Better Clinical Trials: How Does Location Impact Autoimmune Research Studies?

Autoimmune research is continually evolving as the scientific community uncovers the mechanisms and unravels the pathogenesis of these conditions. While not everything is understood about autoimmune disorders, one fact that does seem to be apparent is the influence of location. Living in a specific area or eating certain foods can expose people to microflora that impacts their microbiota in meaningful ways – possibly putting them at risk or protecting them from developing certain illnesses.

In this article, we will explore some of the recent studies that examine the link between location and autoimmune function.

Influence of Diet on Immune Disorders

In 2020, researchers Alemao et al looked at how diet impacts the microbiome and the mucous barrier, and specifically, how the food we ingest influences immune disorders. They found that poor diets can influence the onset of autoimmune diseases or their exacerbation. Alemao et al showed that poor diet, environmental exposures, and other factors reduce barrier function and disrupts the turnover of mucus so that immunity becomes dysregulated. Pathogens have the opportunity to grow, microbes become poorly adapted, and chronic diseases develop.

These mechanisms and the microbiome are shaped in early life – that’s where location can come in. “Different regional diets correspond to differences in the composition of the gut microbiome,” explains Alemao et al. The researchers explain that a typical Western diet is associated with low Prevotella while a diet high in fruits and vegetables, like the usual Mediterranean diet, produces higher amounts of Prevotella.

Early Life as a Factor in Autoimmune Susceptibility

While genetic factors do play a role in autoimmune disease susceptibility, researchers Manzel et al (2014) note that there is a “relatively low concordance rate for most of the diseases between monozygotic twins suggests environmental factors as important triggers of disease.” They also point to the rapid increase in ADs in recent decades while the genetic basis has not changed. Research by Tamburini et al (2016) looked at the importance of postnatal exposures in the development of newborn immune and microbiome systems, including the prenatal environment, diet, antibiotic treatments, and environmental exposures.

Environmental Exposures and Autoimmune Diseases

Environmental exposures were also linked to autoimmune diseases (ADs) in research from Khan and Wang (2020). They looked at a range of factors including chemical-induced intestinal microbiome alterations that have been linked with the pathogenesis of autoimmune disorders. Their research found, “environmental factors account for up to 70% of all ADs. Strong evidence exists linking environmental agents, including solvents, crystalline silica, mercury, pesticides, pristine, and cigarette smoking with the development of various ADs.” While the mechanisms behind these links are not understood, Khan and Wang explain that evidence is compelling enough to deserve a thorough evaluation of their role when looking at AD pathogenesis.

Development of Chronic Diseases and Urbanization

Research has connected urbanization with changes in microbiota as well. Research by Zuo et al (2018) looked at the Westernization of diets in developing countries as well as the Westernization of lifestyle – increased use of antibiotics, elevated levels of pollution, improved standards of hygiene. They concluded that there is an impact on health and inflammatory bowel diseases.

Understanding Site Selection in Conducting Autoimmune Studies

There has been a range of studies that link environment and other characteristics associated to location with autoimmune disease pathogenesis, progression, and severity. When selecting site for autoimmune disease research, the impact of these factors and variables cannot be discounted or ignored in that personal participant history could influence microbiome and thusly impact AD in those individuals.



Resources

Alemao, C. A., Budden, K. F., Gomez, H. M., Rehman, S. F., Marshall, J. E., Shukla, S. D., Donovan, C., Forster, S. C., Yang, I. A., Keely, S., Mann, E. R., El Omar, E. M., Belz, G. T., & Hansbro, P. M. (2021). Impact of diet and the bacterial microbiome on the mucous barrier and immune disorders. Allergy, 76(3), 714–734. https://doi.org/10.1111/all.14548

Dedrick, S., Sundaresh, B., Huang, Q., Brady, C., Yoo, T., Cronin, C., Rudnicki, C., Flood, M., Momeni, B., Ludvigsson, J., & Altindis, E. (2020). The Role of Gut Microbiota and Environmental Factors in Type 1 Diabetes Pathogenesis. Frontiers in endocrinology, 11, 78. https://doi.org/10.3389/fendo.2020.00078

Khan, M. F., & Wang, H. (2020). Environmental Exposures and Autoimmune Diseases: Contribution of Gut Microbiome. Frontiers in immunology, 10, 3094. https://doi.org/10.3389/fimmu.2019.03094

Manzel, A., Muller, D. N., Hafler, D. A., Erdman, S. E., Linker, R. A., & Kleinewietfeld, M. (2014). Role of "Western diet" in inflammatory autoimmune diseases. Current allergy and asthma reports, 14(1), 404. https://doi.org/10.1007/s11882-013-0404-6

Tamburini, S., Shen, N., Wu, H. C., & Clemente, J. C. (2016). The microbiome in early life: implications for health outcomes. Nature medicine, 22(7), 713–722. https://doi.org/10.1038/nm.4142

Zuo, T., Kamm, M. A., Colombel, J. F., & Ng, S. C. (2018). Urbanization and the gut microbiota in health and inflammatory bowel disease. Nature reviews. Gastroenterology & hepatology, 15(7), 440–452. https://doi.org/10.1038/s41575-018-0003-z