Analysis of gut microbiota profiles and microbe-disease associations in children with autism spectrum disorders in China

Mengxiang Zhang,Juan Wang,Juan Zhang,Wei Ma,Yi He

doi:10.1038/s41598-018-32219-2

Abstract

Autism spectrum disorder (ASD) is a set of complex neurodevelopmental disorders. Recent studies reported that children with ASD have altered gut microbiota profiles compared with typical development (TD) children. However, few studies on gut bacteria of children with ASD have been conducted in China. Here, in order to elucidate changes of fecal microbiota in children with ASD, 16S rRNA sequencing was conducted and the 16S rRNA (V3-V4) gene tags were amplified. We investigated differences in fecal microbiota between 35 children with ASD and 6 TD children. At the phylum level, the fecal microbiota of ASD group indicated a significant increase of the Bacteroidetes/Firmicutes ratio. At the genus level, we found that the relative abundance of Sutterella, Odoribacter and Butyricimonas was much more abundant in the ASD group whereas the abundance of Veillonella and Streptococcus was decreased significantly compared to the control group. Functional analysis demonstrated that butyrate and lactate producers were less abundant in the ASD group. In addition, we downloaded the association data set of microbe–disease from human microbe–disease association database and constructed a human disease network including ASD using our gut microbiome results. In this microbe–disease network based on microbe similarity of diseases, we found that ASD is positively correlated with periodontal, negatively related to type 1 diabetes. Therefore, these results suggest that microbe-based disease analysis is able to predict novel connection between ASD and other diseases and may play a role in revealing the pathogenesis of ASD.

Highlights

Autism spectrum disorder (ASD) refers to a group of complex neurodevelopmental disorders with early life stage, characterized by deficits in social communication and by restricted and fixated behavior
Most studies of the gut microbiota in patients with ASD have been focused on Western populations, it is important to expand these studies to non-Western diet populations in order to fully understand the range of variation of the gut microbiota in patients with ASD and how gut microbes affect the pathogenesis of ASD
We investigated 254 KEGG pathways.The result of KEGG pathways analysis showed that D− Arginine and D−ornithine metabolism, ether lipid metabolism, bacterial chemotaxis, neurodegenerative diseases -prion diseases, phosphotransferase system (PTS) and flagellar assembly genes were more abundant in ASD group than that of control group while meiosis-yeast, steroid hormone biosynthesis, glycosaminoglycan degradation and lipoic acid metabolism were enriched in the control group (p value < 0.05, Wilcoxon rank-sum test, Fig. 4b, Supporting Dataset S2)

Summary

Introduction

Autism spectrum disorder (ASD) refers to a group of complex neurodevelopmental disorders with early life stage, characterized by deficits in social communication and by restricted and fixated behavior. Our study discovered the difference in the fecal microbiota between ASD and control groups. At the level of phylum, the ratio of Bacteroidetes/Firmicutes (p < 0.05, Wilcoxon rank-sum test; Fig. 1a.) was significantly higher in the ASD group compared to the control group due to a significant increase of the relative abundance of Bacteroidetes (FDR-corrected p < 0.05, Wilcoxon rank-sum test; Fig. 1b).

Results

Conclusion