Streptococcus mutans exacerbates gut microbiota dysbiosis in SHANK3 -/- autism model mice via the oral-gut axis.

Abstract

Background and objective: Autism spectrum disorder (ASD) is associated with gut microbiota dysbiosis, yet the impact of oral pathobiont translocation via the oral-gut axis remains unclear. This study investigated how Streptococcus mutans (S. mutans), a primary cariogenic pathogen, influences gut microbial structure and function in an ASD mouse model.

Methods: SHANK3 knockout (SHANK3^-/-) and wild-type (WT) mice were divided into four groups: WT control, WT S. mutans-gavaged (WT-S.m), SHANK3^-/- control, and SHANK3^-/- S. mutans-gavaged (SHANK3-S.m). Mice were gavaged with S. mutans UA159 twice weekly for five weeks, followed by fecal metagenomic sequencing (n = 6 per group).

Results: S. mutans translocated to the gut in both gavaged groups but did not achieve enhanced colonization in SHANK3^-/- mice. S. mutans gavage significantly altered the gut microbiota structure in both WT and SHANK3^-/- mice. In the ASD model, S. mutans gavage led to a significant enrichment of potential pathobionts (e.g. Duncaniella dubosii, Muribaculum gordoncarteri) and a decrease in beneficial bacteria (e.g. Bacteroides caecimuris, Bacteroides faecium). LEfSe analysis identified Parascardovia denticolens and Bacteroides heparinolyticus as specific biomarkers for the SHANK3-S.m group. Microbial networks showed reduced stability in SHANK3-S.m mice, with Enterocloster bolteae as a key node. Functional analysis revealed suppressed butanoate metabolism and enhanced neuroinflammation-related pathways.

Conclusion: Although S. mutans colonized only transiently, it provoked exacerbated ecological instability and pro-inflammatory metabolic alterations in ASD model mice, underscoring the role of the oral-gut-brain axis in ASD.