Adverse events in faecal microbiota transplant: a review of the literature.

Faecal microbiota transplant (FMT) is the infusion of donor faeces into the gut with the aim of improving microbial diversity. The procedure has gained significant interest recently in the treatment of recurrent Clostridium difficile infection (CDI). The literature is currently dominated by small case series and isolated case reports. There is no standardization of methods and recording of outcomes.Submitted (immediately with CC-BY-NC-ND), or accepted after 12 month embargo (CC-BY-NC-ND

The NordICC Study: rationale and design of a randomized trial on colonoscopy screening for colorectal cancer.

To access publisher full text version of this article. Please click on the hyperlink in Additional Links field.While colonoscopy screening is widely used in several European countries and the United States, there are no randomized trials to quantify its benefits. The Nordic-European Initiative on Colorectal Cancer (NordICC) is a multinational, randomized controlled trial aiming at investigating the effect of colonoscopy screening on colorectal cancer (CRC) incidence and mortality. This paper describes the rationale and design of the NordICC trial. Men and women aged 55 to 64 years are drawn from the population registries in the participating countries and randomly assigned to either once-only colonoscopy screening with removal of all detected lesions, or no screening (standard of care in the trial regions). All individuals are followed for 15 years after inclusion using dedicated national registries. The primary end points of the trial are cumulative CRC-specific death and CRC incidence during 15 years of follow-up. POWER ANALYSIS: We hypothesize a 50 % CRC mortality-reducing efficacy of the colonoscopy intervention and predict 50 % compliance, yielding a 25 % mortality reduction among those invited to screening. For 90 % power and a two-sided alpha level of 0.05, using a 2:1 randomization, 45 600 individuals will be randomized to control, and 22 800 individuals to the colonoscopy group. Interim analyses of the effect of colonoscopy on CRC incidence and mortality will be performed at 10-year follow-up. The aim of the NordICC trial is to quantify the effectiveness of population-based colonoscopy screening. This will allow development of evidence-based guidelines for CRC screening in the general population.Nordic Cancer Union, Norway Norwegian Research Council, Norway 197309 Health Fund of South-East Norway, Norway 5135 Falk Pharma National Centre for Research and Development of Poland, Poland N R13 0024 04 Polish Foundation of Gastroenterology, Poland Dutch Ministry of Health and Health Care Prevention Program-Implementation (ZonMw), Netherland

Upper Versus Lower Gastrointestinal Delivery for Transplantation of Fecal Microbiota in Recurrent or Refractory Clostridium difficile Infection: A Collaborative Analysis of Individual Patient Data From 14 Studies.

GOALS: The aim of this study was to compare upper gastrointestinal (UGI) versus lower gastrointestinal (LGI) delivery routes of fecal microbiota transplantation (FMT) for refractory or recurrent/relapsing Clostridium difficile infection (CDI). BACKGROUND: FMT has been proven to be a safe and highly effective therapeutic option for CDI. Delivery, however, could be via the UGI or LGI routes, and it is unclear as to which route provides better clinical outcome. STUDY: A systematic search for studies that reported the use of FMT for CDI treatment was conducted. Individual patient data that included demographic (age and sex) and clinical (route of FMT delivery, CDI outcome after FMT, and follow-up time) information were obtained. Kaplan-Meier cumulative hazard curves and Cox proportional hazard models were used to assess clinical failure after FMT by the route of delivery. RESULTS: Data from 305 patients treated with FMT (208 via LGI route and 97 via UGI route) for CDI were analyzed. At 30 and 90 days, the risk of clinical failure was 5.6% and 17.9% in the UGI group compared with 4.9% and 8.5% in the LGI delivery route group, respectively. A time-varying analysis suggested a 3-fold increase in hazard of clinical failure for UGI delivery (hazard ratio, 3.43; 95% confidence interval, 1.32-8.93) in the period after 30 days. CONCLUSIONS: FMT delivered via the LGI seems to be the most effective route for the prevention of recurrence/relapse of CDI. A randomized controlled trial is necessary to confirm whether FMT delivered via the LGI is indeed superior to that delivered via the UGI route

The use of Faecal Microbiota Transplantation (FMT) in Europe : A Europe-wide survey

Publisher Copyright: © 2021 The AuthorsBackground: Faecal microbiota transplantation (FMT) is an emerging treatment modality, but its current clinical use and organisation are unknown. We aimed to describe the clinical use, conduct, and potential for FMT in Europe. Methods: We invited all hospital-based FMT centres within the European Council member states to answer a web-based questionnaire covering their clinical activities, organisation, and regulation of FMT in 2019. Responders were identified from trials registered at clinicaltrials.gov and from the United European Gastroenterology (UEG) working group for stool banking and FMT. Findings: In 2019, 31 FMT centres from 17 countries reported a total of 1,874 (median 25, quartile 10–64) FMT procedures; 1,077 (57%) with Clostridioides difficile infection (CDI) as indication, 791 (42%) with experimental indications, and 6 (0•3%) unaccounted for. Adjusted to population size, 0•257 per 100,000 population received FMT for CDI and 0•189 per 100,000 population for experimental indications. With estimated 12,400 (6,100–28,500) annual cases of multiple, recurrent CDI and indication for FMT in Europe, the current European FMT activity covers approximately 10% of the patients with indication. The participating centres demonstrated high safety standards and adherence to international consensus guidelines. Formal or informal regulation from health authorities was present at 21 (68%) centres. Interpretation: FMT is a widespread routine treatment for multiple, recurrent CDI and an experimental treatment. Embedded within hospital settings, FMT centres operate with high standards across Europe to provide safe FMT. A significant gap in FMT coverage suggests the need to raise clinical awareness and increase the FMT activity in Europe by at least 10-fold to meet the true, indicated need. Funding: NordForsk under the Nordic Council and Innovation Fund Denmark (j.no. 8056–00006B).Peer reviewe

Sinus Microbiome Diversity Depletion and Corynebacterium tuberculostearicum Enrichment Mediates Rhinosinusitis

Persistent mucosal inflammation and microbial infection are characteristics of chronic rhinosinusitis (CRS). Mucosal microbiota dysbiosis is found in other chronic inflammatory diseases; however, the relationship between sinus microbiota composition and CRS is unknown. Using comparative microbiome profiling of a cohort of CRS patients and healthy subjects, we demonstrate that the sinus microbiota of CRS patients exhibits significantly reduced bacterial diversity compared with that of healthy controls. In our cohort of CRS patients, multiple, phylogenetically distinct lactic acid bacteria were depleted concomitant with an increase in the relative abundance of a single species, Corynebacterium tuberculostearicum. We recapitulated the conditions observed in our human cohort in a murine model and confirmed the pathogenic potential of C. tuberculostearicum and the critical necessity for a replete mucosal microbiota to protect against this species. Moreover, Lactobacillus sakei, which was identified from our comparative microbiome analyses as a potentially protective species, defended against C. tuberculostearicum sinus infection, even in the context of a depleted sinus bacterial community. These studies demonstrate that sinus mucosal health is highly dependent on the composition of the resident microbiota as well as identify both a new sino-pathogen and a strong bacterial candidate for therapeutic intervention