Mo1806 THE EFFECT OF VEDOLIZUMAB ON COLONIC MICROBIOTA COMPOSITION IN PATIENTS AFFECTED BY INFLAMMATORY BOWEL DISEASE

Backgrounds: The complex interaction between gut microbiota, intestinal epithelium integrity and host immune system appear to be the most involved pathological mechanism in Inflam- matory Bowel Diseases (IBD) pathogenesis. In this study, the effect of Vedolizumab (VDZ) treatment on gut microbiota composition was evaluated in IBD patients with moderate- severe disease activity. Materials and Methods: 18 IBD patients (CD: 28%; UC: 72%) undergo- ing VDZ treatment, were enrolled. Clinical remission and clinical response were assessed by Harvey-Bradshaw Index (HBI) and Partial Mayo Score (PMS) for CD and UC respectively. During a colonoscopy performed before (T0), after 24 weeks (T1) and after 52 weeks of treatment (T2), the disease activity was evaluated by standardized scores (SES-CD and Mayo Endoscopic Subscore) and four colonic biopsies were collected for gut microbiota analysis. In the same time-points fresh faecal samples were collected for the microbiota analysis performed by 16S rRNA Sequencing workflow (Illumina). Results: The clinical response and the remission rates at week 52 were respectively 73% and 45% in UC patients [PMS, T0-T1-T2: p=0.0002] and both 100% in CD patients [HBI, T0-T1-T2: p=0.0221]. A positive endoscopic response (Mayo Endoscopic Subscore reduction ≥1; T0-T1-T2: p=0.0355) was observed in 55% of UC patients at week 52. In biopsy samples, α-diversity showed a significant increase over time after VDZ treatment, compared to baseline [p=0.021]. Compar- ing the distribution of bacterial OTUs at T0 and T1, an increase of SCFAs-producing bacterial taxa belonging to the Firmicutes phyla (Ruminococcaceae, Lachnospiraceae, Blautia) was observed. A reduction of bacterial species with potential pro-inflammatory activity belonging to Proteobacteria phyla (Enterobacteriaceae, Pasteurellaceae, Streptococcaceae, Veillonella- ceae and Clostridium spp) at 24 and 52 weeks of follow-up was observed. Comparing the distribution of OTUs from T0 to T1, a positive trend of Firmicutes, Lachnospiraceae and Ruminococcaceae was observed, with a concomitant decrease in Enterobacteriaceae and Clostridiaceae. After 52 weeks of VDZ treatment, a partial restoration of beneficial bacterial species producing SCFAs, such as Rikinellaceae and Bifidobacterium spp, was observed in faecal sample. Conclusions: Treatment with Vedolizumab showed a reduction of the local pro-inflammatory microbial state, an effect associated with an improvement in clinical conditions. Further investigation will be necessary to determine whether these modifications could contribute to the maintenance of remission in IBD patients following treatment.