gut-brain connection, hope, depression recovery, heal, healing, gratitude, grateful

The Gut-Brain Connection: Root Cause Solutions for Depression

My clients suffering from depression are often not aware of the profound Gut-Brain Connection and how it plays into their darkest moods. They are quite curious when rather than focusing solely on descriptions of their thoughts and feelings (as vitally important as they are), I expand our discussion to their gut health and what they eat on a regular basis. I recommend food plans and gut-healing regimens as part of their mood improvement strategy.

What’s the gut got to do with it? Join me for Kathleen’s journey from treatment-resistant depression that left her feeling exhausted and hopeless, to full recovery of her vibrant mood and energy through a comprehensive gut-restoration plan.

Kathleen had Life-Long, Treatment Resistant Depression

“Doc, I’ve been depressed for years. I can’t seem to get off these antidepressants. They seem to work for awhile, then stop working. My therapist says I have a chemical depression, I come from a depressed family, it’s in my genes. I know I’m a difficult case. I fear there is nothing more that can be done for me.”

This was what Kathleen, a forty-two year old new client of mine, had to say at our first meeting. She’d been depressed since she was a college student in her early twenties. She had been on and off antidepressant medications since that time. She self-medicated with alcohol, cigarettes, sex with the wrong people, and perfectionism. Nothing seemed to work–or made things worse. She felt ashamed, exhausted, and hopeless. Her therapist had heard I worked successfully with people who had difficult problems–what was there to lose by this last ditch effort to help her client?

After a thorough evaluation of her health history and core elements of her life story, there were important clues that her depression was engendered by the Gut-Brain Connection:

  • She had received antibiotics extensively as a young child for recurrent acute otitis media (ear infections) and again for two years straight to treat acne as a teenager.
  • She reported routine gut-related symptoms: constipation, diarrhea, gas, bloating, and abdominal pain after eating.
  • She had additional symptoms and physical signs of inflammation: joint pain, eczema, sinus congestion, migraine headaches, and painful, heavy periods.
  • She consumed a standard American diet: high in refined carbohydrates, processed grains, dairy products; and low in nutrient density.

Does this sound at all like you?

Depression is a Symptom of Gut-Brain Connection Imbalances

Depression, like most persistent problems, is a symptom without a single cause. In fact, as much as we love certainty and simplicity in medicine, there are as many causes for depression as there are people who suffer from it. It’s much more likely to be multifactorial, encompassing a host of  issues–genetics, lifestyle, history of trauma, coping skills, level of social support, and myriad health issues. A vastly unappreciated and under-explored contributor to depression is the Gut-Brain Connection.

Protocoled strategies for treating depression over-simplify what it takes to heal–and often don’t work. I’ve met many of these folks, like Kathleen, in my consultation room. They’ve put their faith in the simplistic drug treatments offered by their well-intending doctors, faithfully taking the prescribed antidepressants–hopeful–following instructions to the letter but do not get better. The promise of a solution that worked for one—or a few—to a heterogeneous group will inevitably fail for some, leading to disengagement and loss of hope.

It’s important to know that depression is not a disease–it’s a symptom. This is how we must now view depression in light of what we know about the gut-brain connection in depression, and the preponderance of evidence that shows how the depressed brain is inflamed and the inflamed brain is depressed.

By understanding depression as a symptom we’re free to look at the individual and the unique attributes they bring to their experience of depression. This opens endless and more powerful ways to treat them–like strategies to heal gut-brain connection imbalances.

The Gut-Brain Connection in Depression

Our bodies consist of elegant, interconnecting systems of tissues, cells, and information molecules, that allow for close communication between geographically distant parts. This is why the gut and brain are as close and interdependent as members of our families. Science proves this tight gut-brain connection, showing us unequivocally that the brain and gut speak intimately with one another in ways that profoundly influence the function and health of the other.

The cells of our gut lining–which includes the bacterial cells that reside within the gut (the microbiome)–manufacture the same neurochemicals as brain cells that modulate it’s function–influencing mood, cognition, and alertness. These gut-derived “brain” chemicals, like serotonin and GABA, will circulate into the brain and contribute to its function.

In addition, the immune cells of the gut cross-talk with immune cells of the brain, delivering alarm molecules when there’s trouble. When immune cells within the gut are activated–by food proteins, allergens, toxins, infections, or gut permeability breakdown–inflammation ensues–a chemical storm designed to protect us, making its way to the brain and priming it for action against the potential offender. The brain activated in this way by inflammation is much more susceptible to changes in mood, cognition, and alertness, and is closely linked to depression.

How the Gut-Brain Connection Leads to Depression in the Inflamed Brain

A key player in the gut-brain connection in depression is inflammation. This can be engendered by a host of common gut problems I see in my clients:

  • immune-mediated sensitivities to foods we ingest
  • pathogenic organisms or imbalances in our gut flora
  • Excess sugar and refined carbohydrate ingestion
  • Toxins
  • Impairment in gut lining permeability, leading to increased immune responsiveness and systemic toxin exposure

We typically think of inflammation as something we can see: the red swollen joint of an autoimmune disorder, like rheumatoid arthritis; or infected external wound. Or something we overwhelmingly feel and recognize, like the body aches and fever that accompany the flu.

But there is also inflammation that is ubiquitous and more hidden to the untrained eye–like the inflammation that accompanies obesity, blood sugar dysregulation (like in diabetes), high levels of stress, and the gut-related problems I listed above. These are types of inflammation that can go unnoticed and work insidiously behind the scenes to create big problems–like in Kathleen.

