Episode 002 - Dr Benjamin Mullish - FMT, donor selection, and the microbiome in immuno-oncology

Episode 002 - Dr Benjamin Mullish - faecal microbiota transplantation, donor selection, the microbiome in immuno-oncology.

Dr Mullish discusses the microbiome, the evolution of faecal microbiota transplantation (‘FMT’ also known as intestinal microbiota transfer ‘IMT’) including donor selection, novel microbial therapies, developing consensus guidelines for the benefit of patients and his involvement in exciting cutting-edge research into immuno-oncology.

Dr Mullish is a pioneer in the application of IMT to treat and prevent disease. He is the co-first author on the joint UK BSG/HIS consensus guideline guidance that defined best practices in all aspects of an IMT service. Dr Mullish has also published research that outlines the mechanism of action of IMT in recurrent C.difficile infection and is actively involved in several other research studies, trials and projects.

00:00 Intro

03:21 How Did Dr Mullish Get Started with FMT?

07:15 What Happened Next?

09:45 Were you convinced that FMT was going to be big?

10:30 When Was the First Time Dr Mullish Saw FMT With His Own Eyes?

13:43 Further Exploring the journey into FMT and its Expansion

16:34 In the Early Days What Guidance was there For Doing FMT Correct

20:01 What Evidence Suggested that Frozen Samples Were Just as Good as Fresh Samples?

22:25 Are We Still of the View that Frozen and Fresh are as Good as Each Other?

23:52 Is it Fair to Say that there was no Guidance From Formal Agencies on FMT in the Beginning?

25:59 How Did You Make Sure all Key Elements were Contained Within Guideline Documents Sent Out to Interested Parties?

27:30 Within the Document Which Areas Were Contentious?

29:00 Should Hospitals Always Maintain an FMT Practice?

31:26 Revisiting FMT Guidelines in 2012 in Regards to Today

32:42 Conversation on Do-It-Yourself FMT

34:52 Do We Have Somewhere for DIY People to go for FMT?

37:03 Discovering Better Ways for FMT

39:31 Conversation on Donor Screening

46:48 Interesting and Cool Aneqdotes / Observations

47:54 What Makes a Good Donor?

50:09 FMT and Weightloss

53:05 What is a Metabalone and Picking Donors Based on Metabalones

54:43 Non-Digestible Components and How they Affect Bugs Which Affect Us

56:35 Selecting a Donor Based on Short Chain Fatty Acids

57:55 Should We be Asking Donors to Eat Specific Foods?

59:37 Is There a Shift Towards a Particular Type of Donor? And are there Elements to the Metabalones that We Haven't Characterised?

1:03:55 How Do We Identify What We Don’t Know About Metabalones?

1:06:49 Elderly Donors (100+ Years)

1:08:51 Microbiome Promoting Health in Specific Cases of those Living Long Healthy Lives

1:09:53 Would these People Make Good Donors?

1:11:15 Alcohol Craving Post FMT

1:12:52 If Someone Has Used Alcohol Heavily but all Tests Show Good Signs, Could Their Microbiome be Protecting them? And Make Them a Good Donor?

1:15:16 Bariatric Surgery Changing the Anatomy and Changing Microbes

1:17:15 Dr Mullish’s Experience in Trying to Enhance the Probability of Success with FMT

1:18:21 Potentially 1 in 3 People Have Non-Alcoholic Fatty Changes Which May Progress in Some People to Cirrhosis

1:24:26 Is there Any Argument in Looking at a Donors Healthy Metabolic Profile?

1:25:57 Mixing Together the Starting Material Between Different Donors

1:30:14 Do we Know Why Lower Diversity Has an Impact on the Success of Stem Cell Transplants?

1:31:11 Dr Mullish’s Experience with Stem Cell Transplants Within FMT

1:37:37 Are Your Team Strong in the Conviction that Microbiome Therapies are Going to have an Impact on Cancer Patients?

1:40:46 There are Various Different Types of Responses, With There Being Full Response in Non-Responders Post FMT Which Offers Hope

1:42:19 With the Available Tool Kit Teams will be able to Decipher What Element of the Microbiome is Driving Response

1:43:45 How is the Tool Kit for FMT Going to Evolve in the Next 5 Years?

1:47:33 The Cure for many Ailments May be Living Inside Us

1:48:48 How Does Dr Mullish Respond to Questions on how to Improve Gut Health?

1:50:48 Are We at the Point Where People Can Get a Prescription For Prebiotics and Probiotics Through a Doctor Using Microbiome Profiling?

• 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 publications

• Dr 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.