Schistosoma mansoni infection enhances insertion sequence activity in the host gut microbiome

Abstract

Schistosoma mansoni infection is associated with alterations of the host gut microbial community structure, yet its impact on microbial genome dynamics and horizontal gene transfer remains poorly understood. In this study, we investigated the activity of Mobile Genetic Elements (MGEs), and of Insertion Sequences (IS) in particular, in the gut microbiome of wild-type (WT) and human-microbiota-associated (HMA) mice. Taxonomic profiling revealed significant differences in bacterial diversity between WT and HMA mice, with reduced richness and alpha diversity observed in HMA gut microbiomes regardless of the infection status. Principal Coordinates Analysis demonstrated clear separation between microbial communities, reflecting differences in host background and bacterial composition. In contrast, differences were observed between plasmid and viral community profiles and between these and bacterial diversity, suggesting that different MGEs may follow distinct ecological dynamics within the gut microbiome. IS elements within bacterial genomes were widespread across all microbiome communities analysed in this study, with higher insertion counts observed not only in HMA compared to WT mice, but also in infected compared to uninfected mice. IS elements were predominantly associated with dominant gut bacterial taxa, particularly members of Bacteroidia and Clostridia. At the genomic level, insertion events occurred more frequently in intergenic regions than in coding sequences, suggesting a preferential selective pressure towards alteration of gene expression rather than gene disruption. Furthermore, IS activity was dominated by a subset of IS families, with consistent patterns observed across experimental groups. Notably, infection was associated with increased insertion frequencies across multiple taxa and IS families, suggesting enhanced mobilisation under conditions of host-associated stress (the physiological and molecular pressure experienced by microorganisms, pathogens, or the host itself during their interactions within a symbiotic or infected environment) and microbiome perturbation. Together, these findings demonstrate that S. mansoni infection may promote IS mobilisation in the mouse gut microbiome, potentially contributing to microbial genome plasticity and facilitating horizontal gene transfer within host-associated microbial communities.