Reader, I can’t remember a time when depression and mental health have been more central to our cultural consciousness. They have finally come out of the closet. Pop psychology is booming, celebrities are increasingly open about their mental health struggles, and even our television shows—from 13 Reasons Why to This is Us—offer intimate, and sometimes controversial, portraits of depression. And yet if you asked any of the patients I see on a regular basis, you’d see very quickly that the stigma of mental illness and depression is still very much alive. When someone has a persisting cough, it’s a no-brainer to make a doctor’s appointment to see what’s wrong. But when someone has persistent anxiety, chronic fatigue, emotional mood swings, or irritability, it often takes months, if not years of denial and delay before they visit a psychiatrist’s office to determine the root issue— if they visit at all. There are many reasons for the hesitation, but a primary reason I’ve witnessed is surprisingly simple and terribly sad: People still feel ashamed. They believe there is something defective about them, that they are damaged goods, and if they only had the will they could “fix themselves” and “be better;” or worse still, feel afraid that if they seek help they will be mocked by friends or loved ones.

Good Gut Bugs Treat Depression

For many patients, taking prescription medication that directly targets  their brain – where most of us believe our “personalities” arise—is a stigma within a stigma that can feel something like a personal affront. With all of this in mind, what if I told you that exciting new research suggests sometime in the not-too-distant-future, depression and other mental illnesses could be targeted and treated not in the brain… but in the gut? What if I told you that the 100 trillion bacteria that comprise your microbiome play a much larger role in your mental health and wellness than previously thought—and that treating them, rather than the “you” in your brain, may be a significant boon to recovery? If we as a culture believed our gut bacteria were to blame for our mental health outcomes, would the stigma of depression survive—or would the outsourcing of blame and shame from our brain to our bacteria turn the stigma on its head? These are exciting questions to consider—and today, I want us to consider them through the lens of Brenda’s story. Brenda felt shame at her own depression—but within months, she excitedly told me about her own mental illness, “It’s not me, Dr. Kehr—it’s my gut bugs!” If our gut bugs are the problem, reader, the answer to treating depression may very well lie in the simple administration of targeted probiotic bacterial strains. Let’s see how it all works!

Brenda’s Story: Depression is a Gut Feeling

At just 30 years old, Brenda* already held an impressive position in management at an Internet marketing firm. She joined the firm early on, which meant she’d accumulated stock in the company—and it was about to be acquired. To outsiders, it seemed Brenda was guided by a lucky star: at an age where most of her peers are just beginning to truly build their careers and think seriously about saving, Brenda had already reached an incredible peak in her professional life—and she had an equally impressive nest egg to show for it. Yet these were not the first details I learned about Brenda—far from it, in fact. Instead, Brenda stepped into my office with a distraught expression and spoke with an urgency so strong I could practically feel the pressure and stress emanating from her as she spoke familiar words “Dr. Kehr, something is wrong with me. At times it feels like I’m dead inside, like I’ve been transformed into a zombie!” As she described episodes of emotional escalation, anger outbursts, binge eating, suicidal thoughts, mood swings, irritability, long periods of remaining in bed, and fatigue, her face took on an expression of tearfulness and near embarrassment. Self-consciously, she moved on to tell me of her physical symptoms as well: stomach pains, heartburn, acid reflux, belching, a grumbling stomach, and urgent bowel movements. She was also about 20 pounds overweight.

Brenda’s mental health concerns were thus twofold: she had symptoms impacting her mood and behaviors, and she had symptoms impacting her physical health. Brenda’s mood symptoms dated back to childhood, and since then she’d been treated with stimulants for ADHD as well as lithium, all to no avail. Her family history was positive for bipolar disorder in an uncle, and her mother suffered from depression. I diagnosed Brenda with rapid cycling bipolar disorder and probable dysbiosis. We performed Genomind’s Professional PGx Express Assay on her, which revealed COMT Val/Val, ADRA2A C/C, MC4R A/A, and CACNA1C G/A. These variants pointed toward increased rates of dopamine breakdown, likely poor response to stimulants, difficulty feeling full (poor satiety signaling), and a higher likelihood of mood instability. We also performed a blood test which revealed low estrogen, low vitamin D and elevated inflammatory biomarkers.

Administering a genetic test revealed important indicators about Brenda’s mental health. To bring about the fastest possible symptom relief, I began her on Memantine to address her calcium channel variant and unstable moods. But we also urgently needed to treat Brenda’s physical symptoms of dysbiosis. Her microbiome was most likely causing her digestive system issues —but I knew it was very likely the dysbiosis itself was serving to underscore or possibly even perpetuate her depressive symptoms. We ordered a stool test to examine my hypothesis.

