Inflammation: The Root Cause of Chronic Disease?

hand-drugsYour immune system is magnificent. It has been shaped over eons of time in response to environmental pressures. We humans no longer have to compete with other animals for food or escape large predators that lurk in the wild, but that doesn’t mean our struggle for existence is over. We still have to change in order to survive, in part because we have to keep up with the rapid Darwinian evolution that goes on in the microbial world around us. Some of these adaptive changes occur in our own genome, such as through the positive selection of traits that confer an increased protection against certain pathogens, while others occur in the microbial part of our body.

In many developing countries, infectious diseases are a huge problem, and millions of people die every year because they don’t receive the vaccines and medications their immunocompromised bodies need to fight off harmful invaders. In the developed, industrialized world, the number of deaths attributable to microbial infections are more modest; however, that doesn’t mean our immune systems can sit back and relax. On the contrary, the immune system of the modern man is constantly dealing with stimuli that bring about a perturbation of homeostasis. 

What happens when the fire never stops burning?

Inflammation is the body’s natural response to injuries and infections. In this sense inflammation is a good thing. Our bodies are supposed to react when we get injured or encounter substances that appear foreign and harmful. Through the activation and production of immune cells and cytokines, the body attempts to rectify and normalize the situation.

The problem occurs when inflammation goes from being acute to chronic, which is what has happened in the body of many modern people. The human body is well-adapted to deal with acute inflammation, which is what occurs when we get a wound or sprain our ankle; however, it doesn’t do so well when there’s an unresolved inflammatory process going on. Instead of allocating resources and energy to systems that we depend on for optimal fitness and virility, it focuses on cleaning up the mess.

As I’ve mentioned in many of my previous articles on this topic, it’s well established that chronic low-grade inflammation is at the root of many, if not most, of the chronic diseases and health disorders that plague us in modern societies, including type-2 diabetes, cardiovascular disease, and depression (1, 2, 3, 4, 5).

What has become increasingly clear to me over the years is that chronic low-level inflammation is a condition that can both be seen and felt. You don’t have to check the levels of C-reactive protein, interleukin-6, or tumor necrosis factor-alpha in your bloodstream to know whether there’s a “fire” burning within you, you can simply do an assessment of your current health condition. If you are very overweight, have low libido, feel chronically fatigued, experience muscle weakness, and/or get acne, then the levels of inflammatory cytokines in your body are probably elevated beyond a healthy niveau. Even if you don’t suffer from any of these problems, chances are you are still somewhat compromised, as it is almost impossible to maintain truly great health in the evolutionarily abnormal environment we’ve created for ourselves.

Prescription meds won’t get you very far

What does this mean? Should you run to your doctor and get a prescription for some anti-inflammatory drugs? No, unfortunately, your doctor most likely won’t have any solutions to offer you. The reason being that conventional medical training and mainstream medicine largely focus on the molecular and physiological mechanisms underlying health and disease, while paying little attention to evolutionary theory and the question of why diseases arise in the first place.

The inflammation that is brewing within the body of the modern man doesn’t arise from a single cause or dysfunction that can be removed with a drug or surgery, but rather from a combination of factors that induce hormonal dysregulation, gut leakiness, loss of microbiota diversity, and abnormal gene expression patterns. In the modern world, most of us subject our bodies to stimuli that fall in the category of being too much (e.g., sugar intake), too little (e.g., sleep), or too new (e.g., cigarette smoke), when compared to what our bodies are adapted for. By addressing this problem, we can return our bodies to a state that is closer to the evolutionary norm for Homo sapiens sapiens.

If you’ve been following for some time, you’ve probably noticed that I talk a lot about evolutionary mismatches, chronic inflammation, gene expression, and the human microbiome here on the site. This is not by coincidence. It is my belief that these four things are key to understanding why we get sick. Evolutionary mismatches lead to perturbations of the human microbiome and abnormal gene expression, which then leads to chronic inflammation, poor health, and chronic disease.

This simple model can help guide our understanding of health & medicine. That said, there are of course other factors involved and a lot of details that need to be included to get a good understanding of what’s going on. Also, perhaps needless to say, not all of the diseases and health disorders can be explained using this model.

