Genes Load the Gun, Epigenetics Pull the Trigger: A Bioregulatory View of Trait Expression

By Christine Dionese, Integrative Epigenetic Health Specialist

After twenty-five years in clinical practice working at the intersection of integrative epigenetics and psychoneuroimmunology through the lens of Bioregulatory Medicine, I've learned that the most important question is rarely "What gene do you have?" It is, instead, "What environment is that gene listening to?" The phrase "genes load the gun, epigenetics pull the trigger" endures because it communicates something both clinically accurate and profoundly empowering: genetic predisposition is real, but it is not synonymous with inevitability. The body is not a static machine executing a fixed program. It is an adaptive, self-regulating system responding moment by moment to information.

In a Bioregulatory Medicine framework, this is foundational. We are not simply treating symptoms or even isolated pathways. We are assessing regulation itself. How well does the organism maintain coherence in the face of inputs? How resilient is the terrain? How efficiently does it return to baseline after stress? How intelligently does it interpret signals—food, light, toxins, microbes, trauma, relationships, sleep, and meaning—and translate them into immune tone, endocrine rhythm, gut barrier integrity, and inflammatory setpoints?

Epigenetics is not an abstract concept in this context. It is the language through which the environment shapes physiology.

Epigenetic Expression Is the Sum of All Inputs, Not One Trigger

One of the most common oversimplifications I see is the idea that a trait expresses because of one "bad" thing. Gluten. Mold. Stress. A virus. A single nutrient deficiency. In reality, gene expression behaves far more like a voting system than a light switch. A single variable may matter, but it is rarely decisive on its own. Traits express when enough signals converge to push the system into a new adaptive state—one that may be protective in the short term, but inflammatory, symptomatic, or degenerative over time.

This is where psychoneuroimmunology becomes clinically indispensable. The immune system is not operating independently of the nervous system, and neither is independent of the endocrine system. Your threat perception, circadian rhythm, relational safety, and stress chemistry directly influence immune tolerance, gut permeability, inflammatory signaling, and the tendency toward auto-reactivity. When the organism lives in chronic sympathetic tone, the body becomes less discerning. It begins to interpret neutral inputs as threats. It becomes trigger-happy.

This is not philosophy. It is physiology.

Light exposure and latitude, sleep timing, indoor air quality, microbial diversity, dietary complexity, mineral sufficiency, hydration, movement, trauma load, social cohesion, endocrine disruptors, infections, and biotoxins all converge to determine whether a genetic vulnerability remains latent or becomes expressed.

Epigenetic expression is, quite literally, a real-time report card of the terrain.

Two Practices in NY & CA, Same Genes, Different Expression: A Clinical Pattern I've Seen Repeatedly: Southern Italian Genetics Across Sicily, New York, and Southern California

A vivid example of this appears in Southern Italian populations, particularly those with genetic variants associated with celiac risk or gluten sensitivity patterns. Many of these individuals carry the "loaded gun," so to speak, yet historically did not always express the trait clinically in Sicily. This is not because the genes weren't there. It's because the epigenetic context was different.

Traditional Sicilian living provided a set of regulatory supports that many modern environments quietly strip away. The sunlight was abundant and consistent, supporting immune modulation and circadian entrainment. The pace of life was often more physiologically compatible—less chronic urgency, less nervous system dysregulation. Meals tended to be anchored in real food, seasonal rhythm, and cultural continuity. Daily movement was integrated, not outsourced to the gym. Food preparation methods were traditional, slower, and more digestion-friendly. The microbial exposures of food, soil, and outdoor living shaped immune tolerance differently than sterile indoor modernity.

In that context, genetic predisposition could remain quiet.

When families migrated to the United States, however, the exposure landscape changed dramatically—and the epigenetic story changed with it. What has stood out to me in my own work is that even within the U.S., trait expression patterns diverged depending on where Southern Italian immigrants settled.

In New York, I observed a higher frequency of clinical expression in Sicilian-descended individuals who carried celiac-associated or gluten sensitivity-related predispositions. The pattern wasn't subtle: more inflammatory symptoms, more gut barrier compromise, more fatigue syndromes, more immune overactivation, and more auto-reactive tendencies that clustered around wheat exposure. Yet the more interesting truth was that wheat was rarely the true origin point. It was the visible spark in a system already saturated with invisible kindling.

