Inside Matters

Episode 007 - Professor Julian Marchesi – microbiome analysis, probiotics, microbial therapeutics, the microbiome in cancer

This was a wide-ranging and fun conversation that covered a lot of ground. We could have kept going for a lot longer. 
Professor Marchesi is an expert on the application of next-generation sequencing technology and novel analytical methods to study microbial ecologies.
Our understanding of the microbiome and the genomic potential of the microorganisms within the microbiome has vastly increased due improvements to DNA sequencing technology and associated reductions in the cost of sequencing a genome. 
DNA sequencing has allowed us to create inventories of microbiomes based on the source of the sample collected: stool, sputum etc. These inventories allow us to understand datasets generated from research studies. However, Professor Marchesi describes there being microbial ‘dark matter’ within the microbiome, in which dark matter is defined as a DNA sequence that has never been definitively linked to a strain of bacteria that has been cultured in a pure culture setting and phenotypically characterised. This is an inherent limitation to our understanding. 
There are a variety of technologies and approaches available to study the microbiome beyond using next-generation sequencing technology. They can be broadly described and categorised as ‘omics’. Each of the Omics describes a different technique e.g proteomics (study of proteins) metabolomics (study of metabolites) etc. Researchers combine these techniques to study microbes and ecosystems, but there is still a lot that we do not know. To exemplify this, Professor Marceshi referenced E.coli, the most well-studied microbe on the planet. Despite all of the research that has been conducted to date to characterise E.coli, only 40% of its genome has been mapped to particular functions. 
Professor Marchesi and colleagues at Imperial College have pioneered the application of intestinal microbiota transfer (IMT) to different diseases, including recurrent C.difficle infection and patients undergoing treatment for blood cancer.
Looking into the future, Professor Marchesi believes that probiotics will be rationally described and selected based on specific microbiome profiles in the intended recipient (s). He also believes that donor screening for IMT will evolve and that robust analysis of the microbiome in patients before and after IMT procedures may reveal clues about the mechanism of action of IMT, which, in turn, may result in the discovery of new drug candidates. 
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Some facts from the conversation with Prof Marchesi : 
50% of stool biomass is bacteria. It is for this reason that we alternate between being greater or less than 50% human/microbial.
They're roughly 150 species in the gut of any person and 1000’s different species. 
The microbiome has been shown to have an impact on drug metabolism and safety/tolerability/efficacy.
There are bacteria that can cause uncontrolled growth in plants - there may be parallels between what happens in plants and what happens in human cells.
There are distinct differences between the microbiomes in the small and large intestines, as well as significant differences in immunology. The differences in microbiome profile primarily relate to differences in food sources. 
Microbes can be described as factories that produce chemicals and proteins. We know more about chemicals then proteins such as short-chain fatty acids (an energy source for colonocytes acetate, proportionate, butyrate and valerate. Professor Marchesi describes them as anti-inflammatory, anti-proliferative and anti-carcinogenic - i.e they reduce the risk of cancer and help with your mental health.
Every one bacteria has ten viruses trying to predate it in the gut. Viruses are the most abundant organism on the planet. There are more viruses on the planet than there are stars in the Universe. 
Timecodes:
00:00 Introduction
1:15 Silent retreats and isolation chambers
3:41 Artificial intelligence 
6:10 Julian’s journey into the microbiome 
9:10 Phylogeny and morphology 
12:18 Evolution of DNA sequencing 
13:40 Personalised medicine  
14:51 The human genome project 
15:33 Finding your way as a scientist 
16:05 Culture-independent approaches and culture approaches 
22:08 Dark matter
26:24 Naming bacteria after people
27:30 Omics and gene profiling 
30:22 Drug metabolism and microbes 
34:51 Is the microbiome the passenger or the driver?
36.06 Colon cancer and cancer in plants 
40:24 Intracellular bacteria 
41:10 Probiotics including the segment relating to a generic probiotic and IBD drug 
45:25 Single strain vs a complex ecosystem 
46:26 Small intestine vs large intestine microbiomes 
51:29 Probiotics 
54:10 Post-antibiotic use microbial therapy
55:52 Donor screening for intestinal microbiota transfer good clip of EnteroBiotix 58:40 where I talk about scale, would be good to clip 
1:00:52 Using metabolomics to screen donors 
1:01:25 What is metabolomics?
1:03:50 Microbial metabolites 
1:05:30 Reverse engineering FMT/IMT
1:06:35 Bariatric surgery
1:08:30 Obesity and food cravings    
1:11:06 Maternal transmission and the early life microbiome , also good clip on short-chain fatty acids 
1:13:00 Microbial proteins, 10% of world's biomass is below the sea floor and it’s bacteria, good clip. Level of the adaptation is really good
1:15:30 Antimicrobial resistance
1:18:00 Fungi in the microbiome 
1:19:10 Blastocystis hominis 
1:20:50 Phage and fungi in the microbiome
1:29:22 Understanding how IMT / FMT works  

