Implications of oral streptococcal bacteriophages in autism spectrum disorder

Abstract

Growing evidence suggests altered oral and gut microbiota in autism spectrum disorder (ASD), but little is known about the alterations and roles of phages, especially within the oral microbiota in ASD subjects. We enrolled ASD (n = 26) and neurotypical subjects (n = 26) with their oral hygiene controlled, and the metagenomes of both oral and fecal samples (n = 104) are shotgun-sequenced and compared. We observe extensive and diverse oral phageome comparable to that of the gut, and clear signals of mouth-to-gut phage strain transfer within individuals. However, the overall phageomes of the two sites are widely different and show even less similarity in the oral communities between ASD and control subjects. The ASD oral phageome exhibits significantly reduced abundance and alpha diversity, but the Streptococcal phages there are atypically enriched, often dominating the community. The over-representation of Streptococcal phages is accompanied by enriched oral Streptococcal virulence factors and Streptococcus bacteria, all exhibiting a positive correlation with the severity of ASD clinical manifestations. These changes are not observed in the parallel sampling of the gut flora, suggesting a previously unknown oral-specific association between the excessive Streptococcal phage enrichment and ASD pathogenesis. The findings provide new evidence for the independent microbiome-mouth-brain connection, deepen our understanding of how the growth dynamics of bacteriophages and oral microbiota contribute to ASD, and point to novel effective therapeutics.

Alterations in fecal virome and bacteriome virome interplay in children with autism spectrum disorder

“… 45 Zhan Tong et al. reported that Streptococcal phages were significantly enriched in the mouths of children with ASD, 46 and consistently, there are 4 gut Streptococcal phages ( Figure S2 A) that were identified as ASD-enriched phages in our analysis. Streptococcus and the interplay with its phages may affect normal brain normal function via releasing inflammatory signals.…”

“…Streptococcus and the interplay with its phages may affect normal brain normal function via releasing inflammatory signals. 46 , 47 …”

Microbiota in Autism Spectrum Disorder: A Systematic Review

“…In one of the papers, lowered bacterial diversity was observed, similar to the gut microbiota. The iterative results included higher abundance of Rothia (67%) [39,40] (although one of the papers observed such a trend only in dental samples), Streptococcus (67%) [39,47], and Proteobacteria (67%) (specifically Haemophilus) [39,40], and lower abundance of Firmicutes (67%) [39,40] and Fusobacteriota (67%) [39,40]. Higher abundance of Moryella correlated with better verbal skills and a lower occurrence of early autism symptoms.…”

SVep1, a temperate phage of human oral commensal Streptococcus vestibularis

“…Additionally, the temperate phage YMC-2011 of Streptococcus salivarius has been isolated and identified ( Chou et al, 2017 ). Recently, a potential prophage from S. vestibularis was described in the oral flora of children with autism ( Tong et al, 2022 ). However, no phage from S. vestibularis has been isolated and characterized thus far.…”