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Learn more about the podcast at https://insidematters.health/ 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. 0:00 Intro 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 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 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 1:13:00 Microbial proteins 1:15:30 Anti microbial 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 - Executive summary 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 (ref) and patients undergoing treatment for blood cancer (ref) 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.