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

Haiming Fang,Kangwei Xiong,Xuejun Li,Chunxia Lu,Lian Fu,Lijiu Zhang,Yuan Su

doi:10.1186/s12934-021-01513-6

Abstract

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

Highlights

Ulcerative colitis (UC), a major subtype of inflammatory bowel disease (IBD), is characterized by chronic recurrent colorectal mucosal inflammation
Demographic and clinical characteristics Twenty-six eligible patients who were diagnosed with recurrent active ulcerative colitis (UC) were enrolled in this study, and 6 patients were excluded (4 did not meet the inclusion criteria, and 2 declined to participate)
The patients were randomized to the fecal microbiota transplant (FMT) monotherapy group (n = 10) and the control group (n = 10)

Summary

Introduction

Ulcerative colitis (UC), a major subtype of inflammatory bowel disease (IBD), is characterized by chronic recurrent colorectal mucosal inflammation. Deregulation of immunological responses and intestinal barrier dysfunction, dysbiosis of the gut microbiota and external environmental triggers have been identified as key pathogenic factors for UC. IBD has become a global health burden with increasing incidence and prevalence. The incidence and prevalence of UC vary in different regions and are highest in Western countries. With the Western diet and lifestyle, as well as the widespread use of antibacterial drugs and social pressure, the UC is increasingly prevalent in newly industrialized countries in Africa, South America and Asia, including China [1,2,3]. To assess the long-term safety and efficacy of monotherapy with a single fresh fecal microbiota transplant (FMT) for recurrent ulcerative colitis (UC)

Methods

Results

Conclusion