Episode 006 - Dr Gianluca Ianiro – the concept of the microbiome clinician, intestinal microbiota transfer, the future of microbial therapeutics

Learn more about the podcast - https://insidematters.health/
We talk with Dr Gianluca Ianiro about the concept of the microbiome clinician, intestinal microbiota transfer, and the future of microbial therapeutics
Dr Gianluca Ianiro, is a gastroenterologist at the Digestive Disease Center of the Fondazione A. Gemelli IRCCS and an adjunct professor in gastroenterology at the Università Cattolica del Sacro Cuore in Rome, Italy.
Dr Ianiro’s research focuses on clinical and translational studies on intestinal microbiota. He has established himself as a leading clinical and translational investigator focusing mainly in the field of intestinal microbiota with more than 180 peer reviewed publications including some of the best referral journals in Gastroenterology and Internal Medicine, including NEJM, Nature Medicine, Lancet Infectious Disease, and has received several research grants in support of his innovative research.
Dr Ianiro has been the secretary or the leader of several international consensus conferences on fecal microbiota transplantation. He was in the Young Talent Group and in the Research Committee, of the UEG (United European Gastroenterology), and has been awarded as UEG Rising Star in 2020. His current research is focused mainly on disentangling the rules of donor microbiome engraftment and on investigating FMT in other indications beyond C. difficile.
Intestinal microbiota transfer, also known as IMT, FMT, or a stool transplant, is a medical procedure that involves the transfer of microorganisms from a healthy donor into the intestinal tract of a recipient. IMT is an established treatment for recurrent C.difficile infection, with the first randomised controlled clinical trial published in 2013.
Since the first landmark clinical trial was published, there have been additional RCTs published in ulcerative colitis (a form of inflammatory bowel disease), irritable bowel syndrome, and metabolic syndrome. Other pilot studies have been conducted on patients suffering from cancer and who are undergoing immune system-stimulating treatment (immunotherapy). More research is required before IMT becomes an established therapy in these patient populations. 
We do not fully understand how IMT works. The available evidence suggests that in successful IMT’s, donor microorganisms persist in the intestinal tract of the recipient after IMT. This process is called engraftment. The determinants of engraftment are an area of active scientific research. 
Dr Ianiro and colleagues are pioneering the concept of a microbiome clinic in which doctors use microbiome data to inform clinical decision-making for patients. He believes that clinics like these are the future of modern medicine. 
Dr Ianiro recommends diets that contain minimally processed and micronutrient-dense foods for the microbiome and gut health. Fruits, vegetables, and high fibre. He does not recommend probiotics for members of the general population. 

Episode 005 - Dave Stevens – microbial therapeutics, pharmaceutical manufacturing, building a best-in-class contract development manufacturing organisation

