Microbial Signal Recognition & Neuronal Mimicry (SRNM) axis in IBD

BackgroundInflammatory bowel disease (IBD) is a chronic inflammatory disorder characterized by gut microbial dysbiosis and immune dysregulation. While compositional changes in the microbiome are well studied, the functional mechanisms through which microbes influence host signalling remain poorly understood. PurposeThis study aimed to investigate microbial-host molecular mimicry in IBD and to elucidate its role in modulating immune and neuronal pathways through a newly proposed Microbial Signal Recognition and Neuronal Mimicry (SRNM) axis. MethodsShotgun metagenomic datasets from IBD patients and healthy controls were analyzed using a custom Molecular Mimicry In Silico Pipeline (MMIP). Reads were assembled, annotated, and subjected to protein homology mapping, Gene Ontology enrichment, PFAM domain analysis, and taxonomic profiling to identify microbial proteins mimicking human functional pathways. ResultsIBD-associated microbiomes exhibited significantly higher functional complexity and enrichment of eukaryote-like proteins compared to healthy controls. Microbial proteins mimicking host pathways involved in neuron projection development, signal recognition particle (SRP)-mediated protein targeting, immune signaling, and stress responses were markedly enriched in IBD. Key human-like targets included TRPV1, CAMK2D, SNCA, MTCP1, TCL1B, and PEAK3. PFAM analysis revealed overrepresentation of kinase domains, zinc-finger motifs, ankyrin repeats, and ABC transporters. These signatures were predominantly contributed by IBD-enriched taxa such as Gammaproteobacteria, Fusobacteria, and Betaproteobacteria. ConclusionThis study identifies a previously unrecognized SRNM axis in IBD, revealing how microbial molecular mimicry may influence neuroimmune signaling and disease pathogenesis, and highlight potential targets for microbiome-based therapeutic intervention.