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.