Learn more about the podcast here - https://insidematters.health/
David (Dave) Stevens is the CEO of Arranta Bio, a leading contract development manufacturing organisation that specialises in advanced therapies, including microbiome therapeutics. ArrantaBio supports many of the world's leading microbiome companies that develop and manufacture novel drugs for the benefit of patients around the world. 
Dave was formerly the Senior Vice President and Head of AMRI’s Drug Product business unit where he had P&L responsibility for sales and operations. During his tenure, he led the division through a period of significant growth and capacity expansion. Before leading the division, Dave held senior leadership roles at AMRI including Vice President, Sales & Marketing and General Manager of a sterile dosage form development and GMP manufacturing facility.
Dave is a native Scot that is passionate about building Scotland into a global leader in life sciences, as well as being a big believer in the power of the microbiome to benefit health. 
- 0:00 Intro- 1:14: jet lag, training, intermittent fasting- 3:40 what motivates you to work- 5:00 moving from startup to scale up- 5:30 challenges in microbiome manufacturing / microbial fermentation- 5:58 what is a contract development manufacturing organisation (CDMO)?- 7:00 challenges for the microbiome field- 7:30 the microbiome as a therapeutic target- 09:40 intermittent fasting- 10:33 health span and lifespan- 12:37 what does ArrantaBio do- 14:00 mRNA technology - overcoming challenges and realising promises- 17:35 a Scottish success story- 21:18 mindset in Scotland vs USA- 27:15 how to become life sciences capital of the world- 32:27 first approved microbiome therapies- 35:12 characterisation of the microbial ecosystems- 37:20 dogs and depression- 38:10 types of microbiome therapies- 42:36 competing with other CDMOs- 46:02 manufacturing probiotics- 47:10 Good manufacturing practice- 48:50 Probiotics- 50:41 lost the screen- 51:50 innovation in the microbiome field- 53:00 lyophilisation- 54:24 Fermentation systems- 55:25 EnteroBiotix- 57:00 the gut-brain axis- 58:35 how good gut health makes you feel- 1:00:02 Gene therapy and the costs of cures- 1:03:00 the start of ArrantaBio and vision for the future- 1:08:00 buying the best to be the best- 1:10:30 leading organisations- 1:11:20 being a leader- 1:15:10 spending time with the best to be the best- 1:17:30 being a vision and mission-driven company- 1:17:45 the future of ArrantaBio
 
 

Episode 004 - Andy Scott – gut health and bodybuilding, gaining muscle, losing fat

Visit the Inside Matters website for more information about the podcast and the guests - https://insidematters.health
Andy Scott is one of the UK's top amateur bodybuilders. In this episode, we dive into the world of bodybuilding and discuss in detail the psychological processes bodybuilders go through, along with the science of diet and the role the gut biome plays in their health and training performance.
Bodybuilding is the pursuit of aesthetic perfection, with perfection meaning different things to different people. Many of the core principles that are associated with success in bodybuilding can be applied to microbiome improvement and gut health. These include consistency, discipline, eating minimally processed micronutrient-dense food, training muscle groups and experimenting with diets to figure out what works best.
Prioritising gut health is becoming more and more popular in bodybuilding, with top athletes now undertaking elimination diets, taking probiotics and eating more ‘microbiome-friendly foods.
Some of the topics covered in this conversation:
Top bodybuilders take decades to build their physiques. Consistency, forming habits and discipline were recurring themes associated with success throughout the podcast.
Bodybuilding has evolved over time, just like other sports, with improvements to techniques, methods, supplements and systems.
Andy competes within the super heavyweight division (225lbs+) at 3% body fat. To put that into context, the average male is 19/20% body fat and typically abs become visible at 9/10% body fat.  Bodybuilders like Andy achieve this through year-round intense training and dieting. There are only a small number of days/weeks in a year where a bodybuilder doesn’t feel full all the time (growth phase) or is hungry all the time (dieting phase).
To achieve maximum muscle growth, bodybuilders train muscles to failure (when it is not possible to do another rep) with a controlled tempo (a slow eccentric, typically 2-3 seconds, and a fast concentric). This training philosophy can be adopted by anyone wanting to improve their physique and not necessarily only those who want to be a bodybuilder. Andy thinks that it is still possible to build an amazing physique without training to failure, but it would take twice as long.
In Andy’s opinion, the fastest way to lose fast is a low-carbohydrate diet. Some people recommend a zero-carbohydrate diet. However, to retain muscle, maintaining carbohydrate intake is important. Slowly decreasing calories in a tapered fashion while maintaining intense training is the best way to lose fat and preserve muscle.
Andy implements elimination diets for himself and his clients with a view to improving gut health and reducing gastric distress. In these diets, Andy removes a food source for 3-5 days, sometimes longer, in parallel with tracking how the person feels. Anecdotally he sees improvements in performance in the gym because of diet modification through elimination diets.
In terms of foods that typically cause problems, he finds that oats and broccoli can be a problem for his clients. Simple changes like moving the oats to a guaranteed gluten-free source and moving to another vegetable type can have a positive impact. 
Bodybuilders can take up to 20 weeks to get show ready. Towards the end of the show, they lack energy. So much so, that even getting up off a sofa to make a coffee is a challenging task.
Andy eats 6,500 calories a day from micronutrient-dense, unprocessed food. He prioritises animal sources of protein. Interestingly, Andy is not aware of any top professional bodybuilders being vegan or vegetarian. He does have clients who make good progress on these diets though.
Andy and James discussed something called ‘if it fits your macros’ which is a diet philosophy underpinned by hitting macronutrient targets through any food/drink sources i.e diets are not fixed/set in terms of food choices. It was agreed that food sources and the quality of food is equally if not more important than simply hitting a calorie/macronutrient target.
Andy’s advice to those getting started is to start slow and to make small changes that you can stick to every day and consistently e.g walking for 30 minutes each day, building up to walking and then lifting weights. The same can be said for diets.

