Poster No:
338
Submission Type:
Abstract Submission
Authors:
Lisa Aziz-Zadeh1, Sofronia Ringold2, Skylar Tanartkit3, Aditya Jayashankar4, Emily Kilroy4, Christiana Butera4, Swapna Mahurkar-Joshi3, Mirella Dapretto3, Emeran Mayer3, Jennifer Labus3
Institutions:
1University of Southern California, BEVERLY HILLS, CA, 2University of Southern California, Los Angeles, CA, 3UCLA, Los Angeles, CA, 4USC, Los Angeles, CA
First Author:
Co-Author(s):
Introduction:
Prior studies have revealed significant associations between gut bacteria/metabolites and ASD symptomatology (Kang et al., 2018; Needham et al., 2021). However, to our knowledge, no human studies have directly examined associations between the gut microbiome and brain, which could in turn influence ASD behaviors. Here, we focus on stool-derived genera (e.g., Clostridium and Lactococcus) related to tryptophan metabolites, including serotonin, which have previously been associated with ASD (Gabriele et al., 2014). We link metagenomic data with task-related fMRI brain activity and behavioral data. fMRI tasks included those previously shown to elicit significant differences in ASD vs. typically developing (TD) controls, and relate to interoceptive processing (socio-emotional face processing tasks and disgust processing; Kilroy et al, 2021; Jayshakar et al 2024).
Methods:
Data Collection: 106 youth aged 8-18 [53 TD (M age=11.82 years, 30 males); 53 ASD (M age=12.05 years, 42 male)] provided a stool sample within 48 hours prior to completing fMRI. Parents/youth completed behavioral assessments related to early and present life factors. Participants completed two task runs in a 3T Siemens scanner: 1) viewing videos of emotional and non-emotional facial expressions; 2) viewing photos of disgusting foods and disgust facial expressions. Data Analysis: FMRIB Software Library (FSL) was used to perform between-group comparisons for each fMRI task versus rest in order to select regions of interest (ROIs). As previously reported, ROIs included subregions of the cingulate cortex and bilateral insula, and the right inferior gyrus pars opercularis [IFGop]; all ps<0.01, SVC; Kilroy et al., 2021;Jayashankar et al, 2024). Shotgun metagenomic sequencing of stool samples was performed. General Linear Models (GLMs) were applied in the ASD group to test brain-bacteria and bacteria-behavior relationships. Sex, age, IQ, and BMI were included as covariates. A false discovery rate of 10% (q<.10) was considered the threshold for reporting.
Results:
In ASD, activity in ROIs was significantly associated with abundance of different tryptophan-associated genera. Specifically, during observation of non-emotional faces, activity in the midcingulate was negatively related to Clostridium_A (standardized beta(β)=-0.44; q=0.07), while activity in the IFGop was positively linked to Ruminococcus_D abundance (β=0.40; q=0.09). Further, when processing disgusting foods, right mid-insula activity was related to Lactococcus_A_346120 ( β= -0.62; q= 0.04) and Ruminococcus_F (β= 0.62; q=0.03), while activity in the left ventral anterior insula was associated with Ruminococcus_F ( β=0.54, q=0.05). Additionally, activity in the left dorsal anterior insula during disgust facial expressions processing was related to Ruminococcus_D (Std. β=0.77; q=0.04).
Clostridium_T was significantly related to prenatal antibiotic usage (Std. β=-0.57, q=0.06), infant antibiotic usage (Std. β=-0.69 q=0.02), and delivery via c-section (β=-0.59 q=0.08), while Lactococcus_A_346120 was significantly related to sleep habits (β=-0.58, q=0.08).
Conclusions:
Alterations in the tryptophan pathway, including serotonin levels, have been previously linked to ASD symptomatology. This correlational study shows that the abundance of gut bacteria involved in tryptophan metabolism are related to activity in brain regions commonly known to differ in ASD (insula, cingulate, IFGop). Further, in ASD, these genera were related to early life factors (bacterial and antibiotic exposure, c-section delivery) and sleep habits. The findings provide support for the hypotheses that brain and behavioral differences in ASD may be associated with tryptophan-related genera.
Disorders of the Nervous System:
Neurodevelopmental/ Early Life (eg. ADHD, autism) 1
Emotion, Motivation and Social Neuroscience:
Social Cognition 2
Keywords:
Autism
Emotions
FUNCTIONAL MRI
Limbic Systems
Pediatric Disorders
Other - gut microbiome
1|2Indicates the priority used for review
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Please indicate below if your study was a "resting state" or "task-activation” study.
Task-activation
Healthy subjects only or patients (note that patient studies may also involve healthy subjects):
Patients
Was this research conducted in the United States?
Yes
Are you Internal Review Board (IRB) certified?
Please note: Failure to have IRB, if applicable will lead to automatic rejection of abstract.
Yes, I have IRB or AUCC approval
Were any human subjects research approved by the relevant Institutional Review Board or ethics panel?
NOTE: Any human subjects studies without IRB approval will be automatically rejected.
Yes
Were any animal research approved by the relevant IACUC or other animal research panel?
NOTE: Any animal studies without IACUC approval will be automatically rejected.
Not applicable
Please indicate which methods were used in your research:
Functional MRI
Other, Please specify
-
shot-gun metagenomics on stool samples
For human MRI, what field strength scanner do you use?
3.0T
Which processing packages did you use for your study?
FSL
Provide references using APA citation style.
Gabriele, S., Sacco, R., & Persico, A. M. (2014). Blood serotonin levels in autism spectrum disorder: A systematic review and meta-analysis. European neuropsychopharmacology, 24(6), 919-929. https://doi.org/10.1016/j.euroneuro.2014.02.004
Jayashankar, A., Kilroy, E., Ringold, S. M., Butera, C., McGuire, R., & Aziz-Zadeh, L. (2024). PREPRINT. Disgust processing differences and their neural correlates in autistic youth. https://doi.org/10.31234/osf.io/dt678
Kilroy E, Harrison L, Butera C, et al. Unique deficit in embodied simulation in autism: An fMRI study comparing autism and developmental coordination disorder. Human brain mapping. 2021;42(5):1532-1546. doi:10.1002/hbm.25312
Kang, D. W., Ilhan, Z. E., Isern, N. G., Hoyt, D. W., Howsmon, D. P., Shaffer, M., Lozupone, C. A., Hahn, J., Adams, J. B., & Krajmalnik-Brown, R. (2018). Differences in fecal microbial metabolites and microbiota of children with autism spectrum disorders. Anaerobe, 49, 121–131. https://doi.org/10.1016/j.anaerobe.2017.12.007
Needham BD, Adame MD, Serena G, et al. Plasma and Fecal Metabolite Profiles in Autism Spectrum Disorder. Biological psychiatry . 2021;89(5):451-462. doi:10.1016/j.biopsych.2020.09.025
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