Chembiochem : a European journal of chemical biologySep 29, 2026

Different Functions of the Gut Microbial Community Linked to Autism Revealed by Stool Bacterial Molecules and Proteins

Gut-Brain Axis Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Sep 30, 2026

Abstract

Altered inflammatory molecular outputs may be associated with gut microbiota in children with autism spectrum disorder (ASD).

LPS from non-autistic healthy donors showed conserved carbohydrate and lipid A signatures, typically linked to immunomodulatory bacteria.
In contrast, LPS from ASD children exhibited increased structural heterogeneity.
ASD-derived fecal LPS induced stronger release of IL-6 and IL-8 in human microglial cells compared to LPS from healthy donors.
Despite similar microbial compositions, there was marked metabolic divergence in gut microbiota between ASD and non-ASD children.
Findings indicate a functionally heterogeneous microbial ecosystem in ASD children, associated with altered immunostimulatory outputs.

Simplified

The etiology of pediatric autism spectrum disorder (ASD) has been increasingly linked to alterations in the gut-brain axis, highlighting the intricate bidirectional communication between gut microbiota and central nervous system. The molecular mechanisms of this communication are poorly understood. Here we investigated whether ASD-associated gut microbiota could exhibit altered inflammatory molecular outputs by integrating chemistry-driven profiling of fecal lipopolysaccharides (LPS), functional bacterial proteomics, and neuroimmune cellular assays. Structural analyses revealed that LPS from non-autistic healthy donors (NASD) displayed highly conserved carbohydrate and lipid A signatures dominated by hypo-acylated mono-phosphorylated species typically associated with immunomodulatory Bacteroides-derived LPS. In contrast, LPS from ASD children exhibited increased structural heterogeneity. These molecular alterations were functionally reflected in human HMC3 microglial cells, where ASD-derived fecal LPS induced stronger IL-6 and IL-8 release compared with NASD-derived LPS, indicating enhanced neuroinflammatory potential. Functional proteomic profiling disclosed broadly comparable microbial compositions but marked metabolic divergence. These findings suggest that gut microbiota in ASD children are associated with a functionally heterogeneous microbial ecosystem characterized by altered immunostimulatory molecular outputs despite the absence of massive taxonomic shifts, with potential relevance for neuroimmune dysregulation.

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Different Functions of the Gut Microbial Community Linked to Autism Revealed by Stool Bacterial Molecules and Proteins

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