Multivariate Analysis of Plasma Metabolites in Children with Autism Spectrum Disorder and Gastrointestinal Symptoms Before and After Microbiota Transfer Therapy

James B Adams,Troy Vargason,Rosa Krajmalnik-Brown,Dae-Wook Kang,Juergen Hahn

doi:10.3390/pr7110806

James B Adams, Troy Vargason + Show 3 more

Open Access

https://doi.org/10.3390/pr7110806

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Abstract

Current diagnosis of autism spectrum disorder (ASD) is based on assessment of behavioral symptoms, although there is strong evidence that ASD affects multiple organ systems including the gastrointestinal (GI) tract. This study used Fisher discriminant analysis (FDA) to evaluate plasma metabolites from 18 children with ASD and chronic GI problems (ASD + GI cohort) and 20 typically developing (TD) children without GI problems (TD − GI cohort). Using three plasma metabolites that may represent three general groups of metabolic abnormalities, it was possible to distinguish the ASD + GI cohort from the TD − GI cohort with 94% sensitivity and 100% specificity after leave-one-out cross-validation. After the ASD + GI participants underwent Microbiota Transfer Therapy with significant improvement in GI and ASD-related symptoms, their metabolic profiles shifted significantly to become more similar to the TD − GI group, indicating potential utility of this combination of plasma metabolites as a biomarker for treatment efficacy. Two of the metabolites, sarcosine and inosine 5′-monophosphate, improved greatly after treatment. The third metabolite, tyramine O-sulfate, showed no change in median value, suggesting it and correlated metabolites to be a possible target for future therapies. Since it is unclear whether the observed differences are due to metabolic abnormalities associated with ASD or with GI symptoms (or contributions from both), future studies aiming to classify ASD should feature TD participants with GI symptoms and have larger sample sizes to improve confidence in the results.

Highlights

It is currently estimated that 1.7% of children in the United States are diagnosed with autism spectrum disorder (ASD) [1]
The objective of Fisher discriminant analysis (FDA) is to determine a linear combination of metabolites that best separates the ASD + GI and typically developing (TD) −
A discriminant score was calculated by FDA for each study participant by multiplying each input metabolite measurement by a calculated parameter value and summing these products together

Summary

Introduction

It is currently estimated that 1.7% of children in the United States are diagnosed with autism spectrum disorder (ASD) [1]. It is important to diagnose children with ASD as young as possible since available interventions are most effective if started early in life [5]. One national prevalence study of eight-year-olds with ASD found that the median age of diagnosis was 46 months for autism and 52 months for ASD [1]; this study did not account for children and adults diagnosed at ages above eight years, so the true median age of diagnosis is even higher. Stable diagnoses of ASD have been found in children as young as 18 months [6], representing a significant disconnect between current and ideal outcomes

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