The completed self

I’ve taken an in-depth look at the causes of chronic inflammation in many of my previous articles, as well as discussed what we can do to reduce inflammation (Hints: Take better care of your microbiome, adhere to a Paleo-style diet), so that’s not something I’m going to do again here. Rather, I thought I would finish off today’s relatively short piece with a quote and figure from a paper I read recently entitled The Completed Self: An Immunological View of the Human-Microbiome Superorganism and Risk of Chronic Diseases. The authors of this article make the case that misregulated inflammation driven by altered epigenetic programming, developmental immunotoxicity, and altered neonatal microbial colonization is a key biomarker connecting a majority of chronic diseases.

Early life interactions that disrupt formation of the Completed Self [The human superorganism, including both mammalian and microbial cells] are suggested to be as a primary contributor to misregulated inflammation and risk of later-life chronic diseases. Reported comorbidities among selected chronic diseases and conditions are shown in this figure and are represented by the interconnecting lines among diseases. These comorbidities are extensive illustrating the extent to which much of human disease is interconnected and promoted by misregulated inflammation. For example, tissue-specific cancer is a later-life comorbidity of asthma (lung cancer), inflammatory bowel disease (gastrointestinal cancer) and psoriasis (skin cancer). Cardiovascular disease (e.g., atherosclerosis), depression, and frailty are common later-life comobidities. It is suggested that environmental interference with human superorganism formation corrupts a biological sign for later-life health. (1)



  1. Alessio says:

    Very well said! All we can do is trying to follow a paleo template and lifestyle as much as possible trying to do the “less worse” we can do in our rotten environment.
    We’ll never go back like we were born among Hadza, but at least it would still be a farcry from the average sick obese Joe…

  2. Alessio says:

    I’m very disappointed when I hear people claiming:”you can’t eat and live like hunter gatherers, thus the paleo template is bogus”…it’s not a good excuse to do all the other way around, if you can’t do 100% so you do 0…
    Silly nonsense…


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  2. […] to show that a large proportion of the diseases of civilization, particularly those associated with chronic-low grade inflammation, are caused, in part, by a misfit between the human genome and the microbial environment, including […]

  3. […] it is a combination of genetic changes, reduced physical activity, increased dairy consumption, inflammation, and changes in the quality and composition of the human diet that has driven the increase in the […]

  4. […] compromised in some way, they certainly can be problematic. The immune system of the modern man is not in great shape, so there may be some room for concern […]

  5. […] what caused the observed effects, but the studies are clearly worth doing nonetheless. After all, chronic low-grade inflammation and the diseases of civilization are not caused by just one single factor, but rather, by many […]

  6. […] of years, unpleasant things happen: Our microbiomes and gene expression profiles change, we become inflamed and fatigued, and we lose our sex […]

  7. […] characterized by elevated levels of circulating inflammatory cytokines, a condition referred to as chronic low-grade inflammation. This inflammatory state is generally considered to arise as a result of obesity, due to the fact […]

  8. […] the immune system and the permeability of the intestinal barrier, something that affects the inflammatory status of the body, and hence, sensitivity to metabolic and adipostatic hormones, energy expenditure, and […]

  9. […] to defend itself is compromised. Most people in the world today house a degraded microbiota and have a slightly compromised immune system; hence, they are prone to attacks by […]

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  11. […] typically paying little attention to the root causes of illness. They may have heard or read that chronic inflammation is at the root of many health conditions, but since they have no medicines at their disposal that […]

  12. […] sleep than individuals who have chronically elevated levels of circulating inflammatory biomarkers (systemic, chronic low-grade inflammation), suffer from chronic disease, or otherwise are in bad shape. Keep in mind, I’m not just talking […]

  13. […] all chronic illnesses known to man have been linked with chronic inflammation. Inflammation tends to closely correlate with health (It’s a proxy for health). The […]

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  15. […] comment: Why is the human immune system designed the way it is? Why and how does inflammation cause disease? Why do so many contemporary humans develop chronic inflammatory diseases? The above […]

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