From Gut to Brain: The Inflammation Connection

Gut to Brain

When a woman experiences fatigue, brain clouding, flat mood, PMS, and/or constipation, we call it a result of anxiety or stress, then we stick her on an antidepressant that she will likely take for the rest of her life. Where in this protocol have we investigated why she is feeling that way? How have we personalized the treatment to her unique biochemistry? How have we developed a plan to deal with side effects, including new and different psychiatric symptoms resulting from this prescription? We haven’t. We’ve applied a one-size-fits-all treatment to mask symptoms without considering the cause, and the real cause may be a hidden condition known as inflammation.


Psychiatry has known about the role of the immune system in certain presentations of depression for the better part of the last century. More recently, the role of altered immune set points and inflammation in models of depression has been explored. The immune system is largely housed in the gut—and the interplay between the gut and the brain is a complex and profoundly important relationship to appreciate.

We all recognize that anxiety or nervousness can impact the gut—most of us have had butterflies before a date, or even diarrhea and extreme performance anxiety. We are just learning, however, that this relationship is bidirectional; the gut can also communicate its state of calm or alarm to the nervous system. It’s probable that the vagus nerve—a specific nerve within the brain that helps control the heart and digestive tract—is a primary conduit of information and that inflammatory markers are the vehicles traveling this highway. Scientists have studied the “protective effects” of severing this nerve when animals are exposed to gut-related toxins that normally cause depressive symptoms. We are getting ahead of ourselves, however, because we need to better elucidate why inflammation matters, where it comes from, and why it is the universal driver of chronic illness.


When a woman feels foggy, run-down, easily overwhelmed, and flat, we know that her hormones—as messengers between her gut and brain—are out of balance. This hormone derailment may be a downstream effect of cellular dysfunction resulting from oxidative stress and inflammation. Inflammation stems from many sources, including the following hallmarks of the modern American lifestyle.

>>Sugar Particularly in the form of fructose and sucrose, sugar spikes insulin and triggers the release of inflammatory cytokines. It forms advanced glycation end products (AGEs) when it binds to proteins, and it oxidizes lipids, which form cell and mitochondrial membranes.

>>Chemicals Pesticides, environmental pollution from industrial waste, hormonally modulating plastics, fire retardants, and cosmetic additives all stimulate our immune systems to varying extents and disrupt optimal production of energy on a cellular level, particularly in vulnerable tissues such as the thyroid.

>>Pathogens The aforementioned culprits, and others such as herbicides, gluten grains, and genetically modified foods, promote intestinal permeability—effectively changing our intestinal flora and facilitating the growth of pathogenic bacteria, yeast, and fungus, thus keeping our immune systems in a state of alarm.

>>Stress This catch-all term represents the ultimate link between hormones and inflammation because stress—either psychological or physiological—triggers the release of cortisol. Cortisol helps to mobilize blood sugar so that you can respond effectively and efficiently to imminent threats—i.e., cortisol propels us into “fight-or-flight” mode. It also acts as a systemic immune suppressant, lowering levels of secretory IgA, an important body guard of the gut mucus membranes.

Cortisol and insulin are like stress-response sisters, and high cortisol states will also contribute to insulin resistance—a state of high insulin and high sugar levels—while the cells themselves starve. Insulin protects fat storage (inhibits lypolisis), and fat cells secrete their own inflammatory signals—in addition to converting testosterone to estrogen. This contributes to estrogen dominance, while also increasing the hormone DHEA and other androgens to fuel that process (as well as acne, hair growth, and agitation).

Cortisol also inhibits the conversion of stored thyroid hormones to active hormones, leading to states of hypothyroidism even with normal-looking lab results.

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Once inflammation is active, it is highly self-perpetuating. These inflammatory cytokines travel throughout the body, causing oxidative stress to the fragile machinery of our tissues and mitochondria. In the brain, inflammation serves to shunt the use of tryptophan toward the production of anxiety-provoking chemicals like quinolinate, instead of toward serotonin and melatonin.

Inflammatory cytokines produce a replicable collection of symptoms called “sickness syndrome,” which is noted for its overlap with “depressive” symptoms: lethargy; sleep disturbance; decreased social activity, mobility, libido, and learning; anorexia; and anhedonia, the inability to experience pleasure from activities usually found enjoyable, such as hobbies or music. Psychiatric researchers have observed that patients with higher levels of inflammatory markers (particularly C-reactive protein, or CRP) are less likely to respond to antidepressants yet more likely to respond to anti-inflammatories.


How is any of this good news? This approach to chronic illnesses such as depression views the illness as a complex, non-specific symptom reflecting a state of bodily disharmony. It isn’t that you were born with bad genes or low serotonin. It is far more likely that you are experiencing an unhealthy inflammatory balance, driven by cortisol dysfunction and stemming from a sick gut. You can come from many angles to modify your system, but here is a basic starter kit.

>>Exercise Burst exercise is my primary recommendation. It is the most bang for your buck in terms of cardiovascular benefit and specifically enhancing mitochondrial health. This type of exercise puts a special kind of stress on the body when you move to your max for 30 seconds, then recover for 90. I recommend eight sets of these two-minute intervals one to three times a week.

>>Meditation The effects of stimulating the relaxation nervous system, even by listening to a 20-minute guided meditation, can be far-reaching. One study demonstrated enhanced expression of anti-inflammatory genes and the suppression of inflammatory genes as a result of this type of meditation.

>>Diet I recommend a diet that controls glycemic fluctuations through the elimination of refined carbs and grains and the addition of high levels of natural fats to push the body to relearn how to use fats for fuel. This is the brain’s preferred source.

>>Strategic Supplementation Natural anti-inflammatories like polyunsaturated fats (e.g., evening primrose oil and fish oil), curcumin (the active component of turmeric), and probiotics, to name a few, can help promote a synergy of beneficial effects from the above interventions.

Despite some suggestion that antidepressants may actually be having their effect through an anti-inflammatory mechanism, these medications have become obsolete. An appreciation of the role of inflammation and immunity in driving hormonal imbalance—directly impacting mood, energy, and wellness—is at the core of personalizing the definition of “depression.” Don’t be lured into the simplicity of a one-disease, one-drug model. There’s no room for you in that equation.

By Kelly Brogan, MD

One Comment on “From Gut to Brain: The Inflammation Connection”

  1. Hi, I’m 21 and this issue has been one of my problem but thanks for this article, It’s a relief that I can do something about inflammatory. This is good! Double thumbs up!

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