The use of faecal microbiota transplant as treatment for recurrent or refractory Clostridioides difficile infection and other potential indications: second edition of joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines.

The first British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS)-endorsed faecal microbiota transplant (FMT) guidelines were published in 2018. Over the past 5 years, there has been considerable growth in the evidence base (including publication of outcomes from large national FMT registries), necessitating an updated critical review of the literature and a second edition of the BSG/HIS FMT guidelines. These have been produced in accordance with National Institute for Health and Care Excellence-accredited methodology, thus have particular relevance for UK-based clinicians, but are intended to be of pertinence internationally. This second edition of the guidelines have been divided into recommendations, good practice points and recommendations against certain practices. With respect to FMT for Clostridioides difficile infection (CDI), key focus areas centred around timing of administration, increasing clinical experience of encapsulated FMT preparations and optimising donor screening. The latter topic is of particular relevance given the COVID-19 pandemic, and cases of patient morbidity and mortality resulting from FMT-related pathogen transmission. The guidelines also considered emergent literature on the use of FMT in non-CDI settings (including both gastrointestinal and non-gastrointestinal indications), reviewing relevant randomised controlled trials. Recommendations are provided regarding special areas (including compassionate FMT use), and considerations regarding the evolving landscape of FMT and microbiome therapeutics.

Results from the first English stool bank using faecal microbiota transplant as a medicinal product for the treatment of Clostridioides difficile infection.

BACKGROUND: Faecal Microbiota Transplant (FMT) has improved outcomes for the treatment of Clostridioides difficile infection (CDI) compared to antibiotic therapy. FMT is classified as a medicinal product in the United Kingdom, similar to the USA and Canada, limiting supply via stool banks without appropriate licencing. In the largest UK cohort to date, we describe the clinical outcomes for 124 patients receiving FMT for recurrent or refractory CDI and present a framework to produce FMT as a licenced medicinal product. METHODS: Anonymous unrelated healthy donors, screened via health assessment and microbiological testing donated stool. In aerobic conditions FMT aliquots were prepared for immediate use or frozen storage, following a production framework developed to comply with Good Manufacturing Practice. Outcome measures were clinical response to FMT defined as resolution of diarrhoea within seven days and clinical cure defined as response without diarrhoea recurrence at 90 days. FINDINGS: Clinical response was 83·9% (95% CI 76·0%-90·0%) after one treatment. Clinical cure was 78·2% (95% CI 67·4%-89·0%) across the cohort. Refractory cases appeared to have a lower initial clinical response rate compared to recurrent cases, however at day 90 there were no differences observed between these groups. INTERPRETATION: The methodology developed here enabled successful licencing of FMT by The Medicines and Healthcare products Regulatory Agency as a medicinal product. This has widened the availability of FMT in the National Health Service via a stool bank and can be applied in other centres across the world to improve access to safe and quality assured treatments.

Immunological mechanisms underpinning faecal microbiota transplantation for the treatment of inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a chronic gastrointestinal disease that results from a dysregulated immune response against specific environmental triggers in a genetically predisposed individual. Increasing evidence has indicated a causal role for changes in gut microbiota (dysbiosis) contributing to this immune-mediated intestinal inflammation. These mechanisms involve dysregulation of multiple facets of the host immune pathways that are potentially reversible. Faecal microbiota transplantation (FMT) is the transfer of processed stool from a healthy donor into an individual with an illness. FMT has shown promising results in both animal model experiments and clinical studies in IBD in the resolution of intestinal inflammation. The underlying mechanisms, however, are unclear. Insights from these studies have shown interactions between modulation of dysbiosis via changes in abundances of specific members of the gut microbial community and changes in host immunological pathways. Unravelling these causal relationships has promising potential for a translational therapy role to develop targeted microbial therapies and understand the mechanisms that underpin IBD aetiopathogenesis. In this review, we discuss current evidence for the contribution of gut microbiota in the disruption of intestinal immune homeostasis and immunoregulatory mechanisms that are associated with the resolution of inflammation through FMT in IBD.

