Abstract
Autism spectrum disorder (ASD) is a complex neurological and developmental disorder, and a growing body of literature suggests the presence of autonomic nervous system (ANS) dysfunction in individuals with ASD. ANS is part of the “gut brain axis”, which consists of an intricate interplay between the gut microbiome, mucosal immune system, enteric nervous system, ANS, and central processes receiving input from the vagus nerve. Measurements of the gut microbiome and the autonomic indices can serve as non-invasive markers of the status of the gut-brain axis in ASD. To our knowledge, no previous studies have explored the relationship between ANS and gut microbiome in individuals with ASD. Furthermore, while previous studies investigated the use of autonomic indices and gut microbiome independently as markers of ASD-related comorbidities, such as anxiety, cardiovascular issues, and gastrointestinal dysfunction, the use of combined autonomic indices and gut microbiome factors to classify ASD and control subjects has not been explored. In this study, we characterized autonomic function of a group of individuals with ASD in comparison to their paired, first-degree relative controls. Second, we explored the ASD gut-brain-axis through the relationship between gut microbiome markers and autonomic indices, as well as the correlation between the gut-brain-axis and clinical presentation of ASD. Lastly, this study explores the predictive capability of gut-brain-axis biomarkers (including autonomic and microbiome indices) in subtyping ASD cases, serving as a starting point to investigate the possibility of assisting in ASD screening and diagnosis that still heavily relies on psychological testing, which may be based on highly subjective standards.
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Data Availability
All the data and code scripts in this project have been deposited to https://doi.org/10.6084/m9.figshare.11369133.v1.
Abbreviations
- AD(H)D:
-
Attention deficit (hyperactivity) disorder
- ANS:
-
Autonomic nervous system
- ASD:
-
Autism spectrum disorders
- ATEC:
-
Autism treatment evaluation checklist
- AUC:
-
Area under the curve
- BVP:
-
Blood volume pulse
- CI:
-
Confidence interval
- CNS:
-
Central nervous system
- cvNNI:
-
Coefficient of variation
- CVSD:
-
Coefficient of variation of successive differences
- DSM-5:
-
Diagnostic and statistical manual of mental disorders
- EDA:
-
Electrodermal activity
- FDR:
-
False discovery rate
- GI:
-
Gastrointestinal
- HR:
-
Heart rate
- IBI:
-
Interbeat interval
- IQ:
-
Intelligence quotient
- LOOCV:
-
Leave-one-out cross-validation
- MGH:
-
Massachusetts general hospital
- NNI50:
-
Number of pairs of successive NN (R–R) intervals that differ by more than 50 ms
- OASIS:
-
Overall anxiety severity impairment scale
- PCA:
-
Principal component analysis
- PHQ-9:
-
Patient health questionnaire
- pNNI50:
-
Percentage of adjacent NN (R–R) intervals that differ by more than 50 ms
- RMSSD:
-
Root mean square of successive differences
- ROC:
-
Receiver operator characteristics
- rRNA:
-
Ribosomal RNA
- sdNN:
-
Standard deviation of NN (R–R) intervals
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Acknowledgments
Dr. Hang Lee, Harvard Catalyst biostatistics core. Dr. Yiqing Song, University of Indiana. Dr. Cunjian Dong, Massachusetts General Hospital.
Funding
This study was funded by Massachusetts General Hospital Grant Number 230361 at the Athinoula A. Martinos Center for Biomedical Imaging, Boston, MA.
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XK devised the project and the main conceptual ideas. XK, MK and JL worked out almost all of the technical details, and XK, JL and MK performed data collections and measurements with help from KL and CH. JL, KL, RT and CH performed bioinformatics analyses and statistical analyses, with assistance from MZ and QC and input from HL; XK and JL wrote the manuscript, with assistance from KL, RT, and MF, and input from JK; JL, KL, and RT drafted the figures with input from XK and JK; XK, JK, JL, KL, RT, and MF participated in manuscript editing.
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Kong, X., Liu, J., Liu, K. et al. Altered Autonomic Functions and Gut Microbiome in Individuals with Autism Spectrum Disorder (ASD): Implications for Assisting ASD Screening and Diagnosis. J Autism Dev Disord 51, 144–157 (2021). https://doi.org/10.1007/s10803-020-04524-1
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DOI: https://doi.org/10.1007/s10803-020-04524-1