肠道菌群参与黑木耳黑色素改善小鼠缺铁性贫血的代谢组学研究

Metabonomic Study of the Involvement of the Intestinal Microflora in the Improvement of Iron Deficiency Anemia(IDA)by Auricularia auricula Melanin in Mice

缺铁性贫血(iron deficiency anemia,IDA)是常见铁营养缺乏性疾病,已成为世界范围内的主要公共卫生问题之一。前期研究表明黑木耳黑色素具有改善IDA的作用,然而其具体作用机制不明。本实验采用抗生素鸡尾酒的菌群剔除方法及代谢组学技术,研究肠道菌群在黑色素改善IDA中的作用。结果表明黑木耳黑色素干预能显著改善IDA小鼠体质量及血红蛋白质量浓度、红细胞压积、平均红细胞体积和血小板数目等贫血指标,剔除肠道菌群,黑木耳黑色素失去改善IDA的作用。代谢组学研究鉴定出76个差异代谢物,通路富集分析筛选到色氨酸代谢,苯丙氨酸、酪氨酸和色氨酸生物合成,抗坏血酸和醛酸代谢,谷胱甘肽代谢,酪氨酸代谢,戊糖和葡萄糖醛酸的相互转化和类固醇激素生物合成7条通路,其中色氨酸代谢最为显著。在肠道菌群的参与下,补充黑木耳黑色素的IDA小鼠体内色氨酸代谢产物5-羟基吲哚乙酸、N-甲酰犬尿氨酸显著积累,表明黑木耳黑色素可能通过肠道菌群激活色氨酸代谢发挥改善IDA的作用,本实验结果可为进一步研究黑木耳黑色素改善IDA的作用机制及产品开发提供理论依据。

Iron deficiency anemia(IDA)is a common iron deficiency disease.IDA has become one of the major public health problems worldwide.Our previous studies have shown that Auricularia auricula melanin(AAM)can alleviate IDA,but the mechanism is not clear.In this study,the role of the intestinal microflora in the improvement of IDA by AAM was studied by elimination of gut bacteria using an antibiotic cocktail as well as using metabonomics.The results showed that AAM treatment significantly alleviated anemia symptoms of IDA mice in terms of body mass,hemoglobin concentration,hematocrit,mean erythrocyte volume and platelet count,and this effect was lost when the intestinal flora was eliminated.Totally 76 differential metabolites were identified by metabolnomics analysis.Pathway enrichment analysis identified seven pathways including tryptophan metabolism,phenylalanine,tyrosine and tryptophan biosynthesis,ascorbic and uronic metabolism,glutathione metabolism,tyrosine metabolism,pentose and glucuronate interconversion and steroid hormone biosynthesis.Among these,tryptophan metabolism was most significant.In the presence of intestinal microflora,tryptophan metabolites such as 5-hydroxyindole acetic acid and N-formyl kynurenine were significantly accumulated in IDA mice supplemented with AAM,indicating that AAM could mitigate IDA,which may be related to activation of tryptophan metabolism through the intestinal flora.This study may provides a theoretical basis for further research on the mechanisms by which AAM improves IDA and for the development of anti-IDA products.