Virulence factor-related gut microbiota genes and immunoglobulin A levels as novel markers for machine learning-based classification of autism spectrum disorder

Mingbang Wang,Chunquan Cai,Zhaoqing Yin,Ceymi Doenyas,Yanqing Liu,Jiaxiu Zhou,Shujuan Zeng,Wenhao Zhou,Jing Wan

doi:10.1016/j.csbj.2020.12.012

Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental condition for which early identification and intervention is crucial for optimum prognosis. Our previous work showed gut Immunoglobulin A (IgA) to be significantly elevated in the gut lumen of children with ASD compared to typically developing (TD) children. Gut microbiota variations have been reported in ASD, yet not much is known about virulence factor-related gut microbiota (VFGM) genes. Upon determining the VFGM genes distinguishing ASD from TD, this study is the first to utilize VFGM genes and IgA levels for a machine learning-based classification of ASD. Sequence comparisons were performed of metagenome datasets from children with ASD (n=43) and TD children (n=31) against genes in the virulence factor database. VFGM gene composition was associated with ASD phenotype. VFGM gene diversity was higher in children with ASD and positively correlated with IgA content. As Group B streptococcus (GBS) genes account for the highest proportion of 24 different VFGMs between ASD and TD and positively correlate with gut IgA, GBS genes were used in combination with IgA and VFGMs diversity to distinguish ASD from TD. Given that VFGM diversity, increases in IgA, and ASD-enriched VFGM genes were independent of sex and gastrointestinal symptoms, a classification method utilizing them will not pertain only to a specific subgroup of ASD. By introducing the classification value of VFGM genes and considering that VFs can be isolated in pregnant women and newborns, these findings provide a novel machine learning-based early risk identification method for ASD.

Highlights

We found that three of nine Autism spectrum disorder (ASD)-enriched virulence factor-related gut microbiota (VFGM) genes, cpsH, cpsJ, and cpsO, were from Streptococcus agalactiae 2603 V/R, and the abundance of Streptococcus agalactiae 2603 V/R was increased in gut of ASD children with/without GI symptoms compared with that of typically developing (TD) children, (Fig. 3a), and the significant increase in gut Immunoglobulin A (IgA) levels in children with ASD was independent of the GI symptoms
Given that we have previously found GBS genes to account for the highest proportion of 24 different VFGMs, and that gut GBS gene abundance was positively correlated with gut IgA level, we further evaluated the correlation between Virulence factors (VFs) of GBS and ASD
We found that VFGM gene diversity was positively associated with IgA content, and that both VFGM gene diversity and IgA content were higher in children with ASD than in TD children

Summary

Introduction

Autism spectrum disorder (ASD) is a neurodevelopmental condition that affects 1 in 54 (1.9%) of 8-year-old children in the US [1], and 0.29% of 6 to 12-year-old children in China [2]. Virulence factors (VFs) are molecules produced by bacteria, viruses, fungi, and protozoa that enable a microorganism to establish itself on or within a host of a particular species and enhance its potential to cause disease [7]

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