Long-term efficacy and safety of monotherapy with a single fresh fecal microbiota transplant for recurrent active ulcerative colitis: a prospective randomized pilot study

Abstract

Background: To assess the long-term safety and efficacy of monotherapy with a single fresh fecal microbiota transplant (FMT) for recurrent ulcerative colitis (UC).

Results: Twenty-six eligible patients were enrolled, and 6 patients were excluded. Ultimately, 20 patients were randomized to the FMT group (n = 10) and the control group (n = 10); 80% were females (F/M = 16/4), the mean age was 48 ± 14 years, and the mean duration was 6.4 ± 8.2 years. The mean length of post-FMT follow-up was 19.1 ± 10.1 months (6-38). No statistically significant differences in baseline demographic or clinical characteristics were found between the groups. Ninety percent of patients in the FMT group and 50% of patients in the control group met the primary endpoint at week 8. The Mayo score was significantly decreased compared with that of the control group (n = 10) when reassessed at week 4 (P = 0.001) and week 8 (P = 0.019) after FMT; there was no significant difference 6 months after treatment. The median remission time was 24 months (95% CI 68.26-131.7%) in both the FMT (range 6-38 months) and control groups (range 7-35 months), with no significant difference (P = 0.895). Participants tolerated FMT treatment, and no adverse events occurred during long-term follow-up, with one treatment-related significant adverse event (EBV infection) occurring within 2 weeks after FMT. Stool microbiota composition analysis indicated improved gut microbiota diversity after FMT, with expansion of stool-donor taxa. Bacteroidetes, Firmicutes and Proteobacteria were the dominant bacterial phyla of the gut microbiota in active UC patients. The relative abundance of Bacteroidetes decreased and that of Proteobacteria increased significantly in active UC patients compared with donors, while Firmicutes showed no significant changes. A single fresh FMT could effectively reconstruct the gut microbiota composition in patients with active UC and maintain stability, with increased Bacteroidetes and decreased Proteobacteria abundance. FMT significantly reduced the relative abundance of Escherichia and increased the relative abundance of Prevotella at the genus level. Pyruvate metabolism, glyoxylate and dicarboxylate metabolism, and pantothenate and CoA biosynthesis showed significant differences after transplantation.

Conclusions: Monotherapy with a single fresh FMT is an effective and safe strategy to induce long-term remission without drugs in patients with active UC and may be an alternative induction therapy for recurrent UC or even primary UC.

Keywords: Fecal microbiota transplantation; Gut microbiota; Inflammatory bowel disease; Intestinal flora; Ulcerative colitis.

Fig. 1

Clinical response to FMT monotherapy (FMT group) and routine therapy (control group) after two weeks of treatment. a Abdominal pain score of patients with active UC at baseline and 2 weeks after treatment. In the FMT group, the value was 4.5 ± 2.2 at baseline and 0.9 ± 1.6 after FMT monotherapy (n = 10). In the control group, the values were 4.9 ± 2.1 at baseline and 1.8 ± 1.3 after routine therapy (n = 10). Compared with that observed in pretreatment, abdominal pain significantly improved after FMT treatment and routine therapy (^* P = 0.000). b Diarrheal frequency of patients with active UC at baseline and 2 weeks after FMT monotherapy. In the FMT group, the value was 8.8 ± 3.8 at baseline and 2.5 ± 2.7 after FMT monotherapy (n = 10). In the control group, the values were 7.8 ± 3.1 at baseline and 3.3 ± 1.0 after routine therapy (n = 10). Compared with that observed in pretreatment, diarrheal frequency significantly improved after FMT treatment and routine therapy (^# P = 0.000)

Fig. 2

Long-term efficacy of FMT monotherapy or routine therapy for recurrent active UC. a Mayo scores at baseline (pretreatment) and post-treatment at week 4 and week 8 in the two groups. Compared with the control group (n = 10), the baseline value showed no significant difference (* P = 0.899), while the value was significantly decreased when reassessed at week 4 (# P = 0.001) and week 8 (## P = 0.019) after FMT treatment (n = 9 FMT responders). b Mayo scores after long-term follow-up in the two groups; the scores were not significantly different between the two groups when reassessed after 6 months (P = 0.691). c Fresh FMT monotherapy resulted in a median of 24 months (range, 6–38) of remission. Routine therapy also achieved a median of 24 months (range, 7–35) remission (95% CI 68.26–131.7%). Monotherapy with a single fresh FMT can achieve long-term remission without drugs in patients with recurrent active UC. There was no significant difference in the maintenance of remission in patients treated with a single FMT compared with the control patients (P = 0.895), but patients with active UC who received FMT seemed to achieve clinical remission more quickly

Fig. 3

Endoscopic appearance of pancolitis pre- and post-FMT treatment after long-term follow-up in patients with recurrent active UC. The endoscopic appearance includes mucosal hyperemia and edema, mucous exudate erosions, multiple ulcers and spontaneous bleeding in the ileocecum (a), ascending colon (b), sigmoid colon (c) and rectum (d) before FMT therapy. Markedly improved lesions with normal mucosa were observed at 24 months after a single fresh FMT. A single fresh FMT can achieve long-term remission without drugs and no obvious adverse events in patients with recurrent active UC

Fig. 4

Stool microbiota composition analysis. a Alpha diversity index box chart The abscissa represents sample grouping, and the ordinate is the alpha index. The healthy donors, active UC patients (marked as pretreatment) and patients post FMT treatment (marked as posttreatment) showed no significant difference (p > 0.05). b Venn diagram indicating the number of differential OTUs in each group. c Analysis of similarities (ANOSIM) showed significant differences among the healthy donors and pretreatment and posttreatment UC patients. d Principal coordinate analysis (PCoA) of the gut microbiota among the healthy donors, active UC patients and patients post FMT treatment. The distance between the samples represents the similarity of the gut microbiota composition, and a closer distance indicates higher similarity. e Nonmetric multidimensional scaling plots (NMDS) of the gut microbiota among the healthy donors, active UC patients and patients post-FMT treatment

Fig. 5

Histogram of taxonomic profiles of the gut microbiota among healthy donors, active UC patients (marked as pretreatment) and patients post-FMT treatment (marked as post-treatment) LDA score (a), cladogram (b) and profiles at the phylum (c), genera (d) and species level. Prevotella was the dominant genus in the gut microbiota of the healthy donors, and the relative abundance of Prevotella increased after FMT treatment in active UC patients