Osborne Laboratory - Feb. 04, 2022
Neuro-Immunology Researcher, PhD Candidate
Naomi is a PhD student studying neuro-immunology in the Osborne and Horwitz Labs at UBC. She completed her BSc at UBC in honours Microbiology and Immunology, during which Naomi had the opportunity to publish a UJEMI-PEARLs article.
Naomi’s research project aims to study the immunological changes that occur following various microbial, viral, and helminthic exposures, and how these changes may alter susceptibility to multiple sclerosis.
While the exact cause of MS remains elusive, we do know that MS is caused by a combination of genetic and environmental factors. In the Osborne lab, we study different environmental exposures that impact the immune system to ultimately affect disease development in a mouse model of MS. My research focuses on 3 main topics: the ability of a specific kind of dietary fibre (guar gum) to limit inflammation and reduce MS-like disease; the neuroimmune-modulatory effects of infection with helminths (i.e. parasitic worms); and how the microbiome changes with age to affect MS-like disease severity and progression.
This field is rapidly evolving, and there still seem to be more questions than answers. There is clear evidence of the microbiota impacting brain development and function in general, but how this relates to MS is still a huge and active area of research. People with MS can have a dysbiotic microbiome, which means that their gut microbes are different in some way from those of healthy controls. The exact nature of what these changes are, however, isn’t clear. While we can try to identify what these microbes are, we can also evaluate the different genes that these microbes express which changes the biochemical processes they can perform. Microbes break down dietary components and host-derived molecules into various chemicals that interact with the immune system, including short-chain fatty acids, amino acid derivatives, and bile acids. Each of these microbiota-derived metabolites has been shown to be altered in MS patients and can have disease-modifying effects in animal models of MS. There are numerous pathways through which these molecules could be affecting the central nervous system, all of which make up the “gut-brain-axis”, which is a complex network of communication that relays signals bidirectionally between the gut and the central nervous system. Some of these pathways include microbial products entering circulation to cross the blood-brain barrier and directly interact with the brain, by influencing immune cells to alter the inflammatory response, or by affecting nerves in the gut (the enteric nervous system) to relay signals to the brain.
Several lifestyle factors have been implicated in susceptibility to MS, including smoking and obesity. People who have ever smoked (or been exposed to second-hand smoke) are at a higher risk of developing MS, and people with MS that smoke tend to have more active MS or worse disease progression. Obesity is also associated with increased risk of MS, potentially due to the increased low-grade inflammation that occurs with excess adipose tissue. Similarly, diet can heavily impact inflammation, and thus risk of MS. Diets high in fat may promote inflammation, while diets rich in vegetables and fibres can help to limit inflammation.
Infections are a major immune-modulating event that can affect susceptibility to MS, either in a protective or pathogenic capacity. Epstein-Barr virus (EBV) is one such infection that is tightly linked with development of MS, where prior infection with EBV seems to be a pre-requisite for developing MS. The mechanisms of this interaction remain elusive, but it could be happening through changing how immune cells are activated. On the other hand, infection with helminths causes an anti-inflammatory immune response that may protect from MS. Part of my research involves evaluating how the immune response generated by helminth infections protects the central nervous system from inflammation.
How these factors may interact with each other to promote disease is not well understood. Obviously a single environmental factor alone cannot trigger MS, since most people who smoke, are obese, have a less nutrient-dense diet, or are infected with EBV do not go on to develop MS; nor do all people with MS have these specific risk factors. A combination of these factors and others may all work together to create a “perfect storm” of inflammation to cause MS in a genetically susceptible individual.
A lot of my work focuses on environmental exposures that may prevent MS in the first place, such as infection with helminths or by eating dietary fibres. Understanding how these environmental factors affect the immune system may prove useful for discovery of new drug targets or metabolites that could be used therapeutically. In addition to treating people that already have MS, understanding the cause of MS will have great benefit for its prevention and lowering the overall incidence of MS. For example, recently the link between EBV infection and MS has been solidified, which has renewed the push to develop an EBV vaccine – if people don’t become infected with EBV at all, maybe the incidence of MS will decrease dramatically. The ultimate goal is to prevent MS from happening in the first place.
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I did my undergraduate degree here at UBC, and I was lucky enough to have a fantastic undergraduate research experience doing MS research studying the role of EBV infection in animal models of MS. I very quickly realized how little we actually know about the cause of MS, despite it being such a prevalent disease. My eyes were opened to the many different infections, gut perturbations, and exposures that alter the immune system, and thereby could have an impact on MS. This a field in which there always seems to be a new avenue to explore and questions to be asked, which itself helps keep my motivation and enthusiasm for this work, since there is so much to be discovered.
As a “basic” researcher who works with animal models and cell culture, I rarely have an opportunity to interact with people who have MS. Both the MS research community at UBC and the MS Society of Canada do an excellent job of ensuring that scientists working on all sides of the problem have a chance to interact with each other as well as with people with MS to hear their stories and share the progress that we make behind the scenes. The optimism and courage of people with MS, and their enthusiasm to engage with the research community is really inspiring.
