Integrated 16S rRNA Sequencing, Metagenomics, and Metabolomics to Characterize Gut Microbial Composition, Function, and Fecal Metabolic Phenotype in Non-obese Type 2 Diabetic Goto-Kakizaki Rats
Integrated 16S rRNA Sequencing, Metagenomics, and Metabolomics to Characterize Gut Microbial Composition, Function, and Fecal Metabolic Phenotype in Non-obese Type 2 Diabetic Goto-Kakizaki Rats
复制标题
综合 16S rRNA 测序、宏基因组学和代谢组学来表征非肥胖 2 型糖尿病 Goto-Kakizaki 大鼠的肠道微生物组成、功能和粪便代谢表型
DOI：
10.3389/fmicb.2019.03141
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发表时间：
2020-01-20
影响因子：
5.2
通讯作者：
Qin, Yu-hui
中科院分区：
文献类型：
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作者：
Peng, Weijun;Huang, Jianhua;Qin, Yu-hui
2型糖尿病（T2DM）是世界上最常见的内分泌疾病之一。最近的研究表明，肠道菌群失调可能是T2DM发病的重要因素。然而，肠道微生物组和粪便代谢组在T2DM中作用的机制尚未明确。最近，为了研究人类T2DM的临床症状和特征，建立了Goto-Kakizaki （GK）大鼠T2DM模型。为了进一步研究T2DM发病机制，我们结合多组学技术，包括16S rRNA基因测序、宏基因组测序和代谢组学，分析了GK大鼠的肠道微生物组成和功能，并进一步表征了粪便代谢组学特征。我们的研究结果显示，GK大鼠的肠道微生物组成显著改变，这可以通过微生物多样性减少、微生物分类群分布改变和肠道微生物组相互作用网络的改变来证明。基于同源群簇（COG）和京都基因与基因组百科全书（KEGG）注释的功能分析表明，GK大鼠有5个功能COG类属于代谢簇，有33个与代谢相关的KEGG通路显著富集。代谢组学分析在GK大鼠中发现了53种显著差异丰富的代谢物，包括脂质和类脂分子。这些脂质在甘油磷脂代谢途径中富集。此外，功能相关分析显示，一些改变的肠道微生物群家族，如Verrucomicrobiaceae和Bacteroidaceae，与粪便代谢物的改变显著相关。总的来说，结果表明肠道微生物群的改变与T2DM的发病机制有关。
Type 2 diabetes mellitus (T2DM) is one of the most prevalent endocrine diseases in the world. Recent studies have shown that dysbiosis of the gut microbiota may be an important contributor to T2DM pathogenesis. However, the mechanisms underlying the roles of the gut microbiome and fecal metabolome in T2DM have not been characterized. Recently, the Goto-Kakizaki (GK) rat model of T2DM was developed to study the clinical symptoms and characteristics of human T2DM. To further characterize T2DM pathogenesis, we combined multi-omics techniques, including 16S rRNA gene sequencing, metagenomic sequencing, and metabolomics, to analyze gut microbial compositions and functions, and further characterize fecal metabolomic profiles in GK rats. Our results showed that gut microbial compositions were significantly altered in GK rats, as evidenced by reduced microbial diversity, altered microbial taxa distribution, and alterations in the interaction network of the gut microbiome. Functional analysis based on the cluster of orthologous groups (COG) and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotations suggested that 5 functional COG categories belonged to the metabolism cluster and 33 KEGG pathways related to metabolic pathways were significantly enriched in GK rats. Metabolomics profiling identified 53 significantly differentially abundant metabolites in GK rats, including lipids and lipid-like molecules. These lipids were enriched in the glycerophospholipid metabolic pathway. Moreover, functional correlation analysis showed that some altered gut microbiota families, such as Verrucomicrobiaceae and Bacteroidaceae, significantly correlated with alterations in fecal metabolites. Collectively, the results suggested that an altered gut microbiota is associated with T2DM pathogenesis.