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.