Step-up fecal microbiota transplantation strategy: a pilot study for steroid-dependent ulcerative colitis

Abstract

Background: The strategy of using fecal microbiota transplantation (FMT) for refractory ulcerative colitis (UC) remains unclear if single FMT failed to induce remission. This study aimed to evaluate the efficacy and safety of a designed step-up FMT strategy for the steroid-dependent UC.

Methods: Fifteen patients with steroid-dependent UC were enrolled, and treated with step-up FMT strategy. Follow-up clinical data was collected for a minimum of 3 months. Fecal microbiota composition before and post FMT of patients and related donors were analyzed by 16S rRNA sequencing.

Results: Eight of fourteen (57.1 %) patients achieved clinical improvement and were able to discontinue steroids following step-up FMT. One patient was lost to follow-up. Among the 8 patients who responded, five (35.7 %) received one FMT therapy, one (7.1 %) received two FMTs, and two (14.2 %) received two FMTs plus a scheduled course of steroids. Four (28.6 %) of the 8 patients who responded maintained long-term remission during follow-up (3-18 months). Six patients (42.9 %) failed to meet the criteria of clinical improvement and maintained steroid dependence, though three experienced transient or partial improvement. Microbiota analysis showed that FMT altered the composition greatly, and a microbiota composition highly similar to that of the donor emerged in the patients with successful treatment. No severe adverse events occurred during treatment and follow-up.

Conclusions: Step-up FMT strategy shows promise as a therapeutic strategy for patients with steroid-dependent UC, likely due to the successful restructuring of gut microbial composition.

Trial registration: ClinicalTrials.gov, Number NCT01790061.

Figures

Fig. 1

Laboratory enriched fecal microbiota and infusion of fecal microbiota during endoscopy. a The centrifuged microbiota in lab after microfiltration. b The final product for infusion. c, d The endoscopic image during infusion showing no observable particles in the suspension fluid under magnified endoscopic view, indicating the effect of purification for fecal microbiota

Fig. 2

Flow chart of step-up FMT for steroid-dependent UC. The strategy includes three steps: 1 the initial FMT; 2 a second FMT after 1 week; 3 one short course of steroid therapy. Patients who fail to benefit from step 1 are advised to receive the second FMT. Patients who still had no response were switched to one-phase therapy using steroids. Withdrawal of corticosteroid started after 2–4 weeks of full dose of steroids. The patients who failed to benefit from each step could also choose biologic therapy or resumption of steroid therapy

Fig. 3

Clinical response to step-up FMT. a Abdominal pain scores of patients with steroid-dependent UC at baseline and the first week after initial FMT (n = 15). 10 patients showed significant improvement of abdominal pain after FMT. b Abdominal pain score at baseline and throughout follow-up after step-up FMT (n = 15); c frequency of patients’ defecation before and at 1 week after initial FMT (n = 15), 12 patients showed improvement in stool frequency; d change in defecation frequency at baseline and throughout follow-up after step-up FMT (n = 15)

Fig. 4

Analysis of fecal microbiota of patients with steroid-dependent UC. a The diversity of fecal microbiota (Shannon’s diversity index) showed significant decrease in steroid-dependent UC compared with healthy donors (*P < 0.05); b fecal microbiota composition at the phylum level in patients with steroid-dependent UC and in healthy donors

Fig. 5

Change of fecal microbiota composition after FMT at a phylum level. a The schedule of fecal sample collection; b change in Shannon’ diversity index before and after FMT; c analysis of fecal microbiota composition at the phylum level before and after FMT

Fig. 6

Genus level change in fecal microbiota composition following (two) FMTs in ulcerative colitis patients who are steroid-dependent

Fig. 7

Similarity of fecal microbiota composition at the genus level. a Changes in Pearson correlation coefficient at the genus level. Pearson correlation coefficient ranged from 0 (red) to 1 (green). When the value between two samples is close to 1, the compositions are more similar. b Principal coordinate analysis (PCoA) of (Unifrac distance between) fecal microbiota before and after FMT. The distance between the samples represents the similarity of micobiota composition; a closer distance indicates higher similarity. Patient 6 and patient 10 shared the same donor (donor 1)