April 28, 2017
Fecal microbiota transplant shows promise in patients with active ulcerative colitis, according to a new pilot study funded by the Center for Advanced Digestive Care and co-led by Drs. Carl Crawford, Randy Longman, and Vinita Jacob, all faculty of the Division of Gastroenterology and Hepatology at Weill Cornell Medicine.
First used in 4th century China, with modern application starting as early as 1958, interest in fecal microbiota transplantation (FMT) has risen greatly in the past decade as understanding of the role of the gut microbiota has evolved and expanded. FMT has been proposed to treat a range of diseases, including persistent C. difficile and H. pylori infections, irritable bowel syndrome, post-weaning diarrhea, celiac disease, and inflammatory bowel disease. Numerous small, one-armed cohort studies from various centers nationwide have contributed to the body of work regarding FMT in ulcerative colitis, showing moderate but varying success.
Weill Cornell researchers performed an open-label, pilot study of twenty patients with active ulcerative colitis (UC) underwent fecal transplant. Both the delivery and its contents were unique when compared to other FMT studies.
- The team delivered a single 120 mL fecal preparation by colonoscopy, rather than multiple deliveries.
- The preparation contained two-donor concentrate sourced from Openbiome. Two-donor preparation was intended to enhance the biodiversity of the preparation, based on observations made about previous studies.
“Research done by others did not show a robust effect on FMT in patients with UC as a group,” said Dr. Carl Crawford. “However, there were a handful of patients who did better than expected out of the group. We felt that this may have been secondary to the batch to batch variation of the donor samples. To enhance the biodiversity in our patients we pooled donor samples from two individuals to be used in our study to theoretically make up for communities of bacteria that may not have been present in the other donor.“
Dr. Crawford and his fellow researchers think combining samples from donors in the future may allow us to increase biodiversity in patients and standardize transplant solutions across multiple recipients. Once the contents of an FMT delivery can be standardized through multi-donor combinations, outcomes can be better studied on a biochemical level.
The study selected patients with active ulcerative colitis, using Mayo Scores ≥ 3 and endoscopic subscore ≥ 1. For the purposes of the study, UC patients with a C. difficile infection as well as other conventional GI pathogens were not included in the study population. Patients were also allowed to continue on their conventional medications during the study.
Microbial diversity in subjects was tracked with stool samples analyzed by the Longman lab at 2 and 4-week intervals after FMT application. Patients also underwent colonoscopy at week 4 to measure change in Mayo score and bleeding scores. The primary outcome was defined as clinical response at week 4, defined by reduction in Mayo score and bleeding subscores. Secondary outcomes included remission of UC (Mayo score ≤ 2 and no subscore > 1) and mucosal healing (endoscopy subscore of 0)
Outcomes in the 20 patients showed promise, with no serious adverse events:
- Seven of twenty patients (35%) achieved the primary goal, with three in remission by week 4 (15%) and two achieving mucosal healing (10%)
- Three of twenty patients (15%) required escalation of care, two of which were put on anti-TNFs and one undergoing colectomy.
- 16S rRNA analysis showed donor microbial diversity greatly increased, and composition more greatly reflected the donors’ microbial composition than recipients’ initial composition as soon as week 2.
The lead researchers note that while the endpoints for this pilot vary from other recent studies, the outcomes are promising. They note that results seen in this study are comparable to those seen in a recent randomized control trial, suggesting a potential favorable role for FMT in patients with ulcerative colitis. The comparable success of this open label pilot suggests the methods used for creating the preparation and the single delivery are safe and effective to achieve desired outcomes.
Dr. Longman sees a need for ongoing follow-up and analysis of microbial diversity in these patients in for long-term outcomes reporting. He also notes the study’s unique FMT preparation adds a critical piece of evidence to the body of work surrounding FMT.
“Our preliminary microbial analysis suggest that donor composition is important,” notes Dr. Longman. “Further work in the lab will evaluate the critical components of the microbiome that interact with the immune system to promote mucosal healing.”
The data from this preliminary study will be used to determine targeted protocols for a larger, randomized trial in the near future. A full publication analyzing this of this pilot study is due in 2017.