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THE IMMUNE SYSTEM
There are two main parts of the immune system, adaptive and innate. The adaptive immune system produces antibodies when the body encounters substances that contain antigens, bacteria, viruses, parasites, and fungi, or even defective cells that can turn cancerous. The antigens attach to the substance and act as a marker so that the innate immune system can send immune cells to these locations and attack the foreign substances. Later, if the host encounters the same antigens, the immune system knows how to attack it and can do so easily. The lack of antigens humans come in contact with on a daily basis has greatly affected how the immune system operates.
This immage shows some of the immune cells humans have (iBiology)
IMMUNE DISORDERS AND PUBLIC HEALTH
According to the National Institute of Health, over 7% of the US population ( 23.5 million people) suffer from various autoimmune disorders. There are over 80 different disorders, the most common being type one diabetes, rheumatoid arthritis, and lupus. Three-quarters of people who suffer from autoimmune diseases are female, and they disproportionally affect women of color. (Genentech)
In an immune disorder, the immune system gets “confused” and misguidedly attacks the host's tissue. This can be triggered by internal factors like genetics, which causes predisposition, but oftentimes, autoimmune disorders are triggered by external factors. Studies have found links to exposure to agricultural chemicals, childhood poverty, diet, chemotherapy, substance use, infection, and more. While there are treatments for these disorders, some of the most common being anti-inflammatory drugs like corticosteroids or immunosuppressants, they only mitigate the symptoms of the current flare-up rather than curing the root of this issue. This is the case because immune disorders are poorly understood and under-researched. In addition, every case is different, and the causes are usually unknown which makes treatment extremely difficult.
This diagram shows where dysbiosis from each part of the digestive system has the most impact (Frontiersin, Human gut microbiota in health and disease: Unveiling the relationship)
THE GUT MICROBIOME
Biodiversity is necessary for ecosystems for the survival of species and for ecosystem resilience as a whole. While typically we think about this in the context of, for example, a rainforest or a coral reef ecosystem, this also applies to the “ecosystems” of fungi and bacteria that exist inside organisms, called the microbiome. The gut microbiome (GM) in particular is hypothesized to be the richest, with microbial biodiversity playing a vital role in host health.
These are images of Enterococcus gallinarum, a specific bacteria that has been evolving over the past century as a result of the overuse of antibacterials. It is one of the main bacteria being studied with translocation.
It resides in the gastrointestinal tract and contains hundreds of species of bacteria. The GM is accumulated by ingesting microorganisms from foods, cultivation through infection, before birth during gestation and at birth, and in everyday life from surfaces. While modern medicine has been largely focused on killing bacteria and emphasizes what we call “cleanliness,” accumulating evidence suggests that having a microbiome that is flourishing with many different species of microorganisms is vital for the general health of the host and a lot of biomedical research has been done with this using mouse models to understand the human microbiome and how it functions.
Bacteroidetes and Firmicutes phyla are the most commonly found bacteria in a human's balanced and “healthy” GM. Still, in addition, Proteobacteria, Actinobacteria, Fusobacteria, Verrucomicrobia, and Cyanobacteria are also necessary for microbiota homeostasis. Dysbiosis refers to an imbalance in the microorganism composition in the gut and the resulting loss of t-cell equilibrium. Such a lack of microbial balance can lead to a gut environment that causes certain bacteria to undergo a phenomenon called “within-host evolution” where, due to changes in the gut, microorganisms may evolve rapidly, and possibly cause harm to the host. This phenomenon is key to understanding the close link between the microbiome and immune function and will be expanded on in sections below.
A lot of evidence has suggested that one of the main causes of immune disease is dysbiosis. In particular, researchers believe that gut imbalance can cause both bacteria to evolve, and for the barriers that en-case the intestine to be weakened to enable the bacteria to escape, the term for this is translocation. Diet, medication, and antibiotics could be the reasons for these changes, and trying to rebalance the gut microbiome, and strengthening the intestinal lining could be the cure for autoimmune disease. This could mean there could be non-invasive and not harmful treatments to put an end to the chronic inflammation many patients would otherwise have to live with indefinitely.
MY PROJECT
For my project, I hope to study bacterial evolution, translocation, and the subsequent triggering of the immune system. I would like to understand how the composition of bacteria in our guts, the linings to our organs, and the effects of drugs, preservatives, irritants, and antibiotics are essential in taking major steps to minimize this public health issue and key in understanding auto-immune disorders. My project ideas range from culturing specific bacteria known to translocate and trying to see how many generations it would take for them to evolve under dysbiosis-adjacent conditions, to studying the blood and liver tissue of diseased mice to test for translocated bacteria or evidence of overproduction of immune cells.
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