Abstract
This article discusses a variant of the altered microbiota hypothesis, the leading hypothesis to explain the increase in allergic/autoimmune/inflammatory diseases with westernization. Instead of emphasizing the microbes that are missing/reduced due to westernization, this article focuses on those that are relatively novel. Environmental microbes encountered in association with a pre-agricultural lifestyle would presumably be the most coevolved with the human immune system, and thus they would be less likely to promote debilitating chronic disease. Post-hunter-gatherer era microbes (PHM) are microbes that are encountered more frequently and/or at higher levels since humans ceased to live as nomadic hunter-gatherers. Research will be discussed that suggests that some PHM suppress/dysregulate the immune system, potentially causing chronic inflammatory diseases and increased vulnerability to severe infections. PHM colonization or infection, hypersensitivity reactions and associated chronic stress could significantly impact multiple diseases. Exploration of this hypothesis might generate insights into pathogenic mechanisms and improved treatment approaches.
Introduction
This article proposes an extension of the altered microbiota
hypothesis[1], which is the dominant hypothesis to explain the
increase in many chronic inflammatory diseases in the last 75 years in
association with westernization. The altered microbiota hypothesis is an
updated version of the hygiene hypothesis. The hygiene hypothesis
suggested that the recent increase in allergies is due to reduced
exposure to pathogens. Instead, the altered microbiota hypothesis
proposes that it is primarily a reduction of commensal and environmental
microbes that we coevolved with that is responsible for increased rates
of chronic inflammatory diseases.
The absence/reduction of certain coevolved microbes likely plays an
important role; however, this article focuses on microbes that are
relatively novel. The category of post-hunter-gatherer era microbes
(PHM), as discussed here, comprises microbes that are encountered more
frequently and/or at higher levels since the advent of agriculture and
permanent settlements.
The microbial communities (microbiotas) that humans have been exposed to
have changed as human activities have changed. The most intense and
rapid changes in these microbiotas likely occurred recently in
association with westernization and industrialization. A large
proportion of the human genetic makeup evolved during the 200 million
years during which humans and their mammalian ancestors lived as
hunter-gatherers or gatherers. Microbes commonly encountered in that era
would presumably be the most coevolved with the human immune system and
would thus tend to cause less disease and/or be beneficial. In contrast,
humans are now exposed to many microbes that they did not coevolve
with[1]. It is proposed here, in the PHM hypothesis, that some
proportion of the less coevolved PHM suppress/dysregulate the immune
system, contribute to multiple chronic inflammatory diseases and
increase vulnerability to severe outcomes in acute infections through
their colonization or infection and accompanying hypersensitivity
reactions and chronic stress.
Microbes could be considered to be PHM due to being novel, such as
mutated strains found in association with newer products/substances or
novel conditions[1]. Alternatively, microbial species or strains
could be PHM due to being increased by changing lifestyles (e.g.,
intestinal Candida albicans overgrowth due to factors such as high
dietary refined carbohydrates and antibiotics).
The PHM hypothesis focuses on the sources of microbes that may
contribute to disease and emphasizes microbes’ cross-reactions with
varied internal and external antigens. In addition, it integrates the
environmental chemical (xenobiotic) hypothesis with the PHM hypothesis
by noting the likelihood of PHM being associated with chemicals from
certain occupations and air pollution from burning fossil fuels[1].
In addition, it is compatible with the cold chain hypothesis that links
Crohn’s disease with cold-tolerant bacteria (e.g., Yersinia spp and
Listeria spp) in refrigerated food[2]. PHM are more likely to be
present in certain types of food consumed commonly in westernized
societies, including refrigerated and ultra-processed
foods/beverages[1]. Microbes associated with food additives are also
potential sources of PHM (e.g., halophilic Archaea from salt[1,3]).
The term westernization, as used here, refers to factors associated with
a modern lifestyle that may be associated with health effects. It
includes a sedentary lifestyle and increased exposure to
xenobiotics/pollutants. New exposures from western medicine, like
antibiotics, are also included. The westernized diet typically includes
increased consumption of animal products, fat (especially saturated
animal-derived fat and vegetable oils), sugar, ultra-processed
foods/beverages, salt, and food additives.
The role of other hypotheses and mechanistic explanations could be
complementary to the role of the PHM or be related to the processes that
stem from the effects of the PHM.