P717 Faecal Microbiota Transplant in Ulcerative Colitis (FMTUC) – A randomised clinical trial feasibility study
Jitsumura, M.(1,2);Cunningham , A.(1);Hitchings, M.D.(3);Wilkinson, T.(3);Kinross, J.(4);Row, P.(5);Davies, A.(6);Dean Anthony, H.(1);
(1)Singleton Hospital, Department of Colorectal Surgery, Swansea, United Kingdom;(2)Poole Hospital, General Surgery, Poole, United Kingdom;(3)Swansea University Medical School, Medical Microbiology and Infectious Diseases, Swansea, United Kingdom;(4)St. Mary's Hospital- Imperial College London, Department of Surgery and Cancer, London, United Kingdom;(5)Swansea University Medical School, Biochemistry Group, Swansea, United Kingdom;(6)Swansea University Medical School- Singleton Hospital, Public Health Wales Microbiology, Swansea, United Kingdom;
Dysbiosis of the gut microbiota may be responsible for the pathogenesis of ulcerative colitis (UC). Restoration of gut microbiota diversity by means of faecal microbiota transplantation (FMT) is of increasing interest as a therapeutic option in the management of UC. The aims of this phase II feasibility study are to estimate the magnitude of treatment response to FMT in treatment-naïve patients with newly diagnosed UC, evaluate donor and patient recruitment rates and determine optimal study conditions for phase III study (ISRCTN 58082603).
Treatment-naïve patients with histologically confirmed UC below the sigmoid were recruited. Subjects were randomised to three arms ; single FMT enema, five daily enemas and control. All groups received antibiotic for 10 days and bowel preparation 48 hours before the interventions. They were followed up for 12 weeks with quality of life (QOL) scores (IBDex, CUCQ-32) and 16S RNA study on faecal samples. Endoscopic (Mayo score) and histological assessments were performed at the baseline and week 12. The primary endpoints were endoscopic remission of UC and rate of persistent microbial engraftment at 12 weeks. Secondary endpoints included QoL and mucosal cytokine profiling with IL-10. Clinical remission was defined as Mayo score ≤ 2 with an endoscopic Mayo score of 0.
Eighteen UC patients were recruited between July 2016 and February 2020 until the COVID-19 pandemic, of those five achieved Clinical remission. One subject from the control group withdrew at week 4 due to worsening symptoms. 72% improved Mayo and QOL scores, and 44% avoided medical treatment. Clinical remission was more observed among subjects with lower baseline QoL and mild-moderate disease, although this did not reach statistical significance (P=0.173). No correlation between FMT dose, frequency and clinical remission were observed. The 16S evaluation of the faecal samples demonstrated successful engraftment of FMT and showed a similar faecal microbiota profile amongst the intervention groups, which was markedly different from the control group. Coprococcus was found to be much more abundant amongst subjects who responded to the FMT intervention. This study also suggested an inverse correlation between IL-10 and the severity of UC.
FMT intervention protocols were well adhered and achieved 94% completion rate, though the recruitment period was much longer than the original plan due to unforeseen interruptions. Yet, this feasibility study demonstrated potential for employing this method for a larger multicentre RCT to further evaluate FMT dose and frequency effects. The correlation between IL-10 and IL-10 producing microorganisms should be sought in the future study.