Kathleen’s Depression Busting Strategy: Healing the Gut-Brain Connection

My evaluation of Kathleen determined that, in addition to suffering from depression, she had gut flora imbalances caused by extensive exposure to antibiotics, food sensitivities resulting from gut lining permeability breakdown, nutrient deficiencies (folate, vitamin B12, magnesium, zinc, and antioxidants), small intestinal bacterial overgrowth (SIBO), and mitochondrial energy impairment (likely a culmination of everything else).

Any of these problems alone would have significant effects on her brain and could lead to depression. The combination of factors was overwhelming and were not addressed by her antidepressant medications–leading to treatment failure.

Our initial treatment plan focused on gut repair and support, correction of nutrient deficiencies, energy support, and reduction of excess stress:

  • GRIN Food Plan (“Gut-Immune Restoration Intensive Nutrition”) with low FODMAPs (to reduce bacterial overgrowth in her small bowel): to remove foods most likely activating gut immune cells, reduce inflammation, heal gut mucosa barrier, reduce bacterial overgrowth in the small bowel, and supply intensive nutrition with regards to macronutrients (healthy protein, fat, and complex carbohydrates) and micronutrients.
  • Digestive enzymes and Betaine HCL to support digestion.
  • Nutritional supplements to specifically target micronutrient deficiencies and address inflammation (curcumin, omega-3 fats, GLA).
  • Probiotics (lactobacilli, bifidobacteria, and saccharomyces boulardii; 60 billion organisms twice daily). No prebiotics at this time due to SIBO.
  • Avoidance of all non-steroidal anti-inflammatory drugs (Ibuprofen, Aleve, etc), alcohol, and pesticide-containing foods.
  • Targeted gut mucosal lining repair nutrients: l-glutamine, omega-3 fats, micronutrient, antioxidants.
  • Five minute guided meditation each morning using phone app, deep breathing, moderate exercise, good sleep, and scheduled breaks for fun and connection.

Kathleen was highly motivated, and with the help of my functional nutritionist colleague, was able to implement the food plan right away. Within just a few days her gut symptoms completely resolved. Within a week her mood and energy both improved. By the time I saw her in follow up one month later she was elated to report that her depression had completely lifted and she had never felt so good. In addition, her eczema cleared up, sinus congestion resolved, joint pain and migraines were gone, and her last period was less painful. She expressed enthusiasm for weaning off of her antidepressant medication, which she successfully did over the ensuing couple of months.

This is not an unusual story and Kathleen’s outcome is what I expect to have happen when we treat depression as a symptom and address the root cause factors–making gut repair and reduction of inflammation a core part of our strategy.

The specifics of the depression busting strategy will be different for everyone, but the common denominator is how we work with what we determine to be the root causes. Knowing the powerful link between depression and the inflamed brain allows us to work with the common upstream source of that inflammation–the gut.


Karyn Shanks, MD. The Gut-Brain Connection–Part Two–Action Steps for Healing Depression. 2017.

MS Cepeda et al. Depression is Associated with High Levels of C-Reactive Protein and Low Levels of Fractional Exhaled Nitric Oxide: Results from the 2007-2012 National Health and Nutrition Examination Surveys. J Clin Psychiatry 77 (12), 1666-1671. 12 2016.

CD Rethorst et al. Inflammation, Obesity and Metabolic Syndrome in Depression: Analysis of the 2009-2010 National Health and Nutrition Survey (NHANES). J Clin Psychiatry 75 (12), e1428-e1432. 12 2014.

Charles L. Raison et al. Is Depression an Inflammatory Disorder? Curr Psychiatry Rep. 2011 Dec; 13 (6): 467-475.

Alper Evrensel, et al. The Gut-Brain Axis: The Missing Link in Depression. Clin Psychopharmacol Neurosci. 2015 Dec; 13 (3): 239-244.

Karyn Shanks, MD. The Liftoff Gut-Immune Restoration Intensive Nutrition (GRIN) Food Plan. 2016.

Karyn Shanks, MD. Healing Foods: My Favorite Healthy Fats. 2017.

Institute for Functional Medicine. FODMAP Intolerances. 

FODMAP Foods, FODMAP Elimination, SIBO, Small Bowel Bacterial Overgrowth, Small Intestinal Bacterial Overgrowth, IBS, Irritable, Bowel Syndrome, Gut Health, Functional Mediine
Karyn Shanks MD


Karyn Shanks, MD, is a physician who lives and practices in Iowa City. Her work is inspired by the revolutionary science of Functional Medicine, body-mind wisdom, and the transformational journeys of thousands of clients over her twenty-eight year career. She believes that the bones of healing are in what we do for ourselves.


    This is me. This is very much me. I was on a daily antibiotic for years as a child due to heart issues. The digestive upset. The pain. The overwhelming depression.
    I know this is me, because when I was pregnant with my first I had gestational diabetes. I cut out alllll of the junk. To a fault, as I wasn’t getting enough fat intake & lost too much weight, but for the 3+ years I stayed away from processed foods, I felt the absolute best I have ever felt. Then life got in the way, another pregnancy that was not GD positive, moving, growing, running around…. I am so unhappy now, but I don’t know where to start. Where to go for help. But I believe every word of this.


    Kris, I’m so glad you found this and recognize what is part of your struggle with depression. I see this in my practice all of the time! You’ve inspired me to write a follow up article with some very specific action steps for recovering from depression through a food-gut restoration program… stay tuned!


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