Faecal microbiota transplantation – getting your dysbiosis index right
Magdy El-Salhy, Professor of Gastroenterology and Hepatology at the University of Bergen
The gastroenterology community is getting more and more excited about the therapeutic potential of faecal microbiota transplantation (FMT) for a number of conditions, including irritable bowel syndrome (IBS). Surprisingly, however, lots of FMT studies haven’t reported a consistent set of patient responses. Magdy El-Salhy, Professor of Gastroenterology and Hepatology at the University of Bergen, followed his gut in a bid to solve this. He wanted to confirm his suspicions that greater standardisation of various aspects of the trial protocol design is required, including donor selection criteria, in order to establish ‘super-donors’ and ensure positive outcomes for recipient patients. Magdy and his research team designed a study that tested this hypothesis by performing microbial profiling of both FMT donors and recipients, using the GA-map® Dysbiosis Test (GA-map® Test) with great success.1
What is FMT, and how can it help IBS patients?
FMT is just what it sounds like. Basically, it’s a stool transplant – transferring faecal microbes from a healthy donor into the gut of a recipient – to improve a medical condition, particularly those that involve ‘dysbiosis’, an imbalance in the gut microbiome. The development of IBS has been linked to microbiome disturbances and, more recently, clinicians and researchers have started to characterise IBS by the level of dysbiosis. The theory is that infusing a patient’s gut with a healthy faecal sample can improve their intestinal flora, helping to alleviate the symptoms of IBS.
The dirty on dysbiosis tests
Dysbiosis tests are a great way to measure the make-up and diversity of a patient’s gut microbiome. The GA-map® Test – a gut microbiota DNA-based platform that identifies and characterises dysbiosis – was used throughout the FMT trial conducted by Professor El-Salhy and his team. A key aspect of this test is that it assigns samples a ‘dysbiosis index’ that qualifies the degree of microbiome disturbance compared to a healthy population, as well as giving an idea of the abundance of species present. This makes it a clinician’s perfect tool for making complex microbial profiling of both patients and donors in FMT trials fast and simple, providing standardised results that can be analysed on site to see how well the treatment is going.
What did the study involve?
It was a randomised, double-blind placebo-controlled study that involved 165 patients with IBS. Patients were either given placebo – their own faeces – or varying doses of FMT. Professor El-Salhy carefully designed the protocol with five key factors: donors were screened against set criteria; the faecal samples from the donor were frequently analysed to monitor the stability of their microbiome; the fresh donor faeces were immediately frozen; samples were manually mixed before being administered; and the transplant was administered by gastroscope directly into the recipient’s duodenum. A ‘response’ to treatment was recorded if a patient experienced a reduction – at least a 50-point decrease in total score – in IBS symptoms at three months.
What were its findings?
The study found that FMT is an effective therapy for IBS, with up to 89.1 % of patients responding to treatment, and around half of all patients experiencing clinical improvements in abdominal symptoms, fatigue and quality of life. Microbial profiling of the patients who received FMT doses revealed that their intestinal flora also significantly changed. Magdy’s trial confirmed that protocol design is crucial for success in FMT studies, and highlighted the importance of standardisation through characterising donor and recipient gut microbiota using validated dysbiosis tests.
What next?
Dysbiosis is not a well-defined term, and further use of testing platforms that assign indexes – like that from the GA-map® Test – can lead to greater understanding of the pathophysiology of gastrointestinal disorders. Not only this, but better patient outcomes can also be ensured by more finely tuning the FMT therapy procedure, including the potential of future donor-recipient matching. Other chronic conditions that are also associated with microbial dysbiosis – such as metabolic syndrome, obesity and even Parkinson’s disease – also stand a chance of benefitting from making FMT more successful.
References
- El-Salhy M, Gunnar Hatlebakk J, Kristoffersen AB, Hausken T. Gut microbiota Efficacy of faecal microbiota transplantation for patients with irritable bowel syndrome in a randomised, double-blind, placebo-controlled study. Gut. 2020;69:859-867. doi:10.1136/gutjnl-2019-319630
