The human immune response system, much like that of other mammals, evolved over hundreds of thousands of years to be a barrier against the nasty bugs and pathogens we live with day-to-day. Since the discovery of antibiotics (and their overuse in both human medicine and industrial farming), we have created a very clean and sterile environment. But is it too sterile? From improvements in sanitation, the processing of food, and filtering of water, we have, for the most part, removed the everyday pathogens our ancestors had to deal with. And while few can argue this has not been a great benefit to longevity and human health overall, there are a few hitches. One of which is the increase in autoimmune disease.
Like other mammals and in fact most vertebrates, the immune function is a complex system that uses some organs, glands, tissues, and even microbiome (the bacteria that live within our bodies) to defend against invading pathogens. It is a robust system, designed by biological evolution to protect us from the nasty bits of the environment. In the past few hundred years, our immune systems have remained mostly unchanged, while industrialization has cleaned up our act to the point of near sterility. Even the slightest infection has us in the physician’s office, and the bug is quickly overwhelmed by antibiotics; public health has removed many of the routes that disease once used to infect us, such as contaminated water, sewage, etc. Interestingly enough, the infectious disease only became a significant threat to human health with settled agriculture and the settling of populations near each other. In the meantime, this fantastic system of tissues, organs, and beneficial bacteria is waging war against pathogens that are no longer a threat. But what if the immune system, long evolving to protect us against changing nemeses, suddenly finds itself without enemies to fight?
In ancient Rome, the army was kept busy expanding the frontier. Not because Rome needed to grow, but because a large army, not kept occupied and is likely to become a threat. Often the same scenario plays out in our bodies, as our immune response, finding no invaders, can occasionally begin to attack our tissues and organs resulting in autoimmune conditions like Asthma, Lupus, Diabetes, Rheumatoid Arthritis, Irritable Bowel Syndrome, Addison’s Disease, Grave’s Disease, Hashimoto’s Thyroiditis, and Celiac Disease are known to be, or are suspected to be, rooted in evolutionary mismatch.
Immunologists and epidemiologists investigating the rise in autoimmune conditions have coined the term hygiene hypothesis, and there seems to be a strong association with the significant changes in Westernized civilization over the past 150 years. When medical scientists began investigating the differences in infectious and chronic diseases in the past century through examining medical writing, and more recently through medical data collection, the increases in allergies, autoimmune disease, and inflammatory conditions like cardiovascular disease, atherosclerosis, and metabolic syndrome may be the result, at least in part, to non-exposure to the natural world. Life in an overly-sterilized environment and the resulting reduction of the native microbiota through the overprescribing of antibiotics, the use of antibiotics in industrial farming may be at least partly responsible for the sharp increase in autoimmune conditions in the West.
According to the hygiene hypothesis, the drastic increase in allergies, autoimmune diseases, and inflammatory conditions may be related to the reduced exposure of our immune system to antigens it has long evolved strategies to overcome.
We would expect a rise in inflammatory disease (chronic conditions) in industrialized countries with large urban areas and where the common infections our ancestors had to survive have been removed mainly through some public health actions, including clean water through chlorination, improved sanitation, and a significant reduction in once deadly infectious disease. And while these improvements have been ongoing for 150 years or more, the most significant decrease in infectious disease has occurred since the discovery and use of antibiotics. Some researchers have postulated that by creating an overly sterilized environment, combined with crowded living (big city and urban community) mixed with food additives and chemicals designed to prevent spoilage, have so depleted the microbiota diversity in our gut, that the drastic increase in inflammatory disease is not only understandable but predictable.
If you were to total the number of cells in the human body, roughly speaking, they would total approximately 90 billion. And of that 90 billion, less than 10 billion would have your DNA. By far the majority of the cells within us are comprised of symbiotic life forms that have created a community that benefits our digestion, our organ systems, and our immune response. These communities have evolved with us over the past 80,000 or so years, with one single aim: homeostasis. When we disrupt this community, through poor eating habits, we deplete this biome, and to a greater or lessor degree negatively impact these symbiotic organisms. The biome depletion theory is one way of understanding how the immune homeostasis has become disordered, and reactionary. This may help explain why antibiotic use in childhood often results in higher risk for asthma. However, many medical researchers and biological scientists could not agree with the hygiene hypothesis as it left too many questions unanswered. In 2003, Graham Rook, searching for a better explanation as to the drastic increase of allergic and immune response diseases among developing nations proposed that we had simply lost touch with “Old Friends” among the microscopic world.
These microscopic communities that makeup as much as 90% of our body mass have evolved along with our species and have existed since we were primarily hunter-gatherers and have evolved along with our immune system. According to Rook, the vital microbes that have been present throughout nearly all of human history have become depleted through poor diet and overly sanitized environments leaving at least some humans prone to poor immune response, while others may suffer from over-response in the form of autoimmune disorders. Rook and others have proposed that the microbes found in the natural environment evolved an ambient, coexistence with humans, and various species of bacteria that naturally and habit the skin, respiratory track, and digestive system of humans have historically acted as alarms for our active immune system. Various organisms, from viruses to helminths, these organisms reside in humans naturally, in what has been described as a neutral or carrier state that is tolerated by the human immune system. Many of these neutral or carrier state microbes include those found in soil and water (mycobacteria), and throughout much of human history have acted as an internal testing ground for our immune function. Many argue that these organisms are necessary to create a strong immune system.
Other pathogens cause responses in specific immune cells, for example, T-helper type 1 in response to salmonella, which is also effective at destroying many other pathogens. Many researchers argue that exposure to these microbes prompted a healthy immune function and that exposures during early life may be associated with not only physical health but psychological health as well. The deficiency or lack of exposure to these “old friends” leads to a weekend or defective immune regulation, and it is argued that the absence of these microbes which evolved alongside (and inside of) humans for tens of thousands of years may be at the root of the drastic increases in allergy and autoimmune disease.
Over 90% of all human evolution is thought to have occurred in small, isolated hunter-gatherer groups. These groups routinely moved through the natural environments, coming into contact with other species both large and small. Given the availability of pathogens, viruses, bacteria, and parasites in the natural environment, the human immune system became robust and relied on the presence of microbial exposure to maintain the immune response. These microbes created a reciprocal relationship where their presence was largely overlooked because they stimulated immune responses to allergens and infection.
Given that the majority of humanity no longer lives in hunter-gatherer groups, but in large population centers where the natural environment is almost entirely absent, and we have little if any exposure to the old friends of evolution, what can we do to increase our resistance to infection, inflammation, or autoimmune conditions?
Part three: Energy balance, homeostasis, and couch potatoes.