Functional Gut Microbiota Alterations in Patients with Inflammatory Bowel Disease Receiving Long-Term Biologic Therapy: A Pilot Comparative Study.

Background: Biological therapies have substantially improved clinical outcomes in inflammatory bowel disease (IBD); however, the relationship between long-term biologic therapy, disease remission, and gut microbiome characteristics remains incompletely understood. This pilot study aimed to characterize the taxonomic composition and taxonomically inferred functional microbiome features of patients with IBD receiving long-term biologic therapy and achieving clinical and biological remission at the time of microbiome assessment. Methods: Patients with IBD receiving long-term biologic therapy and achieving clinical and biological remission at the time of microbiome assessment were prospectively enrolled. Gut microbiome composition was assessed using 16S rRNA gene sequencing. Functional microbiome profiling included microbial diversity (Shannon index), fecal pH, Firmicutes/Bacteroidetes ratio, and bacterial groups associated with short-chain fatty acid production, mucin degradation, and lipopolysaccharide (LPS) production. Comparative analyses between disease phenotypes and biologic therapies were performed using non-parametric statistical methods. Results: Fifteen patients with IBD were included, comprising eight patients with ulcerative colitis and seven with Crohn's disease. Several microbiome features were outside the laboratory-specific reference intervals despite clinical and biological remission at the time of microbiome assessment. Shannon diversity values were below the laboratory-specific reference threshold in 60.0% of patients, while taxa associated with mucin degradation, lactate production, and LPS production were outside the respective reference intervals in 66.7%, 53.3%, and 46.7% of patients. The Firmicutes/Bacteroidetes ratio was outside the reference interval in 46.7% of patients. The gut microbiota was predominantly composed of Firmicutes and Bacteroidetes, with considerable interindividual variability in taxonomic composition and taxonomically inferred functional features. No statistically significant differences were identified between Crohn's disease and ulcerative colitis or between biologic therapies after false discovery rate correction. Conclusions: Patients with IBD receiving long-term biologic therapy and achieving clinical and biological remission at the time of microbiome assessment exhibited substantial interindividual variability in taxonomic composition and taxonomically inferred functional microbiome features. Several parameters were outside laboratory-specific reference intervals; however, the cross-sectional design and absence of pre-treatment and matched healthy control samples preclude conclusions regarding microbiome restoration or treatment-related effects. These findings support further longitudinal investigation of microbiome characteristics during biologic therapy.