Whether we are discussing cardiovascular disease, metabolic disorders, autoimmune conditions, or even chronic digestive issues like IBD, patients share a common desire: to know the root cause.
For decades, we often looked for a single culprit, a specific gene or a singular bad habit. However, modern research confirms that the vast majority of chronic diseases are too complex for a single explanation. They are the result of a powerful, continuous interaction between three core pillars of health: Genetics (G), External Environment (E), and the Microbiome (M).
I call this universal framework the GEM Triad. Understanding your personal GEM factors is the key to moving past symptom management and achieving true, lasting health.
The way I look at it is that diseases may have components of each of the GEM triad but at different proportions. For example, when the Covid pandemic happened, I saw variety of manifestions. I have seen older frail patients who came to the hospital with diarrhea and not much other symptoms and then I took care of healthy young marines who were intubated in the ICU and some of them ultimately died. What could explain such spectrum of manifestions at an individual levels. We clearly realized the frail, obese, diabetic and the elderly were at higher risk but at as an individual who is affected, statistics do not mean a thing.
Now we are dealing with increasing risk of colorectal cancer in the younger population. This clearly is not genetic but we focus our attention on the genetic basis of cancer. Is it only the “ E” component or it’s “G”? May be it’s microbial. Maybe it’s microbial due to altered microbiome due to several factors including consumption of too many take outs. I believe for all disease states we should explore and explain from the GEM model of disease causation.
I do not think Alzheimer’s is all genetic. We are so focused on pathways that we can interrupt with a pharmaceutical to restore health but what if the center of declining brain health lies somewhere else? Like the gut? Or the microbes? Or what we put in our mouths?
Unifying Disease: The Three Pillars of the GEM Triad
The GEM Triad provides a comprehensive lens through which we can view the mechanisms behind illnesses like Type 2 Diabetes, Arthritis, Alzheimer’s, and heart disease.
G: Genetics – The Host Blueprint of Susceptibility 🧬
Your Genetics (G) represent the innate host factors, the inherited blueprint that determines your susceptibility. Genes do not typically sentence you to illness, but they create the vulnerability or potential for disease.
Our genetics has a huge influence on the microbial load we carry. Based upon our genetics our body will host or not host certain microbial groups and then these microbes alter our genetic expression. It’s a two way street. More about that in the microbial section.
- Immune Propensity: Your genes dictate how easily your immune system might become confused or overactive.
- Metabolic Efficiency: Genetic variants influence how you process sugar, store fat, or clear toxins.
- Analogy: The G pillar is The Loaded Gun. It establishes the baseline risk, which we must respect and monitor.
E: External Environment – The Triggers and Modulators 🧪
The External Environment (E) encompasses all extrinsic factors that you encounter daily. These are the powerful forces that directly trigger genetic susceptibilities and reshape your microbial landscape.
The E pillar includes crucial factors like:
- Lifestyle: Chronic stress, lack of physical activity, poor sleep, smoking, consumption of things that we doctors tell you not to or doing in moderation.
- Nutrition: A diet low in nutrient density or high in inflammatory compounds (e.g., highly processed foods). Our food industry has done us a huge disservice by catering to our basic survival instincts and providing us with hyperpalatable foods. I cannot think of any hyperpalatable food which is good for you. What makes the food hyperpalatable? Fat, sugar and salt. Then we have spate of foods with health claims. That superfood and this adaptogen. Now there is a rage of Non GMO, Organic, Vegan, no seed oils etc. Simple things are often the best. Minimally processed foods, eat less than what you can, go to bed relatively hungry, don’t get intoxicated, work out before life gets you busy, cultivate good relationships and remember consuming too much protein while not working out does you no good.
- Exposures: Toxins, pollution, or necessary medical interventions like antibiotics. Unfortunately, they have become ubiquitous. You breath them in, found in foods containers and wrappers, your receipt from the gas station and even in water. We exchanged pathogens in our foods for toxins. One has immediate consequence and the other is delayed.
M: Microbiome – The Microbial Mediators 🦠
The Microbiome (M)—the vast, dynamic community of bacteria, viruses, and fungi in your gut—is the revolutionary third pillar. It acts as the central mediator between your genes and your environment. My astute patients point out that we should consider microbiome as a part of the external environment. I do not think there is a black and white answer to it. We, without the microbiome that live on and in us won’t survive very long. In fact, there are more microbes on and in us than we have cells. I divide the interaction between ourselves and the microbes into these four categories.
1. Transients: These microbes were on your salad. They come and go. They do not have any permanent home in our body.
2. Commensals: Means sharing the same table. You get the meaning.
3. Symbionts: They help us and we help them. e.g folic acid production in our gut. Symbiotic organisms can be commensals and majority of them are mutualistic.
4: Pathogens: Traveler’s diarrhea. Need I explain more? There are far more dramatic examples.
Every external factor (E) you consume or encounter instantly communicates with your microbiome (M) and your hormonal system. In turn, these microbes communicate with your immune system (G). Your hormonal system includes the insulin, glucagon, ghrelins, leptins as well dopamine your happiness hormone. To make matters simple, I will be discussing our microbes, hormones are another chapter .
There are a vast number of probiotics, synbiotics available in the market at various price points but how do you know which one is going to work for you? I have no idea. No one has any concrete idea. We think it may work but randomized controlled trials and long term data is lacking. So, majority of probiotics have claims that have not been substantiated in a large study and if you were look into the guidelines of our GI societies, the recommendations are very limited and conditional and the preface by saying that the quality of evidence is low to moderate.
- Inflammation Control: The M-pillar trains your immune system and determines the levels of inflammation-controlling compounds released into your bloodstream. We have circumstantial evidence on this but the question I ask is how are we measuring inflammation? We surely know that early infanthood is crucial in forming sturdy gut and systemic adaptive immunity and early exposure to antibiotics, lack of breast feeding, delivery by caesarean section may have deleterious effect.
- Disease Mechanisms: When the environment (E) leads to microbial imbalance (dysbiosis), the microbes may signal the immune system to attack self-tissue in a genetically susceptible host (G)—a mechanism key to autoimmunity and chronic inflammation. We are still in the process of learning and understanding what is normal and abnormal or to even define what is dysbiosis for an individual. Is it dysbiosis if one has no symptom, does it portend future problem? We have inklings, but no real idea on how to remedy it. Each body part or organ system may have a different definition of normal and abnormal. What is normal for a person in a particular stage in life or geographical location may not be normal in a different phase in life. Did you know that some of the markers of Inflammatory Bowel Diseases that we test for are actual antibodies to body parts of various bacteria and yeast?
Health Through the GEM Lens
We talk about personalized health, it’s all good in theory but the most practical intervention that will result in immediate improvement in your health would be doing simpler things first. Let’s start by reducing the amount of restaurant foods and takeouts we eat. Only you have your health as your primary concern, the businesses do not. It’s their bottom line. Saturated fat is not good for you despite all the health gurus proclaiming to go off seed oils and eat more beef fat. Just ask them to show a large study. There always be anecdotes that goes against the guidelines but that cannot be followed blindly. If you have your genetic data upload it to promethease and it will give you recommendations based upon your profile.
- We manage G by tailoring treatments based on known genetic susceptibilities.
- Restoration of our Microbiome: Challenging. There are several companies offering to check your gut microbiome. We do not recommend doing it as what’s in stool is different from what lives in our gut lining. We do not have a reliable method to shift the balance. The best we can do it consume whole plant based diet and limit super tasty processed foods.
- We optimize E by creating sustainable lifestyle plans focused on stress reduction, toxin avoidance, and healthy habits.