Single Delivery of High-Diversity Fecal Microbiota Preparation by Colonoscopy Is Safe and Effective in Increasing Microbial Diversity in Active Ulcerative Colitis

Abstract

Background: Recent trials suggest fecal microbiota transplantation (FMT) with repeated enemas and high diversity FMT donors is a promising treatment to induce remission in ulcerative colitis (UC). Methods: We designed a prospective, open-label pilot study to assess the safety, clinical efficacy, and microbial engraftment of single FMT delivery by colonoscopy for active UC using a two donor fecal microbiota preparation (FMP). Safety and clinical endpoints of response, remission, and mucosal healing at week 4 were assessed. Fecal DNA and rectal biopsies were used to characterize the microbiome and mucosal CD4+ T cells, respectively, before and after FMT. Results: Seven patients (35%) achieved a clinical response by week 4. Three patients (15%) were in remission at week 4 and two of these patients (10%) achieved mucosal healing. Three patients (15%) required escalation of care. No serious adverse events were observed. Microbiome analysis revealed that restricted diversity of recipients pre-FMT was significantly increased by high diversity two donor FMP. The microbiome of recipients post-transplant was more similar to the donor FMP than the pre-transplant recipient sample in both responders and non-responders. Notably, donor composition correlated with clinical response. Mucosal CD4+ T cell analysis revealed a reduction in both Th1 and regulatory T cells post-FMT. Conclusions: High-diversity, two donor FMP delivery by colonoscopy is safe and effective in increasing fecal microbial diversity in patients with active UC. Donor composition correlated with clinical response and further characterization of immunological parameters may provide insight into factors influencing clinical outcome.

Combined Endoscopic and Oral Fecal Microbiota Transplantation in Patients with Antibiotic-Dependent Pouchitis: Low Clinical Efficacy due to Low Donor Microbial Engraftment

“…Despite the small sample size, the results suggest that donor FMT engraftment in this patient group is surprisingly low despite a combined endoscopic and oral high-intensity FMT approach, which is considered one of the factors of success for FMT in patients with UC [14]. In contrast, engraftment of FMT in patients with a preserved colon in FMT trials for recurrent C. difficile infection and UC is at least 80% [15, 16]. Also, as shown in patients with UC undergoing FMT, the microbiome of recipients after transplant is more similar to the donor FMP than the pretransplant recipient sample engraftment, suggesting that FMT engraftment is a prerequisite for therapeutic success [16].…”

“…In contrast, engraftment of FMT in patients with a preserved colon in FMT trials for recurrent C. difficile infection and UC is at least 80% [15, 16]. Also, as shown in patients with UC undergoing FMT, the microbiome of recipients after transplant is more similar to the donor FMP than the pretransplant recipient sample engraftment, suggesting that FMT engraftment is a prerequisite for therapeutic success [16]. The reason for the low engraftment in our study could be due to several factors, including donor selection, the dose and frequency of FMT, and the pouch microenvironment.…”

Gut microbiota in ulcerative colitis: insights on pathogenesis and treatment

“…However, over time, the abundance of flora from the same donor varies significantly and, therefore, extensive microflora provided by multiple donors could effectively treat recurrent UC. Another study reported that, in patients with active UC, the high diversity of two‐donor FMT administered through a colonoscopy appears to be a safe and effective strategy for increasing fecal microbial diversity with an aim of clinical remission …”

Fecal microbiota transplantation for hepatic encephalopathy: Ready for prime time?

“…The concept that donor stool characteristics may influence FMT efficacy has been recognized in inflammatory bowel disease . Bajaj et al carried forward this novel concept by utilizing donor stool enriched with microbial taxa found to be beneficial in cross‐sectional HE studies .…”

“…The concept that donor stool characteristics may influence FMT efficacy has been recognized in inflammatory bowel disease. (8) Bajaj et al carried forward this novel concept by utilizing donor stool enriched with microbial taxa found to be beneficial in cross-sectional HE studies. (2) Although an excellent starting point for targeted donor selection, this "one-size-fits-all" approach to donor selection will likely benefit from further refinement given that: (1) not all patients with the same disease have similar microbial profiles (9) and (2) our current understanding of "beneficial" taxa from cross-sectional HE studies is based on association rather than causation.…”