biostudies-literatureAziz-Zadeh LNICHD NIH HHSNedra Gillette Endowed Research FellowshipU.S. Department of Health & Human Services | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)U.S. Department of DefenseU.S. Department of Defense (United States Department of Defense)U.S. Department of Health & Human Services | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development3465https://www.ebi.ac.uk/biostudies/studies/S-EPMC11997199biostudies-literatureUnknown16(1)While it has been suggested that alterations in the composition of gut microbial metabolites may play a causative role in the pathophysiology of autism spectrum disorder (ASD), it is not known how gut microbial metabolites are associated with ASD-specific brain alterations. In this cross-sectional, case-control observational study, (i) fecal metabolomics, (ii) task-based functional magnetic resonance imaging (fMRI), and (iii) behavioral assessments were obtained from 43 ASD and 41 neurotypical (NT) children, aged 8-17. The fMRI tasks used socio-emotional and sensory paradigms that commonly reveal strong evoked brain differences in ASD participants. Our results show that fecal levels of specific tryptophan-related metabolites, including kynurenate, were significantly lower in ASD compared tNature communicationsRelationships between brain activity, tryptophan-related gut metabolites, and autism symptomatology.PMC11997199R01 HD079432AR170062R01HD079432Tanartkit SJacobs JPBhatt RRRingold SMLabus JSAziz-Zadeh LDapretto MJayashankar AButera CMayer EAKilroy EMahurkar-Joshi SfalseRelationships between brain activity, tryptophan-related gut metabolites, and autism symptomatology.While it has been suggested that alterations in the composition of gut microbial metabolites may play a causative role in the pathophysiology of autism spectrum disorder (ASD), it is not known how gut microbial metabolites are associated with ASD-specific brain alterations. In this cross-sectional, case-control observational study, (i) fecal metabolomics, (ii) task-based functional magnetic resonance imaging (fMRI), and (iii) behavioral assessments were obtained from 43 ASD and 41 neurotypical (NT) children, aged 8-17. The fMRI tasks used socio-emotional and sensory paradigms that commonly reveal strong evoked brain differences in ASD participants. Our results show that fecal levels of specific tryptophan-related metabolites, including kynurenate, were significantly lower in ASD compared t2025-01-01T00:00:00Z2025 Apr2025-07-12T03:04:35.931Z2025-07-12T03:04:35.931ZS-EPMC119971994022923710.1038/s41467-025-58459-1