skip to main content

Title: Longitudinal study of stool-associated microbial taxa in sibling pairs with and without autism spectrum disorder

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder influenced by both genetic and environmental factors. Recently, gut dysbiosis has emerged as a powerful contributor to ASD symptoms. In this study, we recruited over 100 age-matched sibling pairs (between 2 and 8 years old) where one had an Autism ASD diagnosis and the other was developing typically (TD) (432 samples total). We collected stool samples over four weeks, tracked over 100 lifestyle and dietary variables, and surveyed behavior measures related to ASD symptoms. We identified 117 amplicon sequencing variants (ASVs) that were significantly different in abundance between sibling pairs across all three timepoints, 11 of which were supported by at least two contrast methods. We additionally identified dietary and lifestyle variables that differ significantly between cohorts, and further linked those variables to the ASVs they statistically relate to. Overall, dietary and lifestyle features were explanatory of ASD phenotype using logistic regression, however, global compositional microbiome features were not. Leveraging our longitudinal behavior questionnaires, we additionally identified 11 ASVs associated with changes in reported anxiety over time within and across all individuals. Lastly, we find that overall microbiome composition (beta-diversity) is associated with specific ASD-related behavioral characteristics.

; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ;
Publication Date:
Journal Name:
ISME Communications
Nature Publishing Group
Sponsoring Org:
National Science Foundation
More Like this
  1. Abstract

    Atypical neural responses to language have been found in toddlers with autism spectrum disorder (ASD) and in their unaffected siblings. However, given that language difficulties are often seen in these children, it is difficult to interpret whether these neural differences are a result of the diagnosis ofASDor impairments in their language abilities. In this study, we recorded event‐related potentials (ERPs) from four groups of 36‐month‐olds: low‐risk control (LRC), high risk forASDdefined as having an older sibling withASD(HRA) but who do not haveASDor milder autism‐like symptoms (HRA‐Typ),HRAchildren who do not haveASDbut exhibit milder autism‐like symptoms (HRA‐Atyp) andHRAchildren diagnosed withASD(ASD). Children listened to words expected to be acquired early (e.g. ball) and words expected to be acquired late (e.g. calf).ERPs were analysed over time windows sensitive to word processing as well as frontal and temporo‐parietal sites over the left and right hemispheres. When controlling for language abilities, there were group differences within the temporo‐parietal sites. Specifically, theHRA‐Atyp group showed a different timed response to late words compared to theASDandLRCgroups. In addition, we found a relation between neural responses in the left frontalmore »sites andASDseverity. Our results suggest that both language abilities andASDdiagnoses are important to consider when interpreting neural differences in lexical processing.

    « less
  2. Lay Summary

    This study tested the use of a tablet in the behavioral assessment of young children with autism. Children watched a series of developmentally appropriate movies and their facial expressions were recorded using the camera embedded in the tablet. Results suggest that computational assessments of facial expressions may be useful in early detection of symptoms of autism.

    « less
  3. Lay Summary

    Previous research has identified atypicalities in prosody (e.g., intonation) in individuals with ASD and a subset of their first‐degree relatives. In order to better understand the mechanisms underlying prosodic differences in ASD, this study examined how individuals with ASD and their parents responded to unexpected differences in what they heard themselves say to modify control of their voice (i.e., audio‐vocal integration). Results suggest that disruptions to audio‐vocal integration in individuals with ASD contribute to ASD‐related prosodic atypicalities, and the more subtle differences observed in parents could reflect underlying genetic liability to ASD.

    « less
  4. Abstract Background

    Repetitive action, resistance to environmental change and fine motor disruptions are hallmarks of autism spectrum disorder (ASD) and other neurodevelopmental disorders, and vary considerably from individual to individual. In animal models, conventional behavioral phenotyping captures such fine-scale variations incompletely. Here we observed male and female C57BL/6J mice to methodically catalog adaptive movement over multiple days and examined two rodent models of developmental disorders against this dynamic baseline. We then investigated the behavioral consequences of a cerebellum-specific deletion in Tsc1 protein and a whole-brain knockout in Cntnap2 protein in mice. Both of these mutations are found in clinical conditions and have been associated with ASD.


    We used advances in computer vision and deep learning, namely a generalized form of high-dimensional statistical analysis, to develop a framework for characterizing mouse movement on multiple timescales using a single popular behavioral assay, the open-field test. The pipeline takes virtual markers from pose estimation to find behavior clusters and generate wavelet signatures of behavior classes. We measured spatial and temporal habituation to a new environment across minutes and days, different types of self-grooming, locomotion and gait.


    Both Cntnap2 knockouts and L7-Tsc1 mutants showed forelimb lag during gait. L7-Tsc1 mutants and Cntnap2 knockouts showed complexmore »defects in multi-day adaptation, lacking the tendency of wild-type mice to spend progressively more time in corners of the arena. In L7-Tsc1 mutant mice, failure to adapt took the form of maintained ambling, turning and locomotion, and an overall decrease in grooming. However, adaptation in these traits was similar between wild-type mice and Cntnap2 knockouts. L7-Tsc1 mutant and Cntnap2 knockout mouse models showed different patterns of behavioral state occupancy.


    Genetic risk factors for autism are numerous, and we tested only two. Our pipeline was only done under conditions of free behavior. Testing under task or social conditions would reveal more information about behavioral dynamics and variability.


    Our automated pipeline for deep phenotyping successfully captures model-specific deviations in adaptation and movement as well as differences in the detailed structure of behavioral dynamics. The reported deficits indicate that deep phenotyping constitutes a robust set of ASD symptoms that may be considered for implementation in clinical settings as quantitative diagnosis criteria.

    « less
  5. Abstract Olfaction supports a multitude of behaviors vital for social communication and interactions between conspecifics. Intact sensory processing is contingent upon proper circuit wiring. Disturbances in genetic factors controlling circuit assembly and synaptic wiring can lead to neurodevelopmental disorders, such as autism spectrum disorder (ASD), where impaired social interactions and communication are core symptoms. The variability in behavioral phenotype expression is also contingent upon the role environmental factors play in defining genetic expression. Considering the prevailing clinical diagnosis of ASD, research on therapeutic targets for autism is essential. Behavioral impairments may be identified along a range of increasingly complex social tasks. Hence, the assessment of social behavior and communication is progressing towards more ethologically relevant tasks. Garnering a more accurate understanding of social processing deficits in the sensory domain may greatly contribute to the development of therapeutic targets. With that framework, studies have found a viable link between social behaviors, circuit wiring, and altered neuronal coding related to the processing of salient social stimuli. Here, the relationship between social odor processing in rodents and humans is examined in the context of health and ASD, with special consideration for how genetic expression and neuronal connectivity may regulate behavioral phenotypes.