Data for this Review were identified by searches of MEDLINE, PubMed, Cochrane Library, and references from relevant articles using the search terms “microbiota”, “f(a)ecal transplant”, and “f(a)ecal microbiota transplantation”. Abstracts and reports from meetings were included only when they related directly to previously published work. Only articles published between Jan 1, 1950, and July 10, 2019, were included.
TherapeuticsThe evolution of the use of faecal microbiota transplantation and emerging therapeutic indications
Introduction
The understanding of the role of the microbiota in health and disease is rapidly expanding, with a major contributory factor being the increased availability of microbial genomic sequencing.1 The human gastrointestinal tract is inhabited by multiple different microorganisms, including bacteria, archaea, viruses, and fungi. Although there is no agreed definition of a healthy gut microbiota, high overall microbial diversity, stability, and redundancy of major functions have been established as key markers of a healthy state.2 Perturbations of the gut microbiota (sometimes referred to as dysbiosis) have been associated with multiple diseases; as a result, the interest in using faecal microbiota transplantation (FMT) with the aim of correcting these imbalances has increased greatly over the past decade.3 FMT is the transfer of minimally manipulated, prescreened donor stool into the gastrointestinal tract of a patient, with the aim of ameliorating the dysbiotic state by increasing overall diversity and restoring the functionality of the microbiota as well.4 We discuss the evolution of the use of FMT and emerging therapeutic indications.
Section snippets
Establishment of efficacy
Clostridioides difficile (formerly named Clostridium difficile) infection is the most common cause of infection associated with health care and remains a significant public health threat.4 C difficile infection is the condition in which gut microbiota dysbiosis has been best characterised. Antibiotic use is one of the major risk factors for C difficile infection, and antibiotic-mediated perturbation of the gut microbiota in those with this infection has been consistently described.5
C difficile
Emerging areas within C difficile infection
There are significant data to support the use of FMT in the treatment of recurrent C difficile infection; however, several other aspects of the C difficile infection landscape are now being explored, including severe and fulminant infection and the treatment of primary infections.
Nearly 8% of hospitalised patients with C difficile infection develop severe or fulminant disease.38 Due to high rates of mortality in medically refractory cases, 30% of patients with severe infection have historically
Emerging indications and areas of uncertainty
Several other indications are being explored as potential targets for FMT therapy, with variable results. We highlight a few promising indications with available trial data. As of July, 2019, more than 200 registered trials are investigating the use of FMT to treat various disorders on ClinicalTrials.gov (table 1; panel 2).
Future directions and conclusion
The emergence of randomised trials showing the marked efficacy of FMT (compared with antimicrobial therapy and placebo) in the treatment of recurrent C difficile infection has led gastroenterologists, microbiologists, infectious diseases clinicians, and other relevant stakeholders to rapidly establish FMT services globally. However, FMT clearly presents very unique and complex challenges to clinicians and regulators alike, including its poorly-defined mechanism of action, the complexities
Search strategy and selection criteria
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