Abstract

Environmental factors such as diet are known influencers on gastrointestinal (GI) microbiota variability and some diseases are associated with microbial stability. Whether microbial variability is related to symptoms of Autism Spectrum Disorder (ASD) and how diet impacts microbial stability in ASD is unknown. Herein, temporal variability in stool microbiota in relation to dietary habits in 2–7 years-old children with ASD (ASD, n = 26) and unaffected controls (CONT, n = 32) was investigated. Fecal samples were collected at baseline, 6-weeks and 6-months. Bacterial composition was assessed using 16S rRNA sequencing. Short fatty acid (SCFA) concentrations were analyzed by gas chromatography. Nutrient intake was assessed using a 3-day food diary and dietary patterns (DP) were empirically derived from a food frequency questionnaire. Social deficit scores (SOCDEF) were assessed using the Pervasive Developmental Disorder Behavior Inventory-Screening Version (PDDBI-SV). GI symptoms were assessed using the GI severity index. Overall, temporal variability in microbial structure, and membership did not differ between the groups. In children with ASD, abundances of Clostridiaceae, Streptophyta, and Clostridiaceae Clostridium, varied significantly, and concentrations of all SCFAs decreased over time. Variability in community membership was negatively correlated with median SOCDEF scores. Additionally, Clostridiales, Lactococcus, Turicibacter, Dorea, and Phascolarctobacterium were components of a more stable microbiota community in children with ASD. DP1, characterized by vegetables, starchy vegetables, legumes, nuts and seeds, fruit, grains, juice and dairy, was associated with changes in species diversity, abundance of Erysipelotricaceae, Clostridiaceae Clostridium, and Oscillospira and concentrations of propionate, butyrate, isobutyrate and isovalerate in children with ASD. DP2 characterized by fried, protein and starchy foods, “Kid's meals,” condiments, and snacks was associated with variations in microbiota structure, abundance of Clostridiaceae Clostridium, and Oscillospira and changes in all SCFA concentrations. However, no association between microbial stability and SOCDEF or GI severity scores were observed. In conclusion, microbiota composition varies over time in children with ASD, might be related to social deficit scores and can be impacted by diet. Future studies investigating the physiological effect of the changes in specific microbial taxa and metabolites are needed to delineate the impact on ASD symptomology.

Highlights

  • The gastrointestinal (GI) microbiota is increasingly being recognized for its ability to modulate host physiology, including host metabolism, immune function, as well as, behavior and cognition

  • In order to determine whether microbial stability was impacted by baseline dietary patterns, changes in microbiota abundance and short chain fatty acid (SCFA) concentrations in children with Autism Spectrum Disorder (ASD) were investigated based on dietary patterns

  • Increasing evidence supports microbial dysbiosis in children with ASD and some studies suggest that specific bacterial taxa might be associated with some symptoms of ASD [20, 21, 31]

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Summary

INTRODUCTION

The gastrointestinal (GI) microbiota is increasingly being recognized for its ability to modulate host physiology, including host metabolism, immune function, as well as, behavior and cognition. Understanding the long-term variability of the GI microbiota is important as resistance to environmental stressors and pathogen invasion, as well as, a rapid return to a baseline state after perturbation are key features of a healthy microbiome [5, 11]. In healthy children a dietary pattern that was characterized by higher intakes of vegetables and lower intakes of snacks, sweets and dairy food was associated with greater microbial stability over a 6-month period, demonstrating a direct relationship between dietary patterns and temporal variability of the fecal microbiota [19]. The goal of this longitudinal observational study was to test the hypothesis that children with ASD will have more variability in their microbiota compared to unaffected controls over a 6 month period and that a dietary pattern characterized by higher intakes of healthy foods such as fruits, vegetables and grains will be associated with a more stable microbiota composition. We further hypothesized that a higher degree of microbial variability over time will be associated with more severe ASD symptoms

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