Post-hunter-gatherer era microbes
Ever improving methods in recent decades are allowing increasingly
subtle and delayed effects of microbes to be studied. Tissues of the
human body that were thought to be sterile in healthy individuals have
been reported to contain microbial communities. Examples include
microbiotas found in the blood[45–47], lungs[48], synovial
fluid[49] and possibly even the brain[50–54]. In addition,
there are likely other microbes that are too low in abundance to be
detected using current methods[25]. Although some researchers
attribute these findings to laboratory contamination, other researchers
describe the careful use of controls and the differences founds in
microbial communities between controls and patients[55].
Man-made or processed products and toxic chemicals do not seem conducive
to significant levels of microbial survival; however, the adaptability
of some microbes has now been demonstrated in numerous extreme
environments. It may be that the only sterile places on earth are a few
laboratory cleanrooms, some hot springs, volcanoes and areas over 150
degrees Centigrade deep in the earth[56]. Scientists at NASA have
found new microbial species in their cleanrooms[57]. Some bacterial
strains have even been found to use cleaning products as their fuel
source[58].
As discussed above, the PHM hypothesis proposes that a subset of low
abundance PHMs are important in human disease. The ability of some
environmental PHMs to colonize or infect animals could be enhanced by
dual use virulence[59]. This occurs when microbes have evolved means
to survive inside of their single-celled predators and this allows them
to survive inside human cells.
It has been suggested that virulence in animals is of questionable value
to many microbes[60]. Thus, low virulence microbes may be common. A
number of examples of potentially low virulence environmental PHMs are
discussed below.
Some examples of PHMs have been found in high salt conditions. For
example, halophilic Archaea[61,62] and bacteria[62] have been
found in table salt and in the human digestive tract. Fungi from the
genus Wallemia are found in salt-preserved fish[63]. Human exposure
to such halophilic microbes was likely low before salt preservation.
The probable PHM, Mycobacterium immunogenum, found in metalworking
fluid, caused hypersensitivity pneumonitis in some machinists[64].
The PHM hypothesis suggests that there may be some degree of
colonization of this species in the lungs of the affected workers.
Tobacco smoke has been found to be a rich source of microbes, including
potential pathogens, and further research is needed to determine their
role in diseases like chronic obstructive pulmonary disease
(COPD)[65]. Even smoke from wildfires[66,67] has viable
microbes, and their effects need more study.
Researchers are beginning to look at the pathogenic potential of air
pollution associated microbes. Particulate matter that is 2.5 um or less
is a source of microbes that could lead to pathological
effects[68,69]. A study found that the proportion of pathogenic
species in air samples increased with air pollution levels associated
with urbanization[70]. Detection of 142 new microbial genera in the
pharynx followed a severe air pollution event[71].
A review of indoor environments associated with water highlights the
many relatively novel and extreme conditions that microbes are exposed
to in buildings[34]. As mentioned above, recent work has found that
fungal taxa that tolerate multiple extreme environments tend to include
more opportunistic pathogens[34].
Many extreme conditions, such as high temperatures, dry conditions, and
cleaning products found in the built environment would prevent survival
of many microbes. However, other microbes that tolerate extremes would
likely increase under the high selection pressure of the extreme
conditions. The human immune system response to microbes often creates
another extreme environment (e.g., production of oxidants). Thus,
microbes’ evolved toleration of extreme environmental conditions may be
advantageous for their survival within humans.
Research shows that dishwashers are inhabited by a polyextremotolerant
type of black yeast that is an opportunistic pathogen[34]. In
addition, a greater level of allergy in households that use dishwashers
compared to those that use traditional hand dishwashing was
found[72]. More microbes surviving the hand dishwashing has been
suggested to be responsible for the lower rate of allergy. This is in
accord with the altered microbiota hypothesis, which proposes that
greater microbial diversity is protective.
Alternatively, the PHM hypothesis might suggest that dishwashers
typically contain more polyextremotolerant microbes that are capable of
colonizing humans, and that could increase allergy. Polyextremotolerant
PHMs from the dishwasher might colonize human tissues and lead to
allergic reactions. However, it should be noted that the difference in
allergic disease was not large, and there are many possible confounding
factors, so it would be premature to make conclusions with regard to
dishwasher use[73].
In general, a problem with these types of observational studies is that
there is confounding between lowering the total microbial levels and
increasing overall microbial polyextremotolerance. Cleaning and other
factors that reduce total microbial levels create more challenging and
extreme conditions for microbes, likely selecting for the more
polyextremotolerant taxa.
Thus, other types of studies will be needed to distinguish the effect of
the cleaning-related reduction of microbial diversity from the increase
in polyextremotolerant PHMs that could occur. In any case, the two
explanations are not mutually exclusive. The lower diversity could be a
cofactor that increases polyextremotolerant PHMs’ ability to survive in
the environment and/or colonize humans.
The distribution patterns of PHMs are not likely to be simple. Even
without extensive cleaning, including in natural environments, PHMs that
could colonize humans and contribute to disease could be present. For
instance, PHMs might be in the soil, as a result of factors that
introduce or select for PHMs, such as air and water pollution.
Another example of the potential role of PHMs is related to the
association between bacterial virulence and antibiotic
resistance[74]. Antibiotics are another factor that create an
extreme environment that microbes are selected to tolerate. Thus,
antibiotics might increase the numbers of pathogenic polyextremotolerant
microbes able to colonize/infect the human body. The highly virulent
antibiotic resistant microbes are known. However, antibiotic use may
also result in other, lower abundance PHMs, with more subtle effects. An
example is the cell wall deficient forms that are created under adverse
conditions, such as certain antibiotics[40,75–77].
The PHM hypothesis takes the perspective that microbiota changes have
been occurring for thousands of years alongside human cultural changes.
The most significant changes likely occurred when populations began
forming more permanent settlements and food processing was
adopted[2]. In the following centuries, agriculture, large
settlements and mining of metals presumably began changing microbial
exposures even more. For instance, food storage would lead to increases
in some food-associated microbes (e.g., fungi causing ergotism).
However, the PHM hypothesis proposes that the known microbes
contributing to disease are only the most easily detected, and there are
many more awaiting discovery and characterization.
Thus, the PHM hypothesis is able to explain why many of these CIDs were
present at a low level before the modern, more hygienic, antibiotic
era[78–80]. The earlier presence of these diseases could have
resulted from changing PHM exposures in the post-hunter-gatherer era.