孤独症谱系障碍儿童肠道菌群多样性研究及功能预测分析

Diversity and functional prediction of gut microbiota in children with autism spectrum disorder

摘要:

目的 分析孤独症谱系障碍（autism spectrum disorder，ASD）儿童肠道菌群结构和多样性，并预测分析菌群的代谢功能。 方法 采集30例ASD儿童（ASD组）和20例正常发育（typically developing，TD）儿童（TD组）的粪便样本。提取基因组DNA，PCR扩增16S rDNA V4区，使用Illumina NovaSeq6000平台进行高通量测序。分析2组肠道菌群的构成和分布特征，并预测分析菌群的代谢功能。 结果 ASD组和TD组儿童肠道菌群的α多样性指数（Chao1、Shannon和Simpson）比较差异均无统计学意义（P>0.05）。在门和纲水平，2组儿童肠道菌群的结构差异无统计学意义（P>0.05）。在属水平，ASD组巨单胞菌属、巴恩斯氏菌属、小杆菌属、巨球菌属、瘤胃球菌属扭链群及梭杆菌属的丰度大于TD组（P<0.05）。功能预测分析显示，ASD组肠道菌群的色氨酸降解、谷氨酸降解及丁酸盐生成等代谢功能的丰度低于TD组（P<0.05），而γ-氨基丁酸降解功能的丰度高于TD组（P<0.05）。 结论 ASD儿童和TD儿童肠道菌群的α多样性无显著差异，但属水平物种构成不同，菌群的代谢功能有差别。

Abstract:

Objective To study the structure and diversity of gut microbiota in children with autism spectrum disorder (ASD), and to predict the metabolic function of gut microbiota. Methods Fecal samples were collected from 30 ASD children (ASD group) and 20 typically developing (TD) children (TD group). Genomic DNA was extracted, the 16S rDNA V4 region was amplified by PCR, and Illumina NovaSeq6000 platform was used for high-throughput sequencing. The composition and distribution characteristics of gut microbiota were analyzed for the two groups, and the metabolic function of gut microbiota was predicted. Results There were no significant differences in alpha diversity indices (Chao1, Shannon, and Simpson) of gut microbiota between the ASD and TD groups (P>0.05). At the phylum and class levels, there was no significant difference in the structure of gut microbiota between the two groups (P>0.05). Compared with the TD group, the ASD group had significantly higher abundance of Megamonas, Barnesiella, Dialister, Megasphaera, Ruminococcus_torques_group, and Fusobacterium at the genus level (P<0.05). Functional prediction analysis showed that compared with the TD group, the ASD group had a significantly lower abundance of the gut microbiota with the metabolic functions such as tryptophan degradation, glutamate degradation, and butyrate production (P<0.05) and a significantly higher abundance of the gut microbiota with the metabolic function of GABA degradation (P<0.05). Conclusions There is no significant difference in the alpha diversity of gut microbiota between ASD children and TD children, while there are differences in the composition of species at the genus level and the metabolic functions of gut microbiota.