Ep.02 – Dr Benjamin Mullish
Episode two of Inside Matters.
FMT, Donor Selection, and the Microbiome in Immuno-oncology.
Our guest on episode 2 is Dr Benjamin Mullish. Dr Mullish is an NIHR Academic Clinical Lecturer in the Department of Metabolism, Digestion and Reproduction at Imperial College London and an Honorary Specialty Registrar in Gastroenterology and Hepatology at St Mary's Hospital, Imperial College Healthcare NHS Trust.
We discuss all things FMT / IMT, microbial therapeutics and how to unlock the therapeutic potential of the gut microbiome in diseases such as cancer.
Key takeaways from this episode:
Intestinal microbiota transfer (IMT, also referred to as faecal microbiota transplantation) is a medical procedure in which microorganisms are moved from a healthy donor (or donors) into the intestinal tract of a recipient.
The first randomised controlled trial of IMT was published in the New England Journal of Medicine in 2013 (https://www.nejm.org/doi/full/10.1056/nejmoa1205037). This study showed for the first time that FMT was an effective treatment. Dr Mullish described that this publication transformed the field and catalysed a wave of interest and research into IMT.
IMT has evolved over the last decade, with advancements made to donor selection and screening, material processing and patient preparation, as well as guidelines providing guidance to clinicians. Dr Mullish was lead co-author on the joint UK/BSG consensus guideline publication describing best practice and the evidence base for IMT (https://www.bsg.org.uk/wp-content/uploads/2018/09/The-use-of-faecal-microbiota-transplant-as-treatment-for-recurrent-or-refractory-Clostridium-difficile-infection-and-other-potential-indications-1.pdf)
There are risks associated with IMT, mainly relating to pathogen screening. There have been recorded deaths in the literature associated with the transfer of pathogens (https://www.nejm.org/doi/full/10.1056/NEJMoa1910437). These deaths emphasise the importance of robust and stringent donor selection, donor screening and controls relating to testing and manufacture. All of which are outlined in consensus guidelines.
Dr Mullish is currently updating the guidance. Over the course of the revision process, he and the team have identified 20,000 publications that relate to FMT/IMT published since 2018. Of that 20,000 - 11,000 do not relate to C.difficile and 8,000 relate to C.difficile publicationsDr Mullish and James discussed what makes a good donor. In short - it’s complicated. Fundamentally a good donor is one what is free from disease and that produces high quality stool on a regular basis. Dr Mullish describes new studies and techniques that focus on analysing the chemical outputs of the microbiome - known the metabolome. The metabolome differs between healthy people and controls, as well as before and after IMT. Dr Mullish also describes bile acids as being substances produced by the body that are then modulated by the microbiome.
On the metabolome, it is accepted that there is more data than we can / know how to interpret.
It may be that in the future donors for IMT may be asked to consume a particular diet to enhance the quality of their donations.Dr Mullish describes the microbiome as being ‘co-evolved’ with our bodies and the microbiome living in symbiosis with us as hosts. We nourish them through food that we can’t digest and in return, they produce chemicals that benefit our health, such as short chain fatty acids, are energy sources for the inner aspect of the intestine.
There is emerging research linking the microbiome and IMT to outcomes in immuno-oncology (https://pubmed.ncbi.nlm.nih.gov/33303685/) and cancer (https://www.science.org/doi/10.1126/science.abc4552). Dr Mullish and the team at Imperial College London are actively involved in research into these areas.
Both James and Dr Mullish are hopeful and excited about the future of microbiome therapeutics.