Multiomics Integration Reveals Microbial Gene Interactions Shaping Host Responses in a DSS-Induced Colitis Mouse Model

Inflammatory bowel disease (IBD) has been studied with a multi-omics approach to identify key contributors and unravel the biological complexity of its pathogenesis, aiding in the development of early diagnostic markers and therapeutic targets. The dextran sulfate sodium (DSS)-induced colitis mouse model, a widely used system for studying IBD, induces gut barrier disruption and proinflammatory responses, making it an ideal model for investigating host-microbiome interactions. This study emphasizes the intricate relationship between microbial transcriptomic changes and host immune responses, revealing regulation of microbial genes, particularly in metabolic pathways related to carbohydrate metabolism, nucleotide metabolism, and aminoacyl-tRNA biosynthesis under inflammatory conditions. We identified key hub microbes and microbial genes that are closely associated with host immunological pathways, with particular focus on microbial aminoacyl-tRNA synthetases (aaRSs), which play significant roles in immune cell activation and inflammatory pathways. These findings offer valuable insights into the microbial contributions to inflammation and immune modulation in IBD, highlighting the potential role of aaRSs in regulating immune responses beyond their traditional function in translation. This lays the foundation for future research into host-microbiome interactions in inflammatory diseases and the development of novel therapeutic strategies that target microbial aaRSs to manipulate immune response.