正常水处理小鼠的肠道微生物群受到AOM的影响更大。总之，这些数据表明，肠道菌群介导了高浓度亚硝酸盐的毒性。
Growing evidence indicates that exposure to high levels of nitrite for a prolonged time has adverse health effects. Although gut microbiota is responsible for the transformation of nitrite in the gut, the evidence concerning whether gut microbiota mediates the toxicity of nitrite is still lacking. The present study addressed the long-term effects of dietary nitrite on male C57BL/6 mice and employed fecal microbiota transplantation (FMT) to reveal whether gut microbiota mediated the effects of nitrite. Furthermore, the effect of azoxymethane (AOM) on gut microbiota was detected for mice drinking normal or nitrite-containing water. High nitrite had toxic effects on C57BL/6 mice. Meanwhile, high nitrite induced skin lesions in mice, accompanied with increased serum ALT, colon IL-6, TNF-α, and MDA levels, together with decreased serum Cr, colon sIgA, and T-AOC levels. After fecal microbiota was transplanted into the normal mice, the nitrite-regulated gut microbiota could also induce skin lesions, coupled with reduced serum Cr, and increased colon MDA. The high dose of nitrite caused the upregulations ofAlistipes,Prevotella,andRuminococcus, which could be transplanted into normal mice through FMT. Inversely, gut microbiota from normal mice reduced the effects of nitrite on serum ALT and Cr, together with colon sIgA and MDA. Gut microbiota from normal mice could also upregulate metabolic genes and downregulate stress genes in the nitrite-treated mice. It might due to the upregulation ofAkkermansiaandParabacteroidescaused by FMT from normal water-treated mice to nitrite-treated mice. In addition, AOM exhibited to be more toxic to the colon in the nitrite-treated mice in comparison with normal water-treated mice, and it might be due to the expression ofHspa1aandHspa1bin the colon. Interestingly, gut microbiota was more influenced by AOM in the normal water-treated mice than the nitrite-treated mice. Overall, these data demonstrated that gut microbiota mediated the toxicity of a high concentration of dietary nitrite.