New York brought high-latitude living with long stretches of reduced UV exposure and persistent cloud coverage, which impacts vitamin D signaling and circadian regulation. It brought a more indoor life, less morning light, more artificial light at night, and a greater tendency toward circadian disruption. It brought a stress ecology that is not merely psychological, but biological—more sympathetic activation, more cortisol dysregulation, and less parasympathetic restoration. It brought a food environment with more ultra-processed exposure and a higher frequency of industrial wheat products that are radically different from the traditional wheat experience many people imagine when they think "Mediterranean diet."

The outcome was predictable from a Bioregulatory perspective: a lowered threshold for immune tolerance and a higher likelihood of trait expression.

In Southern California, by contrast, many Sicilian-descended individuals appeared to maintain a more stable regulatory baseline. Again, not universally, but often enough to be clinically meaningful. The sunlight was consistent, supporting immune modulation and circadian anchoring. Outdoor living was easier year-round, and morning light exposure was more accessible. The climate, in many respects, resembled Sicily more than the Northeast did. This similarity matters. It is not a lifestyle preference; it is a biological input.

What I witnessed repeatedly was the same genetic predisposition expressing differently under different epigenetic conditions. The genes did not change. The environment did. And the body responded accordingly.

Why "Gluten Is the Problem" Is Often a Reductionist Conclusion

There is a reason gluten becomes the center of the story: it is a convenient villain. It is measurable. It is eliminable. And for many people, removing it provides relief. But relief is not the same as root cause.

In a Bioregulatory Medicine lens, the question is not only "Does this person react to wheat?" but "Why did this organism lose tolerance?" Loss of tolerance is not simply a food issue. It is a regulatory issue. It is an immune interpretation problem. It is often a breakdown in barrier integrity and immune discernment, driven by cumulative stressors that prime the system toward overreaction.

Modern wheat exposure is frequently accompanied by variables that the immune system reads as danger signals. Agricultural chemical load, pesticide residues, and herbicide exposure can contribute to gut barrier disruption and immune priming. Processing methods, reduced fermentation time, and the dominance of ultra-processed wheat products create a higher antigenic burden with less digestive support. High-frequency exposure without sufficient dietary diversity further narrows the immune system's tolerance bandwidth.

But wheat is rarely acting alone. Viral burden, mold exposure, heavy metals, endocrine disruption, mineral depletion, dysbiosis, and chronic stress can all push the immune system into a state where it reacts excessively to inputs that previously would have been tolerated. Once that threshold is crossed, wheat becomes a frequent target—not necessarily because it is uniquely toxic, but because it is ubiquitous, immunologically complex, and repeatedly encountered.

This is why I often say that "gluten sensitivity" can be a signal, not a sentence. It can be the immune system raising its hand and saying: regulation is compromised. The terrain is overloaded. The organism is no longer discerning.

Where Traditional Naturopathic and Functional Medicine Can Miss the Mark

I say this with respect for both fields, because I've worked alongside extraordinary clinicians in each and both are the basis of my early career, but there is a recurring limitation I see, and it matters if we want true outcomes rather than temporary symptom management.

Traditional naturopathic approaches can sometimes default to broad constitutional prescribing and gentle support without sufficiently addressing the modern intensity of immune dysregulation, toxicant load, and regulatory breakdown. The interventions may be "good," but not targeted enough for the terrain we are actually dealing with.

Functional medicine, on the other hand, often excels at identifying patterns and naming mechanisms, yet can become overly linear in execution. It can reduce complex bioregulatory problems into checklist medicine: remove gluten, heal the gut, treat the infection, replace the nutrient, retest. This approach can help, but it often misses the deeper hierarchy of regulation. It can treat the body as a collection of parts rather than a coherent adaptive system. It can chase markers without restoring true resilience.

Both models can unintentionally reinforce the idea that the problem is the thing being reacted to—gluten, dairy, histamine—rather than the state of the organism doing the reacting.

Bioregulatory Medicine asks a different question. It asks why regulation was lost, what level of the system is failing to adapt, and what inputs are preventing return to baseline. It prioritizes restoring coherence across the psychoneuroimmune axis, improving drainage and detoxification capacity, reducing immune hypervigilance, and rebuilding tolerance through terrain stabilization rather than endless avoidance.