Episode 003 - Dr Morgan Langille – microbiome bioinformatics, DNA sequencing, metagenomics

Dr Morgan Langille, an expert in bioinformatics, talks about developing novel technologies and techniques that enable a better understanding of human-microbial interactions. 
 
Dr Langille discusses advances in the microbiome field as well as combining computer science and microbiology to lead to new therapeutics and diagnostics.
 
Episode Time Stamps
00:00 Intro
00:30, How Dr Langille got into the field of the microbiome
04:30, Gene duplication and reverse transcription
05:48, What is bioinformatics?
06:34, The evolution of bioinformatics 
09:30, Genomic islands
1:04 - Phages
14:30 Dr Langille’s first bioinformatics tool 
16:00 Bacterial genome libraries 
18:20 Extremeophilic bacteria
19:00 Will there be bugs in space
21:42 Bacteria on Mars 
22:15 Human microbiome diversity 
23:30 Number of human cells vs microbes in the body 
25:00 Genomic diversity within the microbiome 
28:00 Perfect bioinformatics 
33:40 Bioinformatics and microbiome research
34:37 Short read vs long read sequencing 
45:30 Shotgun metagenomics 
48:00 Bioinformatic tool development 
1:01:00 Differences in bioinformatic tools and impact on research 
1:06:00 Solutions to current technology challenges in bioinformatics
1:10:06 Tools that Morgan has developed 
1:08:05 PICRUSt - bioinformatic tool 
1:18:35 Jarvis - bioinformatic tool 
1:24:00 Talent wars for bioinformatics 
1:26:36 Machine learning and AI
1:32:51 Colorectal cancer and AI 
1:36:35 Is blood sterile?
1:38:00 What does the future of medicine look like 
1:40:51 DIY FMT
 

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.

Episode 001 - Dr Richard Hansen - microbial therapeutics and paediatric IBD

Visit our website to learn more about Inside Matters - https://insidematters.health/episodes/dr-richard-hansen
 
Watch the conversation on our YouTube channel - https://www.youtube.com/watch?v=nZma2Kh-umQ&ab_channel=InsideMattersPodcast
 
Dr Hansen is a Consultant Paediatric Gastroenterologist at the Royal Hospital for Children in Glasgow and an Honorary Clinical Associate Professor at the University of Glasgow. He is a principal investigator within the Bacteria, Immunology, Gastroenterology and ‘Omics (BINGO) group at the University which developed the CD-TREAT diet for Crohn’s disease.
 
His clinical interests are inflammatory bowel disease (IBD), paediatric endoscopy and Helicobacter pylori. His main research interest is the gastrointestinal mucosal microbiota and its importance in paediatric disease, particularly IBD. He is especially interested in the molecular characterisation of the microbiota and its subsequent modification for the purposes of therapeutic effect via microbial therapeutics.
 
In this episode, we discuss treating IBD in children, using entirely liquid diets to reduce inflammation, and developing novel strategies that target the microbiome to treat IBD.
 
