Changes in Microbial Ecology After Fecal Microbiota Transplantation for Recurrent C. Difficile Infection Depends on Underlying Inflammatory Bowel Disease: 2016 ACG Presidential Poster Award

Abstract

Introduction: Alterations in the gut microbiota predispose to Clostridium difficile infection (CDI) and are associated with inflammatory bowel disease (IBD). Fecal microbiota transplantation (FMT) effectively treats CDI and is being investigated for its ability to treat IBD. In this study, we investigated changes in gut microbiota following FMT in CDI patients with or without underlying IBD. Methods: Patients with recurrent CDI were enrolled and a fecal sample was obtained prior to FMT, day 7 and 28 post-FMT. V4 region of 16S rRNA gene was used for gut microbiota profiling using the MISEQ Illumina platform and data analyses were performed using QIIME. Results: Overall 38 CDI patients (12 with IBD) were included (Table 1). All patients responded to FMT, symptoms returned to baseline in 35; 2 IBD patients had worsening C. difficile -ve diarrhea & 1 had new onset constipation. At 2-year follow-up 5 had another CDI episode & 4 required 2nd FMT due to multiply recurrent CDI. The risk of future CDI after FMT in IBD patients was 25% vs 7.7% in non-IBD patients (p=0.16). None of the IBD patients improved IBD course or were able to withhold or de-escalate treatment.Table 1FMT led to a significant increase in alpha diversity based on Faith's phylogenetic diversity, Shannon's diversity index and observed species, at day 7 & day 28 (p < 0.05). A sustained change in unweighted and weighted UniFrac-based beta diversity following FMT at day 7 and 28 post-transplant was seen (p < 0.05) independent of underlying IBD. The Microbial Dysbiosis (MD) index values were significantly higher in patients with CDI compared to donors (p < 0.05) independent of underlying IBD. Microbial communities from all CDI patients were distinct from donor communities prior to FMT (Spearman's r>0.4 for 85% patients). Using SourceTracker, patients with IBD retained a higher proportion of their original microbial communities after FMT (p < 0.05 at day 7, and p = 0.06 at day 28) and significantly lower proportion of the new communities (p < 0.05 at day 7 and 28) compared to those without IBD. Conclusion: FMT led to a significant increase in microbial diversity in patients with recurrent CDI. CDI patients with IBD had a higher proportion of the original community after FMT and lack of improvement of their IBD course. Changes in gut microbial landscape may be important for long-term success of CDI treatment in patients with underlying IBD and potentially for improvement of IBD course.