Longitudinal study of the gut microbiota in ulcerative colitis patients on anti-integrin biologic therapy

Abstract Disruptions of the gut microbiome are known to play a role in the pathophysiology of inflammatory bowel disease (IBD) and may influence response to biologic therapies. However, defining microbial signatures associated with treatment outcomes remains challenging. In this prospective longitudinal study, we analyzed changes in the intestinal microbiome of patients with active ulcerative colitis starting anti-integrin therapy with vedolizumab. Stool samples and clinical data were obtained at baseline and at weeks 12, 30, and 52 following treatment initiation. Microbial taxonomic composition and functional capacity were assessed using shotgun metagenomic sequencing. Patients who did not achieve clinical remission exhibited substantial interindividual heterogeneity in microbial composition and metabolic pathways throughout follow-up. In contrast, responders showed a more uniform and temporally stable microbiome, particularly during the induction phase. Importantly, none of the patients with markedly reduced baseline alpha diversity reached remission. Long-term responders demonstrated a gradual increase in commensal bacteria with reported anti-inflammatory effects, including Bacteroides uniformis, multiple Roseburia species (R. intestinalis, R. inulinivorans, R. faecis), and members of the Lachnospiraceae family. These microbial shifts were absent in non-responders and in patients who subsequently lost response. Taken together, these results indicate that baseline microbial diversity and longitudinal ecosystem stability may be associated with favorable response to anti-integrin therapy. Gut microbiome features could therefore complement clinical parameters in understanding treatment response and may contribute to future patient stratification strategies in ulcerative colitis.