Promise of Fecal Microbiota Transplantation Therapy in Pouchitis

Abstract

Although restorative proctocolectomy with ileal pouch–anal anastomosis (IPAA) is an important surgical treatment for medically refractory ulcerative colitis, it is frequently complicated by pouchitis, a condition responsible for up to 8.5% of pouch failures [1]. Though pouchitis comprises a spectrum of heterogenous disorders with diverse risk factors, clinical presentations, and prognoses, pouch dysbiosis appears to underlie initiation and progression of most forms of the disease [2]. While conducting a comprehensive meta-analysis to evaluate the efficacy of fecal microbiota transplantation (FMT) in IBD subtypes, we reported clinical remission in 21.5% (5/23) of patients with pouchitis who underwent FMT [3]. These analyses, however, were descriptive since only three small cohort studies with differing infusion regimens, endpoints, and conflicting outcomes were identified at the time [4–6]. In this issue of Digestive Diseases and Sciences, Selvig et al. [7] report on the largest study of FMT therapy in pouchitis to date. While post-FMT Pouchitis Disease Activity Index (PDAI) scores were not available for all patients and some had PDAI scores ≤ 6 pre-FMT [7], the slight improvements in endoscopic and histological outcomes are supported by the only other pouchitis study reporting these data. Specifically, Stallman et al. reported endoscopic response in all patients (n = 5) and endoscopic remission in one patient (20%) following FMT infusions (n = 1–7 instillations) [6]. Selvig et al. [7] also report statistically significant improvement in bowel frequency, which was particularly evident in patients receiving rifaximin pre-FMT and a second FMT instillation. These observations align well with a recent report of severe diversion ileitis and pouchitis in a patient with a history of ulcerative pancolitis, in whom multiple autologous FMT infusions were required for successful treatment, leading to an increase in Firmicutes and decrease in Proteobacteria in the ileal pouch [8]. At present, with respect to FMT for pouchitis, there is a paucity of available data, a high degree of heterogeneity among studies, and lack of randomized controlled trials for either induction or maintenance (Table 1) [4–7, 9, 10]. Though the study by Selvig et al. [7] provides further patient data, clarity is still missing in many aspects. The use of antibiotics (rifaximin) pre-FMT in pouchitis is interesting, although its impact is unclear as only a small subset of patients received this treatment (7/19). Assessment of clinical efficacy is also limited by inconsistency in the number of FMT infusions provided. Of the eleven patients receiving two FMT infusions, six received rifaximin. The current literature strongly suggests that the use of antibiotics pre-FMT in UC patients assists in the engraftment of beneficial xenomicrobiota, improving clinical and histological responses [3, 11]. Indeed, a recent prospective randomized placebo-controlled double-blind FMT trial in patients with pouchitis was stopped prematurely due to low donor FMT engraftment [10]. Given that antibiotic therapy is the primary treatment modality in pouchitis, the use of antibiotics pre-FMT in this context is promising but only if an adequate selection of antibiotics, dosage, and length of therapy are ensured. Profiling of the bacteriome showed that communitylevel differences were restricted to comparisons between donors and patients with pouchitis regardless of FMT, with donors showing higher phylogenetic diversity [7]. No shifts in patients’ community profiles toward donor profiles were evident, unlike previous studies examining FMT in pouchitis [5, 6]. Selvig et al. [7] identified specific bacterial taxa * Natalia Castaño-Rodríguez [email protected]