Functional Heterogeneity of the Autism Spectrum Disorder-Associated Gut Microbial Ecosystem Revealed by Fecal Lipopolysaccharides and Bacterial Proteomic Profiling.

Authors

Stefania De Chiara, Angela Di Somma, Valentina Mazziotti, Serena Coppola, Franca Oglio, Lidia Tammaro, Maria Pia Riccio, Carmela Bravaccio, Antonio Molinaro, Roberto Berni Canani, Flaviana Di Lorenzo

Published in

Chembiochem : a European journal of chemical biology. Volume 27. Issue 19. Pages e70557. Oct 14, 2026.

Abstract

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.

PMID:
42809586
Bibliographic data and abstract were imported from PubMed on 30 Sep 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.