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

J Landy,P J Ciclitira,D Bernardo,S C Knight,S D Mclaughlin,H O Al-Hassi,J V Li,A W Walker,N R English,S K Clark,J Parkhill,E R Mann,E Ronde,A L Hart

doi:10.1038/srep12955

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.

Highlights

Yes No No Yes No No Yes Yes intestinal inflammation occurs in the ileal reservoir after a restorative proctocolectomy (RPC) for ulcerative colitis (UC)
We report the first study of Faecal microbiota transplantation (FMT) in patients with chronic pouchitis that incorporates clinical, immunological, and both taxonomic and functional microbiological assessments
Our study suggests that administration of a single nasogastrically delivered FMT from a healthy donor results in some shift in the composition of the microbiota, and in some cases with specific changes in the abundance of species suggestive of a “healthier” pouch microbiota

Summary

Introduction

Yes No No Yes No No Yes Yes intestinal inflammation occurs in the ileal reservoir after a restorative proctocolectomy (RPC) for ulcerative colitis (UC). Clinical data confirm a role for antibiotics and probiotics for the treatment of acute and chronic pouchitis[8,9,10,11,12,13,14]. Recent studies of FMT in UC did not demonstrate clinical efficacy and suggest variable efficiency of colonisation by the donors’ microbiota[24,25]. Probiotics and prebiotics have been shown to alter mucosal innate and adaptive immune responses, DC function, in IBD30–32. We hypothesised that FMT would induce clinical response in patients with chronic pouchitis, altering the composition and function of the pouch microbiota and elicit immunoregulatory effects. We aimed to assess the effect of FMT on the microbiota composition and function, in addition to effects on the mucosal immune response, on DC, and assess the clinical response in patients with chronic pouchitis

Objectives

Methods

Conclusion