Faecal transplantation for IBD management-pitfalls and promises.

BACKGROUND: Faecal microbiota transplantation (FMT) as a potential treatment for inflammatory bowel disease (IBD) is an area of active current research, having been stimulated by the remarkable efficacy of FMT in treatment of Clostridium difficile-associated colitis. SOURCES OF DATA: This review is based on data from numerous case series on FMT in IBD since 1989 and results of four RCTs in ulcerative colitis (UC); three fully published. AREAS OF AGREEMENT: Early signals of short to medium-term efficacy of FMT for UC are promising. AREAS OF CONTROVERSY: Methodology, underlying mechanisms and questions regarding safety of FMT remain controversial. GROWING POINTS: Many trials of FMT in adults and children are currently recruiting. AREAS TIMELY FOR DEVELOPING RESEARCH: Future trials of FMT will likely revisit Crohn's disease and patients undergoing pouch surgery. Advances in microbial culture complementing genetic sequencing and investigations into the virome and mycobiome in IBD will be of great future interest.

Systematic review with meta-analysis: the efficacy of faecal microbiota transplantation for the treatment of recurrent and refractory Clostridium difficile infection.

BACKGROUND: Clostridium difficile infection (CDI) is the commonest nosocomial cause of diarrhoea. Faecal microbiota transplantation (FMT) is an approved treatment for recurrent or refractory CDI but there is uncertainty about its use. AIM: To evaluate the efficacy of FMT in treating recurrent and refractory CDI and investigate outcomes from modes of delivery and preparation. METHODS: A systematic review and meta-analysis was performed. MEDLINE, EMBASE, CINAHL, Cochrane Library, trial registers and conference proceedings were searched. Studies on FMT in recurrent and refractory CDI were included. The primary outcome was clinical resolution with subgroup analyses of modes of delivery and preparation. Random effects meta-analyses were used to combine data. RESULTS: Thirty seven studies were included; seven randomised controlled trials and 30 case series. FMT was more effective than vancomycin (RR: 0.23 95%CI 0.07-0.80) in resolving recurrent and refractory CDI. Clinical resolution across all studies was 92% (95%CI 89%-94%). A significant difference was observed between lower GI and upper GI delivery of FMT 95% (95%CI 92%-97%) vs 88% (95%CI 82%-94%) respectively (P=.02). There was no difference between fresh and frozen FMT 92% (95%CI 89%-95%) vs 93% (95%CI 87%-97%) respectively (P=.84). Administering consecutive courses of FMT following failure of first FMT resulted in an incremental effect. Donor screening was consistent but variability existed in recipient preparation and volume of FMT. Serious adverse events were uncommon. CONCLUSION: Faecal microbiota transplantation is an effective treatment for recurrent and refractory Clostridium difficile infection, independent of preparation and route of delivery.

Evaluation of gut bacterial populations using an electronic e-nose and field asymmetric ion mobility spectrometry: further insights into 'fermentonomics'.

The fermentation of undigested foods in the large bowel, by its resident bacteria, results in the production of several chemicals including volatile gases. Perturbance in gut bacteria is known to influence colonic and metabolic health, but to determine this requires prolonged culture (often unsuccessful) or expensive genomic sequencing. Clearly this is not practical for daily clinical practice. Previously, we have reported our insights into fermentonomics through the detection of volatile organic compounds (VOCs) in patients with gastrointestinal and metabolic diseases, using the electronic nose. In this paper we report on the changes in the fermentone produced by patients undergoing complete versus partial bowel cleansing. Using urine samples, preliminary results from 23 individuals receiving bowel cleansing indicate the ability of the electronic nose to distinguish between the partial and complete procedures. Moreover in a subset of individuals, we have been able to track evolving bacterial recolonization over time using the e-nose and field asymmetric ion mobility spectrometry (FAIMS). Such an approach has practical application in tracking bacterial dysbiosis following perturbation.