Variable alterations of the microbiota, without metabolic or immunological change, following faecal microbiota transplantation in patients with chronic pouchitis

Abstract

Faecal microbiota transplantation (FMT) is effective in the treatment of Clostridium difficile infection, where efficacy correlates with changes in microbiota diversity and composition. The effects of FMT on recipient microbiota in inflammatory bowel diseases (IBD) remain unclear. We assessed the effects of FMT on microbiota composition and function, mucosal immune response, and clinical outcome in patients with chronic pouchitis. Eight patients with chronic pouchitis (current PDAI ≥7) were treated with FMT via nasogastric administration. Clinical activity was assessed before and four weeks following FMT. Faecal coliform antibiotic sensitivities were analysed, and changes in pouch faecal and mucosal microbiota assessed by 16S rRNA gene pyrosequencing and 1H NMR spectroscopy. Lamina propria dendritic cell phenotype and cytokine profiles were assessed by flow cytometric analysis and multiplex assay. Following FMT, there were variable shifts in faecal and mucosal microbiota composition and, in some patients, changes in proportional abundance of species suggestive of a “healthier” pouch microbiota. However, there were no significant FMT-induced metabolic or immunological changes, or beneficial clinical response. Given the lack of clinical response following FMT via a single nasogastric administration our results suggest that FMT/bacteriotherapy for pouchitis patients requires further optimisation.

Combined Endoscopic and Oral Fecal Microbiota Transplantation in Patients with Antibiotic-Dependent Pouchitis: Low Clinical Efficacy due to Low Donor Microbial Engraftment

“…The reason for the low engraftment in our study could be due to several factors, including donor selection, the dose and frequency of FMT, and the pouch microenvironment. The low donor engraftment found in our study may also explain the inconsistent and partially contradictory results of the other small controlled and uncontrolled observations of FMT in patients with chronic refractory pouchitis or ADP [8, 17]. Further studies need to determine the mechanisms of engraftment in the small bowel environment.…”

Consensus report: faecal microbiota transfer – clinical applications and procedures

“…A number of case studies showing positive effects of FMT in IBD have been published . However, most of these studies involve low patient numbers, are mostly published in abstract form, and might be subjected to publication bias.…”

Intestinal microbiota, fecal microbiota transplantation, and inflammatory bowel disease

“…122,123 Although this suggests that FMT may also be a treatment of pouchitis, small studies have failed to demonstrate remission following FMT. 124 One key limitation in FMT for pouchitis is the size of the pouch, which may limit engraftment of a donor microbiota. Although current data are not promising, more data are necessary to understand the effects of FMT on pouchitis.…”