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蒙古族肥胖儿童肠道菌群及代谢的多组学研究

Multiomics Study on Intestinal Flora and Metabolism of Mongolian Obese Children

  • 摘要: 本文旨在探讨蒙古族肥胖儿童肠道菌群及其代谢物间的联系。选择内蒙古自治区通辽市蒙古族肥胖儿童15名作为肥胖组,正常体重儿童15名作为正常组。收集两组儿童粪便样本,用16S rDNA技术检测肠道微生物,分析两组粪便肠道菌群的多样性及差异性,采用气相色谱-质谱(gaschromatography-mass spectrometry, GC-MS)技术,筛选两组粪便差异代谢物,并进行富集分析通路预测。结果显示,肥胖组儿童粪便中拟杆菌门(Bacteroidetes)和厚壁菌门(Firmicutes)丰度均低于正常组的(P<0.05),放线菌门(Actinobacteria)和变形菌门(Proteobacteria)丰度均高于正常组的(P<0.05);肥胖组与正常组间有7种共有优势菌属存在显著差异(P<0.05),其中4种菌属在肥胖组中下调,3种菌属在肥胖组中上调;两组间有12种代谢物存在差异(P<0.05),肥胖组中酪氨酸、四氢皮质酮等6种代谢物含量减少,核糖酸内酯、 4-胆甾烯-3-酮等6种代谢物的含量增加;对差异代谢物富集分析后发现代谢途径的改变集中在苯丙氨酸、酪氨酸和色氨酸生物合成等方面;将差异菌属和差异代谢物进行相关性分析,发现另枝菌属(Alistipes)与4-胆甾烯-3-酮呈负相关;拟杆菌属(Bacteroides)、瘤胃球菌属(Ruminococcus)、另枝菌属与瓜氨酸,布劳氏菌属(Blautia)与N-乙酰-D-甘露糖胺、核糖酸内酯,假丁酸弧菌属(Pseudobutyrivibrio)与4-胆甾烯-3-酮均呈正相关。蒙古族正常体重和肥胖儿童肠道菌群的结构与粪便代谢谱均存在差异,且二者存在相关性。瓜氨酸、 4-胆甾烯-3-酮、核糖酸内酯和N-乙酰-D-甘露糖胺是蒙古族儿童肥胖发生发展的潜在生物标记物。

     

    Abstract: This study aims to explore the relationship between intestinal flora and its metabolites of Mongolian obese children. 15 Mongolian obese children were selected as obesity group and 15 Mongolian normal weight children were selected as normal group in Tongliao city of the Inner Mongolia Autonomous Region. The fecal samples of two groups of children were collected, the intestinal microbes were detected by 16S rDNA technique, and the diversity and difference of intestinal flora between the two groups of feces were analyzed. The differential metabolites between the two groups of feces were screened by gaschromatography-mass spectrometry(GC-MS) technology, and the enrichment analysis pathway was predicted. Results showed the abundance of Bacteroides and Firmicutes in feces of obesity group children was lower than that of normal group children(P<0.05), while the abundance of Actinobacteria and Proteobacteria of obesity group were higher than that of normal group(P<0.05). There were significant differences between obesity group and normal group in 7 common dominant genera(P<0.05), among which 4 genera were down-regulated and 3 genera were up-regulated in obesity group. Here were differences among 12 metabolites(P<0.05), the contents of 6 metabolites such as tyrosine and tetrahydrocorticosterone decreased, while the contents of 6 metabolites such as ribolactone and 4-Cholesten-3-one increased. After the analysis of differential metabolites enrichment, it was found that the changes of metabolic pathways mainly focused on the phenylalanine, tyrosine and tryptophan biosynthesis. According to the correlation analysis between different bacteria and different metabolites, Alistipes was negatively correlated with 4-Cholesten-3-one, Bacteroides, Ruminococcus and Alistipes with citrulline, Blautia with N-Acetyl-D-mannosamine and ribonolactone, and Pseudobutyrivibrio with 4-Cholesten-3-one were positively correlated. There are differences in the structure of intestinal flora and fecal metabolic spectrum between normal group and obesity group, and there is a correlation between the two. Citrulline, 4-Cholesten-3-one, N-Acetyl-D-mannosamine and ribonolactone and may become biomarkers of obesity in Mongolian children.

     

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