Exploring the Differential Host Responses to DSS and UC-Derived Microbiota in a Mouse Model of Colitis

Ulcerative colitis is a chronic inflammatory condition of the colon characterised by recurring mucosal inflammation. Current evidence suggests that dysbiosis may drive the disease but mechanistic links remain incompletely understood. To further investigate the host and microbiome interactions, three methods to induce UC in mice were used. DSS, microbiome from a patient with UC, administered as faecal microbiota transplantation, and a combination of both induction methods. Disease severity, immune cell profiles, colon transcriptomics and microbiota composition were assessed. Our study revealed distinct effects of DSS and FMT on experimental colitis. DSS had a more pronounced impact on disease severity, while FMT exerted a stronger influence on several immune populations and downregulation of genes associated with tight junctions and mucins. Microbiome analysis demonstrated distinct compositional profiles across all experimental groups. The combined FMT and DSS model exhibited features of both induction methods, resulting in exacerbated clinical scores, barrier dysfunction, and inflammatory responses. Our study provides valuable insight into host and microbiome interactions in UC and introduces a new approach that may more accurately recapitulate its multifactorial pathogenesis than DSS alone.