The goal is not a lifetime of restriction. The goal is a body that can once again interpret the world accurately.

The Practical Implication: Epigenetics Is Not a Buzzword, It's Clinical Strategy

When I look at trait expression—celiac, gluten sensitivity, autoimmunity, inflammatory syndromes—I am never looking for a single culprit. I am looking at the total informational field surrounding the person. Light. Sleep. Stress chemistry. Microbial burden. Chemical burden. Food quality. Minerals. Relationships. Meaning. Movement. Trauma load. And the subtle ways these inputs shape immune tone.

The most important clinical shift is to stop treating genes like fate and stop treating symptoms like isolated failures. The body is always adapting. If we change the inputs, we change the expression.

Genes load the gun. Epigenetics pulls the trigger. But the environment decides whether the trigger is ever touched—and whether the organism is stable enough to keep the safety on.

If you want to change outcomes, you don't argue with the genes. You change the terrain.

A final layer that cannot be overstated is how easily an outdated perception can keep a person trapped inside the very biology they are trying to change. When the dominant narrative is "you have the gene, therefore you have the problem," the mind internalizes a kind of inevitability. That belief becomes a chronic signal to the nervous system that the body is vulnerable, defective, or one misstep away from breakdown. In psychoneuroimmunology, we understand that the nervous system does not distinguish between an actual threat and a perceived one. It responds to meaning. And when meaning is shaped by fear-based, deterministic thinking, the physiology follows.

This is one of the quiet failures of an overly mechanistic model of health: it can inadvertently turn a predisposition into an identity. People begin organizing their entire lives around avoidance, hypervigilance, and control. They become afraid of food, afraid of symptoms, afraid of stress, afraid of travel, afraid of normal life. And in doing so, they reinforce the very internal state that promotes immune overactivation, barrier fragility, and inflammatory reactivity. The terrain becomes narrower, not stronger. The person may become "more compliant," but less resilient.

This is why it matters who we entrust with our health. We need practitioners who are not simply practicing within the current paradigm, but helping shift it. Clinicians who understand that biology is adaptive and that regulation is trainable. Practitioners who can hold complexity without collapsing it into simplistic villains and rigid protocols. It takes a different level of leadership to guide someone out of symptom management and into true physiological restoration—where the goal is not perfection, but capacity.

A predisposition is just that: a predisposition. It is not a prophecy. But to live that truth, we have to stop relating to the body as if it is always about to betray us. The way we live our lives, the way we interpret sensations, the way we relate to uncertainty, and the way we construct meaning around our symptoms all shape the biological environment in which healing must occur. Epigenetics is not only about what we eat or what we avoid. It is also about the internal climate we generate through our perceptions and emotional patterns. The nervous system is upstream of almost everything.

When we create emotional safety—real safety, not performative positivity—we build the deepest kind of resilience. The immune system calms. The gut barrier stabilizes. Inflammatory thresholds rise. Hormonal rhythms normalize. The body becomes less reactive, more discerning, more capable of tolerating inputs without spiraling. This is not abstract. This is bioregulatory reality: a nervous system that feels safe is a nervous system that can repair.

And when the nervous system repairs, the terrain becomes fortified. Not rigid, not fragile, not dependent on constant control, but safe, secure, satisfied, and coherent. That is the terrain in which predispositions remain quiet, tolerance returns, and the body stops behaving as if the world is an emergency. This is where the epigenetic conversation changes—not because we found the perfect supplement or eliminated every exposure, but because we restored the organism's ability to interpret its environment with accuracy and respond with intelligence rather than alarm.

Bioregulatory medicine is a total body (and mind) approach to health and healing that aims to help facilitate and restore natural human biological processes. It is a proven, safe, gentle, highly effective, drugless, and side-effect-free medical model designed to naturally support the body to regulate, adapt, regenerate, and self-heal. BRMI is a non-commercial 501(c)(3) foundation and will expand and flourish with your support. Our goal is to make bioregulatory medicine a household term.

This article is for informational purposes only and is not intended to be a substitute for the direct care of a qualified health practitioner who oversees and provides unique and individualized care. The information provided here is to broaden our different perspectives and should not be construed as medical advice, diagnosis, or treatment.