Relationship of PHM hypothesis to infectious diseases
Diseases that have been associated with inflammation, air pollution, and a westernized diet (cardiovascular disease, diabetes, obesity, and chronic lung disease) are some of the comorbidities associated with severe COVID-19. It has been proposed that the severe inflammatory component of COVID-19 could be related to an intensified immune reaction to components of the microbiota present in various tissues[25]. These microbes might be PHM or opportunistic pathogens that take advantage of PHM-induced immune dysregulation and thus could underlie these comorbid conditions. Up until the severe viral infection, the immune system may have been reacting to these resident microbes with low-grade inflammation. When the upregulated immune response occurs due to the acute infection, this low grade inflammatory response to the PHM might develop into an excessive inflammatory response. A similar intensified reaction to PHM might also occur in other conditions where excessive inflammatory responses occur, such as influenza and sepsis, and might play a significant role in disease progression.
PHM-induced dysregulation/suppression of the immune response might also increase susceptibility to a variety of other infectious agents. Del Poeta et al[26] notes that our ability to determine immunodeficiency is limited. Thus, relatively subtle immune defects caused by PHM might be an issue to consider.
The PHM hypothesis proposes that disease might develop in genetically susceptible individuals in the following way. PHM from the environment colonize particular areas of the body, often after a higher-than-usual environmental exposure. Acute infections or chronic stress might serve as triggering factors, which might be followed by a vicious cycle of increasing hypersensitivity reactions, increased physiological stress, barrier breakdowns, further PHM colonization, secondary infections and tissue damage.