Guillain Barré syndrome (GBS) is thought to be the leading cause of paralysis in the world, yet little is known about the factors that make one individual more susceptible to the disease than another. What we do understand is that bacteria are a key factor in development of the disease. The majority of GBS cases follow infection with bacteria or viruses (generally called 'microbes'). The best studied of these microbes is the diarrhea-causing bacterium Campylobacter jejuni, which can cover itself with human-like sugar structures to avoid being detected by our immune system. However, in some cases, the immune system still creates antibodies against those sugar structures and those antibodies trigger an autoimmune response, where the body attacks its own nerve cells because they display the sugar structure. The self-inflicted damage to the nerve cells then leads to the paralysis seen in GBS. However, in addition to these harmful bacteria, the human digestive tract is naturally filled with other bacteria that have countless benefits to the body, even contributing to the first line of defense against incoming pathogens. Since these resident microbes are present in the digestive tract from birth, they also play a key role in shaping the way that our immune system responds to organisms that enter the body through eating or drinking.
Our group has evidence that there are resident bacteria in our gut that also display the same sugar structures responsible for putting someone at risk of GBS. It is possible that these organisms can impact the development of GBS in two ways: (1) 'tolerizing' the immune system to this type of structure so an incoming pathogen is less likely to cause GBS following an infection or the opposite effect; (2) priming the immune system to be more prepared to attack the incoming pathogen that also displays these sugars making GBS more likely. Our proposal aims to study the gut microbes and antibody levels (immune system) from former GBS patients by examining their blood and stool samples. We will then compare them to people who have never developed the disease to identify patterns that may explain why only some people are susceptible to developing GBS. By figuring out which bacteria display these sugar structures, we can also develop ways of preventing GBS by altering the levels of these specific bacteria. To test what we learn from these human comparative studies, we will alter the gut bacteria of mice and determine if the contents really do impact risk of GBS. Blood from the humans and mice will then give clues regarding how human GBS patient immune systems respond differently to these microbes and why they were more susceptible to development of GBS.
GBS is a growing concern due to reports among U.S. military personnel and increased incidence rates linked to the spread of Zika virus. The incidence is also higher in low and middle-income countries, which is why we plan on studying former GBS patients from the US military as well as patients from Bangladesh. This work will provide important information toward preventing GBS and help to form a basis for development of other personalized care options.
|Effective start/end date||1/01/20 → …|
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