It’s thought that the human microbiome weighs in at around half a pound in the average person. It is a complex community estimated to contain up to 40 trillion bacteria and fungi, as well as 380 trillion viruses, which collectively play an essential role maintaining health and supporting the immune system. The gut microbiome is largest of the human microbiomes, which also include the skin, the naso-pharyngeal, the lung, and the vaginal microbiomes, and has started to be considered as a separate ‘organ’.
Although the study of human microbiomes is a relatively new area, research has already highlighted that imbalances in the microbiota play a role in chronic diseases ranging from inflammatory bowel diseases (IBD), cancer, obesity, atherosclerosis, diabetes, arthritis, allergy, and neurological disorders. What is as yet unknown, is the effect the microbial interactions have in causing such diseases.
In February 2019, the Oxford Centre for Microbiome Studies (OCMS) was launched at the Kennedy Institute of Rheumatology. Professor Fiona Powrie, Director of the Centre said: “We aim to establish OCMS as a leading centre for microbiome research in the UK. Our state-of-the-art facilities and multidisciplinary expertise provide essential technology to move beyond association studies to identify functional pathways through which microbes communicate with their hosts. This knowledge will help us harness the power of the microbiome to promote health and prevent disease.”
Jethro Johnson joined the Centre as Deputy Director in early 2020. He said: “We understand what is in the microbiome and that it has an effect on a person’s health. But there are still many fundamental principles that have not yet been worked out for the microbiome, and these questions need addressing before we get to a point where we can understand the role of the microbiome on these conditions.”
His vision is to expand access to microbiome research within the University, and also beyond in the UK and internationally. That began with building a research community across the University that so far includes 16 researchers from across 8 departments to generate deeper insights into the role of microbes across diverse environments and disease settings.
“One of the core goals for the centre is to understand what is happening at the fundamental level in the microbiome. It comes down to the basic science so we can move away from the correlative association of the microbiome with disease, towards finding a causal role. Our community of inter-disciplinary researchers brings us strength in this area. We can leverage the full power of all the academics that are around us in Oxford to develop and test explicit hypotheses around the microbiome in the context of any particular question.”
Driving technology forward is another part of the OCMS vision. The centre is one of only a handful of facilities in the UK that houses a dedicated gnotobiotic facility, in which model organisms can be studied under ‘germ-free’ conditions (i.e., in the complete absence of microbes), or following controlled introduction of specific microbes that may have therapeutic, or disease-causing effects. The Centre’s anaerobic chambers allow for the culture of different microbial agents, and the team also offers analysis of large scale, complex datasets, through a dedicated bioinformatics team with access to high-performance computing at the Biomedical Research Computing (BMRC) facility within the Wellcome Centre for Human Genetics.
“Our work with collaborators is important in taking technology to the next level. We’re aspiring towards third generation sequencing now, which will offer a paradigm shift in the field of the microbiome. We also collaborate very closely with chemistry to support metabolomics, the study of small microbially derived metabolites, and their role in particular conditions. Researchers have already been able to implicate metabolites from the gut microbiome in development of a number of diseases, such as cardiovascular disease, so they are a very important part of the picture,” said Jethro.
The level of interest in the microbiome across the University and beyond is huge. OCMS received some funding from the National Institute of Health Research (NIHR) which was used as pump priming for a number of research projects. They received 20 applications from across Oxford but were only able to move forward with nine in a diverse range of areas such as exploring the gut brain axis, and gut inflammation. They have also collaborated outside of the Medical Sciences Division, for example with start-ups at the Begbroke Science Park and with members of the Royal Veterinary College. “There’s great potential in animal microbiomes in both companion animals and the agricultural sector, for example looking at reducing methane production from the cow rumen by manipulating the microbiome. The scope is immense.”
As Deputy Director, Jethro also has the opportunity to pursue his own research agenda. He comes to the microbiome from a background in nutritional ecology, starting out as a Commonwealth Scholar in New Zealand, where his PhD looked at microbially-mediated digestion in the guts of herbivorous fish.
He subsequently moved to Oxford on a Medical Research Council Career Development Fellowship at the Department of Physiology Anatomy and Genetics, dealing with the analysis of next-generation sequence data. “My research marries these interests. I view the microbiome from an eco-physiological perspective, in particular its role in mediating environmental effects on host health, and I address this using computational genomics. I think that's a valuable perspective because I have a technical skill set in terms of computational work, and the biological insight from the more ecological aspects of the microbiome,” he said.
Jethro also spent time working with Professor George Weinstock in the US. “George was one of the leaders of the Human Microbiome Project, and I was in his lab working on the follow-up, the integrated Human Microbiome Project (IHMP). This was a fascinating study. Essentially, it was longitudinal follow up on the microbiomes of people at risk for specific diseases, so they had a preterm birth cohort, an IBD cohort, and we were working on the at risk for type two diabetes cohort.”
“I think the future of microbiome is highly cross disciplinary,” he concluded. “We have people that work in biochemistry, zoology, and plant sciences and are all making inroads into the field of the microbiome. The opportunity to draw these interests together is certainly a vision that Fiona has had for a long time, which I completely subscribe to.”