Alterations in intestinal microbiota and metabolites in individuals with Down syndrome and their correlation with inflammation and behavior disorders in mice

文献类型： 外文期刊

第一作者： Cai, Shaoli

作者： Cai, Shaoli;Lin, Jinxin;Liu, Songnian;Feng, Zhihua;Zhang, Yangfan;Chen, Qi;Cai, Shaoli;Lin, Jinxin;Liu, Songnian;Feng, Zhihua;Zhang, Yangfan;Chen, Qi;Cai, Shaoli;Lin, Jinxin;Feng, Zhihua;Zhang, Yangfan;Zhang, Yanding;Huang, Jianzhong;Chen, Qi;Li, Zhaolong

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关键词： Down syndrome; cytokines; intestinal microbiota; metabolomics; inflammation

期刊名称：FRONTIERS IN MICROBIOLOGY （ 影响因子：5.2； 五年影响因子：6.2 ）

ISSN：

年卷期： 2023 年 14 卷

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收录情况： SCI

摘要： The intestinal microbiota and fecal metabolome have been shown to play a vital role in human health, and can be affected by genetic and environmental factors. We found that individuals with Down syndrome (DS) had abnormal serum cytokine levels indicative of a pro-inflammatory environment. We investigated whether these individuals also had alterations in the intestinal microbiome. High-throughput sequencing of bacterial 16S rRNA gene in fecal samples from 17 individuals with DS and 23 non-DS volunteers revealed a significantly higher abundance of Prevotella, Escherichia/Shigella, Catenibacterium, and Allisonella in individuals with DS, which was positively associated with the levels of pro-inflammatory cytokines. GC-TOF-MS-based fecal metabolomics identified 35 biomarkers (21 up-regulated metabolites and 14 down-regulated metabolites) that were altered in the microbiome of individuals with DS. Metabolic pathway enrichment analyses of these biomarkers showed a characteristic pattern in DS that included changes in valine, leucine, and isoleucine biosynthesis and degradation; synthesis and degradation of ketone bodies; glyoxylate and dicarboxylate metabolism; tyrosine metabolism; lysine degradation; and the citrate cycle. Treatment of mice with fecal bacteria from individuals with DS or Prevotella copri significantly altered behaviors often seen in individuals with DS, such as depression-associated behavior and impairment of motor function. These studies suggest that changes in intestinal microbiota and the fecal metabolome are correlated with chronic inflammation and behavior disorders associated with DS.

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