Abstract
Multiple Sclerosis (MS) is a chronic demyelinating immune disease with rising global prevalence, and depression represents one of its most common comorbidities. Both MS and depression have been independently associated with gut microbiome perturbations, however the extent to which MS disease severity and depressive status jointly modulate microbial diversity and taxonomic structure remains unresolved. Using a paired household 16S rRNA dataset, we performed an integrative analysis of alpha and beta diversity, core microbiome membership, and differential abundance across six experimental groups differentiated by MS severity (RRMS, PMS) and depression presence. Alpha diversity analyses indicated that richness differed significantly in PMS patients with or without depression, while Beta diversity analysis confirmed this and revealed additional significant comparisons between several MS and depression groups. In contrast, taxonomic composition remained comparatively stable across groups and abundance only differed exclusively in the PMS group and in two species, Varibaculum cambriense and Blautia fusiformis. The divergence between distinct diversity effects and minimal taxonomic shift implies that rare taxa abundance may disproportionately contribute to observed diversity patterns.