1:06 - Intro
1:56 - Interview Starts
2:27 – How to study the microbiome – analytical methods and study types
3:22 - How has microbiome science changed over the last 5 years?
5:13 -  What is Exclusive Enteral Nutrition (EEN)?
7:39 -  What is Inflammatory Bowel Disease (IBD)?
10:18 - Why are people getting IBD earlier in life?
14:54 - Is there different immunology between Crohn's disease and IBD?
17:07 - How has the perceived importance of the microbiome changed in IBD?
21:48 - How did all of this influence your PhD? 
26:14 - Are we missing something with the current microbiome studies?
29:17 – The Bristol Stool Score
29:53 - Do you think that the microbiome drives inflammation in the gut?
34:01 – The Appendix 
39:15 – Using the microbiome to predict IBD?
46:16 – Faecal microbiota transplantation (FMT)
49:03 – FMT in UC – studies published to date.
52:17 – Super donors in FMT
59:17 – The 16S gene
1:03:06 – The microbiome analytical toolkit
1:07:55 -  AI and large populations
1:09:19 – The implantation of machine learning
1:10:39 - Are clinicians trained in how to use AI
1:13:01 - Discussion on the application of FMT in paediatric populations.
1:14:22 - Infants, diet and gut health.
1:18:01 – Further discussion on FMT in paediatric populations.
1:20:44 - FMT donor screening processes. 
1:22:21 – Donor selection for paediatric FMT.
1:26:30 – Potential risks associated with FMT. 
1:29:19 - Can FMT or other microbial therapeutics replace immune system dampening therapies?
1:31:13 - When IBD is at its worst, what is it like?
1:36:01 - What do we do about the EEN diet and Crohn’s disease?
1:38:20 - Which element of EEN is driving the positive effects in Crohn’s?
1:42:27 - How do we create a less socially restrictive diet than EEN but keep the benefits?
1:44:44 - What is the ultimate aim of CDTreat? 
1:47:19 - What is the relative importance of bacteria versus other components of the microbiome?
 
Key takeaways from this episode:
 
There has been an explosion of interest in the microbiome in recent times as it is becoming it easier and easier to analyse the microbiome through analytical methods that do not involve traditional culture techniques - which are labour intensive and relatively slow. 
 
The field of microbial therapeutics is still in its infancy. There are many ongoing clinical trials into new ideas. Richard is hopeful that these trials will result in new treatment options for patients. 
 
Inflammatory bowel disease is a chronic (long term) condition characterised by inflammation in the gut. There are two main forms of IBD, Crohn’s disease and Ulcerative Colitis. Crohn’s disease can affect any part of the intestinal tract, from mouth to anus. UC only affects the last part of the gut - the colon. 
 
There is a microbiome that lives within the lumen of the gut and on the surface of the intestine (mucosa). Richard’s analogy for this relationship is that they are like a beach and an ocean – they are different but inextricably linked. 
 
The incidence (when the disease first starts) of IBD across the population seems to be occurring earlier and earlier in life. At the start of Richard’s career it was rare to see a patient below the age of five presenting to hospital with symptoms, now days it is becoming more common. The environment and its impact on the microbiome may be the key driver for this. There are clear changes that are observed in microbiome studies in patients with reduced IBD, namely: reductions in diversity (how many bacteria are there and how evenly are they spread), and increases / decreases in particular bacteria. 
 
Exclusive internal nutrition (EEN) is a term used to describe a 6-8 week course of an entirely liquid diet. The data suggests 4 out of 5 paediatric patients suffering from Crohn’s disease enter remission (where the gut is healed and there is no active disease causing symptoms) after a course of EEN. It thought that the longer the course of EEN the more effective it is. 
 
EEN is becoming much more popular in adult therapy, however its uptake is limited due to social constraints. Richard and a team working at the University of Glasgow are developing a less socially restrictive diet that mimics the effects of EEN. The programme of work is called CD-treat. 
 
Intestinal microbiota transfer (IMT) involves the movement of microorganisms from one person into another with the intention of treating a disease. Six randomised controlled trials have been published in UC so far, with a definite signal towards IMT being effective. Richard is hopeful that these studies will pave the way for new treatment options in IBD. 

Extreme Microbiomes and Microbes in Space!

Visit our podcast's website to learn more - https://insidematters.health/
Watch the podcast on YouTube.
 
Expect the unexpected in space microbiology! There are microorganisms that have adapted to survive in the most extreme environments. These microbiomes are being analysed to figure out what might be happening in space, especially with those that have been found to survive up to 3 years. What would happen if a human came into contact with them on another planet?

This is Inside Matters - An Introduction to Our New Podcast

Welcome to Inside Matters, the gut health podcast featuring conversations with the most forward-thinking minds in health, fitness, science, nutrition and business. In-depth discussions about how our gut microbiome impacts our health, well-being, mood and more. Inside Matters was conceived by microbiome expert Dr James McIlroy as a platform to raise awareness of the importance of the gut microbiome. Our aim is to inspire and educate listeners around the world about the importance of gut health, equipping them with the knowledge they need to transform their lives for the better.