Multivariate Analysis of Fecal Metabolites from Children with Autism Spectrum Disorder and Gastrointestinal Symptoms before and after Microbiota Transfer Therapy

Fatir Qureshi,Kathryn Hanagan,Rosa Krajmalnik-Brown,James Adams,Juergen Hahn,Dae-Wook Kang

doi:10.3390/jpm10040152

Abstract

Fecal microbiota transplant (FMT) holds significant promise for patients with Autism Spectrum Disorder (ASD) and gastrointestinal (GI) symptoms. Prior work has demonstrated that plasma metabolite profiles of children with ASD become more similar to those of their typically developing (TD) peers following this treatment. This work measures the concentration of 669 biochemical compounds in feces of a cohort of 18 ASD and 20 TD children using ultrahigh performance liquid chromatography-tandem mass spectroscopy. Subsequent measurements were taken from the ASD cohort over the course of 10-week Microbiota Transfer Therapy (MTT) and 8 weeks after completion of this treatment. Univariate and multivariate statistical analysis techniques were used to characterize differences in metabolites before, during, and after treatment. Using Fisher Discriminant Analysis (FDA), it was possible to attain multivariate metabolite models capable of achieving a sensitivity of 94% and a specificity of 95% after cross-validation. Observations made following MTT indicate that the fecal metabolite profiles become more like those of the TD cohort. There was an 82–88% decrease in the median difference of the ASD and TD group for the panel metabolites, and among the top fifty most discriminating individual metabolites, 96% report more comparable values following treatment. Thus, these findings are similar, although less pronounced, as those determined using plasma metabolites.

Highlights

Autism spectrum disorder (ASD) encompasses a large group of early onset neurological conditions that result in impairments in social behavior and communication, which are estimated to affect 1 in 54 children under the age of eight in the United States [1]
In order to classify Autism Spectrum Disorder (ASD) and typically developing (TD) cohorts at their Week 0 measurements, the area under the AUROC was used as an assessment of the potential of a metabolite to distinguish between ASD and TD groups
This study investigated differences in fecal metabolites between a group of children diagnosed with ASD and GI symptoms and their typically developing peers with no history of GI symptoms

Summary

Introduction

Autism spectrum disorder (ASD) encompasses a large group of early onset neurological conditions that result in impairments in social behavior and communication, which are estimated to affect 1 in 54 children under the age of eight in the United States [1] Despite this high rate of occurrence, the understanding of the pathophysiology of ASD is still poor, and it is believed that at least in some cases ASD begins prenatally as a result of complex interactions between environmental and genetic factors [2,3]. The microbiota of individuals with ASD without the presence of GI issues have consistently been found to be distinct from their typically developing (TD) peers [10,11] Certain genera such as Prevotella and Coprococcus have been shown to be significantly less prevalent in the gut of children with ASD [12,13]. It has been proposed that the microbiota differences in children with ASD give rise to metabolomic differences that can be quantitatively evaluated to distinguish them from their TD peers [14,15]

Objectives

Methods

Results

Discussion

Conclusion