Are Fecal Metabolome and Microbiota Profiles Correlated with Autism Severity? A Cross-Sectional Study on ASD Preschoolers.

Luca Laghi,Margherita Prosperi,Maria Aurora Morales,Letizia Guiducci,Paola Mastromarino,Elisa Santocchi,Sara Calderoni,Filippo Muratori

doi:10.3390/metabo11100654

Abstract

Autism spectrum disorders (ASD) make up a heterogeneous group of neurodevelopmental disorders characterized by social and communication difficulties associated with repetitive and restrictive behaviors. Besides core features, metabolic imbalances, inflammation, gastrointestinal (GI) symptoms, and altered gut microbiota composition were often described in association with ASD, but their connection with the severity of autism (SA) remains unexplored. In this study, fecal metabolome, microbiota, and calprotectin levels of 80 ASD preschoolers were quantified and correlated with SA. Twelve of the fifty-nine molecules that were quantified by fecal metabolome analysis were significantly associated with SA. No links between SA or GI symptoms and microorganisms’ relative abundance were highlighted. Significant correlations between bifidobacteria, Sutterella, lactobacilli relative abundance, and metabolomics profiles were found. These results suggest that fecal metabolome discriminates the SA and intestinal microorganisms mediate the link between metabolome and SA regardless of GI symptomatology. The study raises the possibility that grouping ASD populations through metabolomics and fecal microbiota could aid the identification of specific ASD endophenotypes, on the basis of the SA. Mechanistic studies focusing on detected biomarkers might be an option for future studies.

Highlights

Autism spectrum disorders (ASD) are a clinically and genetically heterogeneous group of neurodevelopmental disorders characterized by socio-communicative difficulties as well as repetitive and restrictive behaviors [1]
To evaluate the metabolome’s features potentially related to autism independently from the presence of gastrointestinal symptoms, we focused on children classified as low-autism diagnostic observation schedule (ADOS) and high-ADOS, and we applied a two-way ANOVA on each molecule
This study aims to identify whether water-soluble fecal metabolome, microbiota, and calprotectin levels correlate with severity of autism (SA) levels in a group of ASD preschoolers

Summary

Introduction

Autism spectrum disorders (ASD) are a clinically and genetically heterogeneous group of neurodevelopmental disorders characterized by socio-communicative difficulties as well as repetitive and restrictive behaviors [1]. Goodwin et al [2] and subsequently other authors [3,4,5,6] noticed that a large proportion of ASD subjects has gastrointestinal (GI) dysfunctions, with diarrhea, constipation, and abdominal pain reported as the most common symptoms [7]. The underlying multifaceted mechanisms connecting ASD and GI problems have still not been completely elucidated, but several studies have focused on the gut microbiota as a potential link between ASD and GI symptoms. Some microbiota perturbations have been consistently found in ASD subjects, suggesting the possible role of the gut microbiota as a contributing factor in the etiopathogenesis of ASD [8]. Several studies suggested that decreases of Bifidobacterium spp. and increases of Bacteroides spp. in stool samples characterize the microbiota of ASD individuals [9]. Variations of different clostridial clusters, Sutterella and Akkermansia genera gave contradictory results across studies

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