Ep.07 – Professor Julian Marchesi
Episode seven of Inside Matters
The real story behind probiotics, the importance of the virome, developing analytical toolkits to study the microbiome
Professor Marchesi is an expert on the application of next generation sequencing technology and novel analytical methods to study microbial ecologies.
Key takeaways from this episode:
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.
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.
There 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 the 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 the chemicals than 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.