Today we’re facing the most serious epidemic of chronic diseases as a human species with half of all US adults diagnosed with at least one chronic health condition. Most patients who have conditions such as irritable bowel syndrome (IBS), chronic fatigue, fibromyalgia, and autoimmune disease are told that the cause of their condition is unknown and are then prescribed drugs to simply manage the symptoms. In reality, we do understand the most important factors that fundamentally contribute to all chronic disease which means we can prevent and even reverse many of these conditions. Read about Dr. Chris Kresser’s Functional Medicine Systems Model and The 8 core pathologies that underlie all chronic disease, below.
Functional Medicine Systems Model
As the diagram illustrates, the interaction between an individual’s genome, epigenome, and exposome is at the core of what determines our health.
The genome is our complete set of DNA, containing all of the information needed to build and maintain the human organism.
The epigenome consists of chemicals that modify the genome in a way that tells it what to do, where to do it, and when to do it. These modifications do not change the underlying genes, but they can be passed on to future generations.
The exposome represents the sum total of all non-genetic exposures an individual experiences from the moment of their conception through the end of their life. It includes the food we eat, the water we drink, the air we breathe, the chemicals we’re exposed to, the social connections we have, and the environment we live in.
To use an analogy, the genome is like a piano; the epigenome is like the sheet music; and the exposome is what determines how the music is written and performed. The quality of the piano will certainly affect the sound that it produces. But the finest piano in the world will still sound terrible if the sheet music and performance are terrible. Likewise, a virtuoso pianist performing a Mozart piece will not be at her best playing a poor-quality piano.
In the same way, genetics do play an important role in human health and disease. However, we now know that the exposome (and its influence on the epigenome) is far more significant in most cases. In fact, it is responsible for >90% of human disease. That is why the exposome is at the core of the Functional Medicine Systems Model, and should always be the first thing addressed regardless of the patient’s complaint.
The modern diet, lifestyle, and environment affect the expression of our genes and lead to pathology, which in turn cause disease and symptoms in the patient.
But what are those pathologies?
The 8 core pathologies that underlie all chronic disease
I believe that virtually all diseases and symptoms that we experience are caused by one or more of the following 8 core pathologies:
Gut dysfunction. Includes small intestine bacterial overgrowth (SIBO), infections (e.g. parasites, pathogenic bacteria, viruses), low stomach acid, bile, and enzyme production, intestinal permeability, and food intolerances.
Nutrient imbalance. Includes deficiency of nutrients like B12, iron, folate, magnesium, zinc, EPA/DHA and fat-soluble vitamins (most common), and excess of nutrients like iron (less common).
HPA axis dysregulation. Includes regulating the communication between the hypothalamus, pituitary, and adrenal glands, and balancing the production of hormones associated with those glands (e.g. DHEA, cortisol)
Toxic burden. Includes exposure to chemicals (e.g. BPA, phthalates, etc.), heavy metals (e.g. mercury, arsenic), biotoxins (e.g. mold/mycotoxins, inflamm), or impaired detoxification capacity due to nutrient deficiency, GI issues, or other causes.
Chronic infections. Includes “stealth” infections by tick-borne organisms (e.g. Borrelia, Babesia, Bartonella, Erlichia), intracellular bacteria (e.g. Mycoplamsa, Chlamydophila), viruses (e.g. HHV-6, HPV), and dental bacteria.
Hormone imbalance. Includes hormones associated metabolism (e.g. insulin, leptin), thyroid, and gonads (e.g. estrogen, progesterone, testosterone).
Immune dysregulation. Includes autoimmunity, underactive immune function, and chronic, systemic inflammation.
Cellular dysfunction. Impaired methylation, energy production, and mitochondrial function, and oxidative damage.
These pathologies (and the exposome-genome-epigenome interactions that lead to them) are at the root of everything from obesity, to Hashimoto’s thyroiditis, to asthma, to autism spectrum disorders, to depression. The understanding that the same 8 core pathologies underlie most modern, chronic diseases has profound implications for how we should address these conditions.
In conventional medicine, the focus is often on diseases and the symptoms; it works “from the outside in”. For example, let’s say that you go to the doctor for your annual exam and your blood tests reveal that you have “high cholesterol”. The most likely outcome in this situation is that you’ll be prescribed a statin, and in some cases be told to exercise more and eat better. There is rarely any serious investigation into what caused the high cholesterol in the first place.
In functional medicine, however, we work “from the inside out”. We pay less attention to the symptoms, and more attention to the pathology that produces those symptoms. High cholesterol is a symptom, not a pathology. The pathologies that can lead to high cholesterol include poor thyroid function, intestinal permeability, disrupted gut microbiome, chronic viral or bacterial infections, insulin and leptin resistance, and nutrient imbalances—to name a few. If I find high cholesterol in a patient, we will examine all of these potential pathologies, and of course we will also look at how the individual’s genetics, diet, lifestyle, and other factors related to the exposome may be contributing to them. Once we have addressed all of the core pathologies, the cholesterol levels typically normalize on their own.