Leaky Gut and The Depression-Gut Connection
Do you know that mental health issues like depression and anxiety can be linked to the health of your gut?
When the gut lining isn’t strong enough to do its job, we’re dealing with leaky gut. In other words, increased intestinal permeability. This is often due to imbalances in good and bad bacteria and can lead to mental health concerns!
Leaky gut is strongly linked in the scientific literature with depression and anxiety. Let’s dive into the science of why and discover some tips and tricks to help yourself heal.
The Vagueness of IBS
Studies show that about 80% of people diagnoses with IBS actually have underlying infections. Small Intestinal Bacterial Overgrowth (SIBO) and Small Intestine Fungal Overgrowth (SIFO) are common imbalances in the gut microbiome. People with digestive concerns often also dealing with parasites or have too few healthy gut bacteria that fermented foods and probiotics provide.
These infections and imbalances can make a mess of our mood, energy levels, and ability to recover from life’s daily challenges. If left alone and unresolved, the vicious cycles of inflammation that come with these imbalances can self-perpetuate. Consequently, these infections and imbalances can even lead to brain cell damage.
Understanding the biological systems involved is the first step in attaining proper treatment for symptoms that may not initially seem gut-related. In other words, symptoms like depression, anxiety, insomnia, moodiness, fatigue and lack of motivation are not just be in your head.
Tryptophan and Serotonin: When Things Work the Way They Should
Serotonin is an extremely important neurotransmitter, or brain chemical, involved in emotion and mood. Treatments for depression often involve anti-depressant drugs called selective serotonin reuptake inhibitors (SSRIs). These drugs recirculate your body’s serotonin, whether those levels are optimal or low from the onset. Unfortunately, if infections are leading to low serotonin in your body, these drugs never solve the underlying problem. In short, they just cover up your symptoms.
The body and brain naturally create serotonin from tryptophan. Tryptophan is a protein in foods like nuts, meat (not just turkey,) lentils, cheese, beans, and eggs. The serotonin pathway coverts tryptophan into 5HTP, and 5HTP into serotonin. Eventually, serotonin converts into melatonin, which regulates our circadian rhythm and sleep cycle.
The Serotonin Hypothesis
In the 1960s, it was largely hypothesized that imbalances in brain chemistry, namely a deficiency in 5HT, 5HTP and serotonin, were the cause of depression.
However, we understand today that depression and anxiety are complex and variable mood states. A variety of factors play a role in the development and persistence of depressive symptoms.
These factors include but are not limited to:
- Digestive and gut microbiome health
- Nutrition and vitamin deficiency
- Socioeconomic status
- Experiences of trauma and oppression
- Lack of sunshine and Vitamin D
- Environmental exposure
- The interplay of our neurobiology and the world around us
The serotonin hypothesis is complex and controversial. It is a simplified version of reality. There are many pathways to depression and anxiety, but today let’s focus on the role that gut health plays in mental health.
Where Things Go Wrong: Tryptophan and Kynurenin
When inflammation in the gut sets off red flags (chemical messengers called cytokines,) the body uses enzymes to shift tryptophan from the serotonin pathway to the kynurenin pathway.
While the kynurenin pathway usually ticks along in the background protecting us from low-grade inflammation, infections can make it explode into activity. This alternate pathway attempts to perform damage control, but it can run amok and actually hurt while it tries to help.
In addition, tryptophan that would otherwise become serotonin is taken out of the normal pathway. In other words, less serotonin is circulating in your body. This can have downstream effects on gut health. It is likely these gut-brain imbalances play a role in keeping us depressed and anxious.
Kynurenin and Quinolate
The first product in the kynurenin pathway, KYN-A, reduces inflammation in the brain. This is through a mechanism similar to some anesthetics and drugs like ketamine and PCP. However, if this pathway is excessively stimulated (such as with a gut infection), kynurenin can also produce quinolate.
Quinolate works opposite to KYN-A, soothing the initial inflammation and reversing the negative effects of KYN-A. Unfortunately, quinolate can also be toxic and damaging. High levels can injure or kill brain cells.
The Brain Butts In
The brain begins cutting off protein pumps when this pathway is hyper-stimulated that would otherwise allow serotonin to enter and circulate within brain cells. This takes away access to already-dwindling supplies of serotonin.
These effects compound for people with low vitamin B6. People experiencing depression, anxiety, or a gut infection that has reduced your ability to absorb nutrients from your food often have low B vitamins from the git-go.
We use B6 for the production of both serotonin and KYN-A, so an overactive kynurenin pathway depletes another scarce and protective resource.
What This Means for YOU:
- Once triggered by inflammation, the now-overactive kynurenin pathway “steals” tryptophan from the serotonin path, blocking access to the serotonin we have left.
- Our ability to regulate our emotions and mood takes a one-two knockout punch without serotonin.
- Gut health is compromised without enough serotonin
- It eventually becomes difficult to regulate sleep as serotonin is necessary for the creation of melatonin as well.
- This cycle results in fatigue, depressed and/or anxious mood, and even further inflammation, which feeds the whole double-bad cycle.
Overgrown Gut Bacteria Release Toxins
Toxins from bad, or pathogenic, bacteria are called lipopolysaccharides (LPS). When these LPS escape our leaky gut, they set off the cytokine (chemical messenger) warning system. This can trigger the kynurenin pathway above.