Depression and Your Microbiome

Microbiome transplantation accounts for some of the most exciting research about our gut bacteria—and transplantation observations have revealed incredible insights about how and where depression manifests itself in the body. Scientists have found fecal microbial transplantations (FMT) from a human suffering Major Depressive Disorder into a microbiome-free rodent causes it to develop depression-like symptoms, from anxiety-like behaviors to anhedonia, or the inability to experience pleasure or excitement. Given that depression has long been thought to be a brain-centered illness, it’s incredible to think that our gut bacteria—species that do not even qualify as genetically “us”—could play such a significant role in causing mental illness. Let’s take a look at just a few of the ways this may be possible (and for more information, I highly recommend this research article that outlines each of the categories below):

The Gut-Brain Connection: First and foremost, we must recall from a prior blog the significant communication that occurs between the brain and the gut. Study after study has shown that a dysregulated microbiome can lead to significant consequences in the brain and body—so let’s keep in mind this intricate and important connection as we move on to a few other causes of depression in the gut:

Bacterial Metabolism: As we discussed last week, our bacteria love snacking on prebiotics, or indigestible carbs. Our bugs can then transform those snacks into short chain fatty acids, or SCFAs, which can cross the blood barrier and move to all different parts of our bodies to send messages that inhibit inflammation and bolster our immune systems—and much more. These SCFAs, in fact, are even involved in neurotransmitter production (you can read more about this in a below section)! However, not all bacteria are capable of digesting those carbs for us. Some bacteria would much rather digest—or metabolize—proteins and amino acids. Just like the digestion of carbs produces SCFAs, the digestion of proteins by our bugs produces  many  byproducts that are toxic to our bodies and lead to dysbiosis and inflammation. Scientists have found that people with Major Depressive Disorder have elevated levels of gut bacteria that snack on proteins (and therefore elevated levels of toxic biproducts circulating through their digestive tracts), and reduced levels of the bacteria that snacks on carbs (and reduced levels of those helpful SCFAs!)

Micronutrient Production: Our microbiome is responsible for  synthesizing vitamins important to our physical and mental health. For instance, strains of healthy bacteria can synthesize and generate folate and thiamine—two micronutrients known to be implicated in depressive symptoms. Low blood levels of folate and thiamine have been associated with depression. Dysbiosis that results in low production of these key micronutrients could very well be contributing to mental illness.

Inflammation: We’ve talked much about inflammation on this blog before, but it warrants repeating: dysbiosis can lead to irritable bowel syndrome and a leaky gut, which in turn can lead to significant chronic inflammation throughout our body and brain. But there’s another important element at play when it comes to our gut and inflammation: when our cytokines—the proteins responsible for our inflammatory response—are “upregulated”, our body’s synthesis of serotonin can be impacted—and recall, low serotonin levels can be a key indicator of depression!

Neurotransmitter production: Certain gut bacteria are capable of making the very neurotransmitters implicated in a range of mental illnesses, including serotonin, norepinephrine, and dopamine. One type of bacteria, Bifidobacterium, is particularly efficient at this and is found in lower amounts in people who are depressed. The production of neurotransmitters in our gut is perhaps the most direct way our microbiome impacts our mood—and studies show that supplementation our gut microbiome with probiotics that help produce those neurotransmitters can actually have an antidepressant-like effect. Incredible!

Diet: Our diet can certainly have an impact on our mood through the interaction between the food we eat and our gut microbiome. A diet rich in Omega-3 fatty acids, like a Mediterranean diet, has been shown to reduce inflammation and have an impact on depression.

Treating Brenda’s Gut—and Her Depression

Brenda’s stool test revealed both low diversity and low abundance of bacteria, and the presence of inflammation. With the understanding that Brenda was  suffering from gut dysbiosis, I placed her on a probiotic, and a prebiotic, and a Mediterranean diet to address her gastrointestinal symptoms and inflammation, and Vitamin D3 to address its deficiency in her body—this vitamin also has anti-inflammatory properties.  The next time I saw her, as she gave me her update, I felt what I imagine it must be like to be a surgeon who rapidly cures people.

“Dr. Bruce, I feel fantastic! Overnight I began to feel physically better with lessening stomach pains, and an absence of heartburn and burping. My urgent need to have a bowel movement went away three days later. The panic attacks are now gone, the mood swings are mostly gone, my executive functioning is somewhat better, and while I remain depressed  the symptoms have lessened a lot.”

As we have reported in prior Mighty Moody Microbiome blogs, you can begin to restore health to your microbiome in as little as 24 hours (or begin to damage it that quickly, too!) —and for Brenda this restoration was exactly what happened through her taking probiotics and prebiotics and initiating a Mediterranean diet. Next week, we’ll dig in more specifically to the role probiotics can play in treating depression. Stay tuned!

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*Although lessons learned from the treatment of actual patients are included in the patient stories on this website and blogsite, the historical events and facts represented have been changed to protect the identities of any real patients and to protect their confidentiality. For example, the names, ages, careers, the number and sex of their children, as well as the careers of the patients’ parents have been deliberately altered, as well as other alterations that have been made. Consequently, all characters appearing on these sites are fictitious. Any resemblance to real persons, living or dead, is purely coincidental.

**Author’s financial disclosure: Genomind and Potomac Psychiatry have an ongoing marketing collaboration aimed at raising visibility for Genomind pharmacogenomics services and Potomac Psychiatry’s Genetic Testing Consultations. Dr. Kehr holds no ownership interest in Genomind and receives no consulting fees.

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