For the first time in my 25 year career in psychiatry, there seems to be some agreement among Western medicine researchers and functional medicine practitioners about the role of leaky gut (also called gut dysbiosis or intestinal permeability) as the gateway for chronic inflammation and its effects on the entire body including psychiatric and mood disorders.
Here’s the story in a nutshell: “All disease begins in the gut”—Hippocrates made that statement almost 2500 years ago and it turns out that is still true but with a modern day twist. We think of classic inflammation as a short-term response to infection and injury that includes: pain, redness, heat, and swelling. Since 1993, we have used the term chronic inflammation to describe low-grade, persistent immune response that involves the entire body (not just local effects).
Our digestive tract is a vital immune barrier, protecting us from disease and contamination. Every day, thousands of microorganisms and by-products of digestion come into contact with this critical defense shield. The immune system in our gut (which accounts for 75-80 percent of our immune system) has to discern what is friend and what is foe. A healthy immune system is efficient in admitting the good and swiftly getting rid of the bad. But what happens when the gut gets overwhelmed by a mob—toxins in the environment, a nutrient deficient diet, stress, medications, and other factors? Defenses get weakened and the bad bacteria find their way in. Once that happens and toxic microbes spread throughout the body, the body’s inflammatory response starts attacking anything and everything. When that happens, you become at risk of developing a lifelong, debilitating autoimmune condition which might include: neurodegenerative disorders (Multiple Sclerosis, Parkinson’s Disease, Alzheimer’s Disease), psychiatric and mood disorders (anxiety, depression, ADHD), metabolic disorders (Type 1 and Type 2 Diabetes), intestinal disorders (celiac disease, irritable bowel syndrome, Crohn’s Disease, Ulcerative Colitis), various allergies and food sensitivities. Current research is confirming that leaky gut is a danger signal for autoimmune disease.
But Why Is This Happening?
We believe this is happening more due to environmental changes that have increased the disease liability of genetic profiles that were previously benign and that it all the starts in the gut. These environmental factors are converging at once and include:
The corruption of the food supply: it’s not just the obvious junk food offenders like McDonalds but many of the packaged foods on supermarket shelves labeled as “healthy” contain various ingredients and additives that do our gut harm. The list includes sugar, salt, gluten (includes wheat, rye spelt, barley), vegetable oils, cow’s milk. Modern day wheat has been hybridized over the past 50 years, sprayed with massive amounts of chemical fertilizers and pesticides, promotes unstable blood sugar and is likely a major culprit in the U.S.’s obesity epidemic.
The rise of environmental toxins: this includes pesticides, herbicides, and fungicides that leave behind a toxic chemical residue on produce that taxes the liver and the digestive system. Industrial cleaners used in the home as well as the personal care products applied to our skin also add to the body’s toxic load.
The overwhelming stress of modern life: I think we can all agree that stress makes us sick, wears us out emotionally, and can exacerbate any health condition you can think of. Researchers have found that mental stress can alter the bacterial composition of the gut, favoring “nervous” strains of bugs leading to higher rates of leaky gut.
Unrelenting germ warfare: the American obsession with personal hygiene including daily showers with soap and shampoo damages the outermost protective layer of the skin and disrupts the delicate balance maintained by the bacterial ecosystem that inhabits our skin.
Medications: major culprits include antibiotics, NSAIDs (Advil, Aleve), and proton pump inhibitors (Prilosec, Prevacid) by damaging the intestinal lining and diminishing or depleting vitamins, nutrients, and beneficial microbes.
Other triggers: lack of sleep, infection, hormonal imbalance, urbanicity
Inflammation in Depression: Does this mean that we now believe chronic inflammation causes depression? It would be great if that turned out to be true for everyone by simply reversing all the above listed factors but of course nothing is ever simple and the one size fits all model doesn’t work in this case either. The research suggests that inflammation is a subtype of depression but still a significant one. High inflammation does biologically correlate with atypical depression but not common depression. The biological correlate in this case is CRP (C reactive protein), a marker of systemic inflammation, which can be measured in anyone with a simple blood test. CRP is elevated (>1 mg/L) in atypical but not non-atypical depression. Research is starting to show that patients with an elevated CRP, indicative of high levels of inflammation, are more likely to respond to a noradrenergic antidepressant (like nortriptyline or Wellbutrin) than with a serotonergic agent (SSRI like Lexapro).
Atypical depression is a bit of a misnomer as it’s not atypical at all and can account for 40-45% individuals with Major Depression. It’s also twice as common in women than in men and can be associated with obesity, diabetes, metabolic syndrome and a history of trauma. Other features include: reactivity of mood, increased appetite, more sensitivity to rejection, increased sleep, fatigue, and a sense that one’s limbs are weighed down and heavy. Reactivity of mood implies that individuals experience improved mood when encountering pleasurable events which does not typically occur in common depression.
Is it possible that individuals with Major Depression that have an inflammatory cause (atypical features) can reverse their symptoms through lifestyle changes? I believe the answer in some cases is yes and I’ve seen it first hand in my own clinical work. Here’s the catch: most people are not motivated to make these lifestyle changes especially if they are feeling depressed. As a physician, I feel it’s important to address root cause factors but in the end it’s not up to me what people decide. However, sometimes it’s easier to motivate someone by treating the depression first with medication in the short term but use the medication as a tool for transformation and a motivator to go back and make the necessary lifestyle changes.
The take home point of this article is to consider asking your physician (it doesn’t have to be a psychiatrist) to order a CRP the next time you need blood work which is a blood marker of inflammation (eg. CRP<1 mg/L, low inflammation, 1-3 mg/L, moderate inflammation, >3 mg/L, high inflammation). If the results are >1 mgl/L, I would strongly recommend employing anti-inflammatory lifestyle changes whether you are depressed or not. I will highlight what these lifestyle modifications would look like in Part II of this article so stay tuned.