Too many cytokines in the brain can also lead to Cytokine Sickness. These cytokines are supposed to act protectively. However, too many can harm brain cells and imbalance our neurotransmitters. LPS can also turn our immune cells on overdrive. Immune cells which normally act as clean-up crews can get overexcited, attacking healthy brain cells.
This reaction has a measurable effect on the brain and body. Studies on human subjects have shown that within hours of administering LPS to human study participants, depression and fatigue increase, and social interest goes down significantly.
That is: when there are bad bacteria in your digestive system, they can trigger chemical reactions that make you feel sad, socially withdrawn and anxious.
Back to the Brain
In the brain, the insula becomes more active when there is inflammation. The insula is a part of the brain that monitors and moderates activity in organs such as our gastrointestinal track, which runs from mouth to anus. Overactivity in this area of the brain sparks our sympathetic nervous system into a ‘fight or flight’ response. This is the opposite of ‘rest and digest,’ or parasympathetic activity which we need for healthy digestion and to feel calm and safe.
With the body on high alert, there is no opportunity for the gut to heal or recover. This constant high alert system also prevents normal, healthy intestinal movements, which might otherwise help to flush out LPS.
That is to say, inflammation in the gut can be a cause of constipation. Laxatives can be helpful short term, thought long term, they simply cover up the root cause of the problem.
The problem can sometimes be insula-driven slowed GI emptying due to inflammation.
Elsewhere in the brain, the anterior cingulate shows less activity. Low activity in this area impacts attention and mood. Overstimulation of the immune system is common. In depression, this manifests as ‘depression sick syndrome,’ where the body reacts as if it were infected with a bug or virus.
For people with depression or a gut infection, it may seem as if they are constantly fighting off a cold or the flu.
Sleeping too much, lacking motivation, not wanting to leave the couch or bed are all symptoms of depression. This makes sense when we think about the neurobiology here. It’s not all in your head – it’s in the complex bidirectional relationship between the digestive system and the brain.
- Gastrointestinal infections and imbalances have a hugely negative impact on the lives of millions of people worldwide
- These imbalances and the inflammation that comes from imbalances in the gut microbiome can change the normal chemical pathways in our brains
- Our brain chemistry changes in response to inflammation and LPS activity, and serotonin and melatonin don’t get made in the volume we need
- We need these chemicals to regulate our mood, sleep and gut motility/health
- When our brain chemistry is out of balance, we can feel depressed and anxious, have a harder time sleeping, feel less motivated
- This cycle can increase cortisol, a stress hormone, turning our bodies on high alert
- Normal rest and healing are prevented, which can lead to what is commonly referred to as “adrenal fatigue” or HPA-dysregulation, which will be detailed in a future article.
Toxins and Inflammation Can Turn Our Immune Systems Against Us
This can make us feel sick and even potentially damaging our brains in a number of ways. Each of these symptoms is a problem in their own right. It can sometimes be difficult to see past the end result – depression, trouble sleeping, always feeling sick, etc – and find the underlying cause. However, when you heal your gut, health and mood can improve across the board.
What To Do To Heal
The first step is to figure out WHY you have a leaky gut. Start an elimination diet and find a Functional Medicine provider to run the right tests. I recommend an advanced stool test (not the one the GI doc or your PCP runs) and a breath test for SIBO.
From there, you need to deal with your results – kill of any overgrown bacteria or parasites, rebalance your small intestine.
Meanwhile, start an elimination diet when you go off the most inflammatory foods for at least 30 days. This is key. If you’re eating something that is causing inflammation, this cycle will only get worse.
Once any infection is identified and addressed, there’s a lot you can do to improve mood by reducing LPS and ending the vicious cycle.
To healing both mind and body, I recommend eating real whole foods, getting enough sleep (like it’s your #1 job,) exercise (even just walking is great) and meditation daily. These things are vital for good mind-body health. Don’t scrimp – you’re worth it.
Some of my favorite supplements to help with mental health and leaky gut are as follows – be sure to talk with your own clinicians and PCP before starting any supplements or treatments.
- 5HTP*, the chemical step between tryptophan and serotonin, can be given as a supplement, to repair leaky gut and replenish serotonin. 50 mg with lunch and dinner for up to 3 months.
- Probiotics – there are several on the market that specifically target the gut-brain
- Prebiotics – my go-to is Arabinogalactan, a resistant starch
- Glutamine – 1000 mg twice/day, optimally between meals (but if you can’t remember that, take it right before you eat)
- Aloe vera (internal part of the leaf)
- Antibody support supplements (like lactoferrin, SBI)
- Probutyrate to support healthy immune response
Note: please do not take 5HTP if you are on anti-depressants!
The biological systems that govern our mood and immune system are complex. By treating the cause instead of the symptoms, we can stop the negative chain-reactions at the beginning, and restore wellness and balance in our bodies and minds.
The best way to treat depression, anxiety, fatigue and other mood concerns? Start with the gut!
Victoria Albina, NP, MPH is a licensed and board certified Family Nurse Practitioner, herbalist and life coach, with 20 years experience in health and wellness. She trained at the University of California, San Francisco, and holds a Masters in Public Health from Boston University and a bachelors from Oberlin College. She comes to this work having been a patient herself, and having healed from a lifetime of IBS, GERD, SIBO, fatigue, depression and anxiety.
She is passionate about her work, and loves supporting patients in a truly holistic way - body, mind, heart and spirit. A native of Mar del Plata, Argentina, she grew up in the great state of Rhode Island, and lives in NYC with her partner. A brown dog named Frankie Bacon has her heart, and she lives for steak and a good dark chocolate.