Faecal Microbiota Transplantation Engraftment After Budesonide or Placebo in Patients With Active Ulcerative Colitis Using Pre-selected Donors:A Randomized Pilot Study

Background: Faecal microbiota transplantation [FMT] shows some efficacy in treating patients with ulcerative colitis [UC], although variability has been observed among donors and treatment regimens. We investigated the effect of FMT using rationally selected donors after pretreatment with budesonide or placebo in active UC. Methods: Patients ≥18 years old with mild to moderate active UC were randomly assigned to 3 weeks of budesonide [9 mg] or placebo followed by 4-weekly infusions of a donor faeces suspension. Two donors were selected based on microbiota composition, regulatory T cell induction and short-chain fatty acid production in mice. The primary endpoint was engraftment of donor microbiota after FMT. In addition, clinical efficacy was assessed. Results: In total, 24 patients were enrolled. Pretreatment with budesonide did not increase donor microbiota engraftment [p = 0.56] nor clinical response, and engraftment was not associated with clinical response. At week 14, 10/24 [42%] patients achieved [partial] remission. Remarkably, patients treated with FMT suspensions from one donor were associated with clinical response [80% of responders, p &lt; 0.05] but had lower overall engraftment of donor microbiota. Furthermore, differences in the taxonomic composition of the donors and the engraftment of certain taxa were associated with clinical response. Conclusion: In this small study, pretreatment with budesonide did not significantly influence engraftment or clinical response after FMT. However, clinical response appeared to be donor-dependent. Response to FMT may be related to transfer of specific strains instead of overall engraftment, demonstrating the need to characterize mechanisms of actions of strains that maximize therapeutic benefit in UC.</p

Human transmission of blastocystis by fecal microbiota transplantation without development of gastrointestinal symptoms in recipients

Background. Patients with multiple recurrent Clostridioides difficile infections (rCDI) are treated with fecal microbiota transplantation (FMT), using feces provided by healthy donors. Blastocystis colonization of donors is considered an exclusion criterion, whereas its pathogenicity is still under debate. Methods. The introduction of molecular screening for Blastocystis sp. at our stool bank identified 2 donors with prior negative microscopies but positive polymerase chain reactions (PCRs). Potential transmission of Blastocystis sp. to patients was assessed on 16 fecal patient samples, pre- and post-FMT, by PCR and subtype (ST) analyses. In addition, clinical outcomes for the treatment of rCDI (n = 31), as well as the development of gastrointestinal symptoms, were assessed. Results. There was 1 donor who carried Blastocystis ST1, and the other contained ST3. All patients tested negative for Blastocystis prior to FMT. With a median diagnosis at 20.5 days after FMT, 8 of 16 (50%) patients developed intestinal colonization with Blastocystis, with identical ST sequences as their respective donors. Blastocystis-containing fecal suspensions were used to treat 31 rCDI patients, with an FMT success rate of 84%. This success rate was not statistically different from patients transferred with Blastocystis sp.–negative donor feces (93%, 76/82). Patients transferred with Blastocystis sp.–positive donor feces did not report any significant differences in bowel complaints in the first week, after 3 weeks, or

How to prepare stool banks for an appropriate response to the ongoing COVID-19 pandemic: Experiences in the Netherlands and a retrospective comparative cohort study for faecal microbiota transplantation.

BACKGROUND: Faecal microbiota transplantation (FMT) is an efficacious treatment for patients with recurrent Clostridioides difficile infections (rCDI). Stool banks facilitate FMT by providing screened faecal suspensions from highly selected healthy donors. Due to the ongoing coronavirus disease 2019 (COVID-19) pandemic and the potential risk of SARS coronavirus-2 (SARS-CoV-2) transmission via FMT, many stool banks were forced to temporarily halt and adjust donor activities. GOAL: The evaluation of a strategy to effectively continue stool banking activities during the ongoing COVID-19 pandemic. STUDY: To restart our stool banking activities after an initial halt, we implemented periodic SARS-CoV-2 screening in donor faeces and serum, and frequent donor assessment for COVID-19 related symptoms. FMT donor and recipient data obtained before (2016–2019) and during the COVID-19 pandemic (March 2020-August 2021) were compared to assess stool banking efficacy. RESULTS: Two out of ten donors developed COVID-19. No differences during versus before the COVID-19 pandemic were observed in the number of approved faeces donations (14 vs 22/month, p = 0.06), FMT requests for rCDI (3.9 vs 4.3/month, p = 0.6); rCDI patients eligible for FMT (80.6% vs 73.3%, p = 0.2); rCDI cure rate (90.3% vs 89.2%, p = 0.9); CDI-free survival (p = 0.7); the number of non-rCDI patients treated with FMT (0.5/month vs 0.4/month), and the number of possibly FMT related adverse events (9.5% vs 7.8%, p = 0.7). Two FMTs for rCDI were delayed due to COVID-19. CONCLUSIONS: There is a continued need for FMT treatment of rCDI during the COVID-19 pandemic. Appropriate donor screening and SARS-CoV-2 infection prevention measures can be implemented in existing protocols without increasing the burden for donors, and allow safe, effective and efficient FMT during the ongoing COVID-19 pandemic. Stool banks should evaluate their SARS-CoV-2 donor screening protocols for long-term sustainability and efficacy, and share their experiences to help the utilisation, standardisation and improvement of stool banks worldwide

Faecal microbiota transplantation for Clostridioides difficile infection: Four years’ experience of the Netherlands Donor Feces Bank

Background: The Netherlands Donor Feces Bank provides standardized ready-to-use donor faecal suspensions for faecal microbiota transplantation treatment of patients with recurrent Clostridioides difficile infection. Objective: The purpose of this study was evaluation of safety, feasibility and outcome of faecal microbiota transplantation facilitated by a national stool bank. Methods: The methods used included: observational cohort study of donors and recipients of faecal suspensions; assessment of donor screening and patient selection performed by an expert panel of medical microbiologists, gastroenterologists and infectious disease specialists; and patient outcome evaluated at different timepoints after faecal microbiota transplantation. Results: Of 871 volunteers who registered as a potential faeces donor, 16 (2%) became active donors. Nine donors stopped or were excluded after a mean donation period of 5.7 months. In 2016–2019, 47 (27%) of 176 requests for faecal microbiota transplantations were deemed not indicated by the expert panel. In total, 129 patients with recurrent C. difficile infection were treated with 143 faecal suspensions in 40 different hospitals. The cure rate at two months after a single infusion was 89% (107/120). Of 84 patients, long-term follow-up (median 42 weeks) was available and sustained cure was achieved in 61 (73%). Early C. difficile infection relapses (within two months after faecal microbiota transplantation) and late recurrences (after more than two months) occurred more frequently in patients who received non-C. difficile antibiotics within three weeks after faecal microbiota transplantation and in moderately to severely immunocompromised patients. Of 21 patients with C. difficile infection after faecal microbiota transplantation, 14 were cured with anti-C. difficile antibiotics and seven with a second transplantation. No faecal microbiota transplantation-related serious adverse events were observed, but gastro-intestinal complaints (nausea, abdominal pain or diarrhoea) persisted in 32% of the treated patients at long-term follow-up. Conclusion: Faecal suspensions provided by a centralized stool bank, supported by a multidisciplinary expert team, resulted in effective, appropriate and safe application of faecal microbiota transplantation for recurrent C. difficile infection. Level of evidence: Level II, prospective cohort study