Abstract
The hypothesized link between gut bacteria and autism spectrum disorder (ASD) has been explored through animal models and human studies with microbiome assessment after ASD presentation. We aimed to prospectively characterize the association between the infant/toddler gut microbiome and ASD-related social behaviors at age 3 years. As part of an ongoing birth cohort gut bacterial diversity, structure, taxa, and function at 6 weeks (n = 166), 1 year (n = 158), 2 years (n = 129), and 3 years (n = 140) were quantified with 16S rRNA gene and shotgun metagenomic sequencing (n = 101 six weeks, n = 103 one year). ASD-related social behavior was assessed at age 3 years using Social Responsiveness Scale (SRS-2) T-scores. Covariate-adjusted linear and permutation-based models were implemented. Microbiome structure at 1 year was associated with SRS-2 total T-scores (p = 0.01). Several taxa at 1, 2, and 3 years were associated with SRS-2 performance, including many in the Lachnospiraceae family. Higher relative abundance of Adlercreutzia equolifaciens and Ruminococcus torques at 1 year related to poorer SRS-2 performance. Two functional pathways, l-ornithine and vitamin B6 biosynthesis, were associated with better social skills at 3 years. Our results support potential associations between early-childhood gut microbiome and social behaviors. Future mechanistic studies are warranted to pinpoint sensitive targets for intervention.
Highlights
Autism spectrum disorder (ASD), a combination of disordered social behaviors and repetitive or restricted interests, affects one in 34 boys and one in 145 girls in the United States, with altered behaviors presenting in some children as early as 18 months of age or younger[1], but most children are not diagnosed until after age three[2,3,4,5,6,7,8]
A recent mechanistic study found that mice transfected with the stool of autism spectrum disorder (ASD) patients began displaying ASD behaviors, which were modified by a correction of the imbalance in bacterial metabolites brought on by transfection[25]
Our analysis uncovered the potential for several novel, time-dependent associations between the early-life gut microbiome and child social behaviors at age three
Summary
Autism spectrum disorder (ASD), a combination of disordered social behaviors and repetitive or restricted interests, affects one in 34 boys and one in 145 girls in the United States, with altered behaviors presenting in some children as early as 18 months of age or younger[1], but most children are not diagnosed until after age three[2,3,4,5,6,7,8]. Several case–control studies have compared the gut microbiome in children diagnosed with ASD to neurotypical siblings or community controls and observed notable differences[26,27,28,29,30,31,32,33]. These studies are subject to reverse causation, have been small, and have produced inconsistent results. No prospective cohort study has employed metagenomic sequencing and examined bacterial function in relation to social behaviors to better understand how gut bacteria may affect the brain. In addition to investigating bacterial diversity, structure, and specific taxa, we inferred gene function from metagenomic sequences to identify pathways associated with essential features of ASD
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