Abstract
Faecal microbiota transplantation (FMT) is the transfer of screened and minimally processed faecal material from a ‘healthy’ donor to ‘diseased’ recipient. It has an established role, and is recommended as a therapeutic strategy, in the management of recurrent Clostridioides difficile infection (CDI). Recognition that gut dysbiosis is associated with, and may contribute to, numerous disease states has led to interest in exploiting FMT to ‘correct’ this microbial imbalance. Conditions for which it is proposed to be beneficial include inflammatory bowel disease, irritable bowel syndrome, liver disease and hepatic encephalopathy, neuropsychiatric conditions such as depression and anxiety, systemic inflammatory states like sepsis, and even coronavirus disease 2019. To understand what role, if any, FMT may play in the management of these conditions, it is important to consider the potential risks and benefits of the therapy. Regardless, there are several barriers to its more widespread adoption, which include incompletely understood mechanism of action (especially outside of CDI), inability to standardise treatment, disagreement on its active ingredients and how it should be regulated, and lack of long-term outcome and safety data. Whilst the transfer of faecal material from one individual to another to treat ailments or improve health has a history dating back thousands of years, there are fewer than 10 randomised controlled trials supporting its use. Moving forward, it will be imperative to gather as much data from FMT donors and recipients over as long a timeframe as possible, and for trials to be conducted with rigorous methodology, including appropriate control groups, in order to best understand the utility of FMT for indications beyond CDI. This review discusses the history of FMT, its appreciable mechanisms of action with reference to CDI, indications for FMT with an emerging evidence base above and beyond CDI, and future perspectives on the field.
Highlights
A brief history of faecal microbiota transplantation The first documented use of the ingestion of faecal material to treat illness comes from the Sanskrit text Charak Samhita
Concurrent inflammatory bowel disease (IBD) is common (80% patients), the dysbiosis seen is distinct even from that seen in patients with IBD alone.[56]
Data are starting to emerge to suggest Faecal microbiota transplantation (FMT) may have a role to play in the management of alcoholic hepatitis (AH), with a couple of small studies showing reduction in mortality (80% survival in intervention groups versus 30– 40% in control groups) and disease-associated complications, including ascites and hepatic encephalopathy, up to 1 year of follow up.[85,86]
Summary
Severe (primary) CDI Traditional management of severe CDI refractory to antibiotics has been colectomy. Concurrent IBD is common (80% patients), the dysbiosis seen is distinct even from that seen in patients with IBD alone.[56] It is proposed that bacterial translocation across an inflamed gut drives an inflammatory process in the biliary tree, leading to disease This theory is supported in animal models.[57] Attempts to modulate the gut microbiota of patients with PSC has been trialled with antimicrobials with mixed results, and it is not currently recommended as a therapeutic strategy.[58,59] An open-label pilot study published last year demonstrated biochemical improvement (alkaline phosphatase levels fell by 50%) in recipients (3/10) of FMT in which there was donor engraftment out to 6 months post-transplant.[60] The slowly progressive nature of disease means that long-term follow up will be necessary in future trials to establish any effect of FMT on patient outcomes. The study did not include a control group and there was a per-protocol analysis;[129] results are encouraging, and RCTs are warranted to investigate further
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