Can A “Leaky Gut” Cause Depression?

Written By: Kelley Herring

You’ve almost certainly heard of “leaky gut” and the health issues it can cause. But just in case, let’s quickly cover the bases…

When your body is healthy, your digestive tract serves as a barrier between your gut and your bloodstream. But the epithelial lining of your gut is very sensitive. And it can easily become compromised. When this barrier becomes too porous, undigested food, yeast, pathogens and other foreign matter is allowed to enter your bloodstream.

This, in turn, can cause chronic inflammation, allergic reactions, food intolerances, autoimmune illness – and a HOST of symptoms, seemingly unrelated to the gut.

Today, you’ll discover how the health of your gut plays a role in your mood, and the simple nutritional strategies you can use to improve your gut’s integrity.

But first…

Is Leaky Gut a Myth?

You might be surprised, but many doctors and mainstream medical institutions outright dismiss the idea of “leaky gut.” Some claim the condition doesn’t even exist!

Perhaps they should broaden their horizon just a bit, because the National Library of Medicine database, PubMed, reveals more than 14,000 results for the term “intestinal permeability”!

Peer-reviewed scientific studies linking this condition to everything from autoimmunity (and brain autoimmunity), to Alzheimer’s, heart disease, IBS, obesity, and more.ⁱ

And it should come as no surprise, considering Hippocrates’ observation that “all disease begins in the gut”.

But how does what happens in your gut… play a role in the function of your brain?

The Brain-Gut Connection

Your digestive tract contains the second highest number of nerves in your body! And your gut is in constant communication with your brain. If you have “leaky gut”, these messages can cause unusual neurological symptoms.

In the words of neuroscientist, John F. Cryan, PhD:

“There is no question that the gut microbiome regulates fundamental brain processes important for the development of neurological diseases.”

Let’s take a look at the common neurological symptoms linked with leaky gut:

1. Anxiety & Depression – Studies show increased inflammation is associated with anxiety, depression, hyperactivity and other mood disorders.^{ii ,iii ,iv ,v}
   
   
2. Brain Fog – A common complaint among those with autoimmune disease and chronic pain. Digestive inflammation impairs gut-brain communication, which can lead to a numb feeling of “unreality”, poor focus, impaired learning and memory.^vi
   
   
3. Muscle Twitches – Leaky gut can cause deficiencies of magnesium and potassium, which can lead to muscle twitches, cramps and spasms.^vii
   
   
4. Schizophrenia – A study published in Schizophrenia Research, showed that inflammation in the circulatory and nervous systems can be linked to mental illness.^viii

In addition to these neurological conditions, intestinal permeability has also been linked to Alzheimer’s, fibromyalgia, chronic migraines, autism and neuropathy.^{ix ,x ,xi}

Leaky Gut: How Bad Bacteria Can Cause a Really Bad Mood

The inflammatory response is a key biological process. It’s also involved in creating the symptoms of depression. And while cytokines are best-known for inducing these symptoms, so too are other inflammatory compounds, known as lipopolysaccharide (LPS).

Lipopolysaccharides (LPS) are a component of the outer membrane of certain bacteria. Since the body is evolutionarily trained to seek-and-destroy these bad bacteria, they are seen as a threat – to which the body mounts a strong immune response.^xii

Researchers from Belgium conducted a study to determine if increased gut permeability and resulting increase in LPS was linked with depression, by measuring antibodies in healthy controls compared to patients with major depression.

The researchers found significantly higher levels of LPS antibodies in patients with major depression. In fact, the differences were so significant that levels of these compounds could be used to diagnose major depression with an accuracy of just over 90%!^xiii

Other symptoms associated with increased antibodies against LPS include: Fatigue, gastrointestinal symptoms and a subjective feeling of infection.

 

Heal Your Gut… Help Your Mood!

Healing leaky gut can go a long way to improving your mood.

Enjoying foods rich in l-glutamine, like bone broth, and taking l-glutamine supplements is the first course of action.^xiv

It might also be a good idea to use anti-inflammatory, gut-healing herbs such as turmeric and to ensure that ample amounts of the dietary nutrients required for intestinal epithelial tissue repair are consumed. These include easily assimilated forms of protein, vitamins A and E and zinc.^xv,xvi

Here are some excellent food sources of gut-healing nutrients:

• Grass-fed beef, lamb, bison, elk

• Organ meats – especially liver and bone marrow

• Clean-sourced & wild-caught oysters, mussels, clams, shrimp, crab

• Clean-sourced & wild-caught salmon, halibut, sardines, mackerel

And it’s not just what you eat… but also what you don’t!

Foods and compounds known to increase intestinal permeability include:

1. Inflammatory Neolithic Foods: Gluten, grains, legumes, pasteurized dairy, alcohol, and sugar can all contribute to leaky gut.^{xvii,xviii ,xix ,xx}
   
   
2. Environmental Toxins: Exposure to toxic heavy metals such as lead, mercury or cadmium can cause irritation in the intestinal lining and promote leaky gut.^xxi,xxii
   
   
3. BPA: This common chemical found in can liners has been shown to damage intestines, allowing toxins and pathogens to more easily enter the body.^xxiii
   
   
4. Medications: NSAID pain relievers, antibiotics, steroids, birth control pills and acid-reducing drugs can greatly increase risk of leaky gut.^xxiv,xxv

Finally, stress is another contributing factor. A study published in the Journal of Physiology and Pharmacology showed that usually harmless microbes actually turned pathogenic in response to stress hormones.^xxvi

And we can’t forget about sleep! Numerous studies have linked insomnia with depression via the microbiome-gut-brain axis, so be sure you’re sleeping sufficiently and soundly to promote a positive mental outlook.^xxvii,xxviii

References

i Pub Med Search for “Intestinal Permeability” https://www.ncbi.nlm.nih.gov/pubmed/?term=intestinal+permeability

ii Foster, J., McVey Neufeld, K. Gut-brain axis: how the microbiome influences anxiety and depression. Trends in Neurosciences. May 2013. Vol 36, No. 5

iii Kiecolt-Glaser JK1, Derry HM1, Fagundes CP1.Inflammation: depression fans the flames and feasts on the heat.Am J Psychiatry. 2015 Nov 1;172(11):1075-91. doi: 10.1176/appi.ajp.2015.15020152. Epub 2015 Sep 11.

iv Kelly JR1, Kennedy PJ2, Cryan JF3, Dinan TG1, Clarke G1, Hyland NP4.Breaking down the barriers: the gut microbiome, intestinal permeability and stress-related psychiatric disorders.Front Cell Neurosci. 2015 Oct 14;9:392. doi: 10.3389/fncel.2015.00392. eCollection 2015.

v Stevens BR1,2, Goel R1, Seungbum K1, Richards EM1, Holbert RC2, Pepine CJ3, Raizada MK1.Increased human intestinal barrier permeability plasma biomarkers zonulin and FABP2 correlated with plasma LPS and altered gut microbiome in anxiety or depression.Gut. 2018 Aug;67(8):1555-1557. doi: 10.1136/gutjnl-2017-314759. Epub 2017 Aug 16.

vi Galland L1.The gut microbiome and the brain.J Med Food. 2014 Dec;17(12):1261-72. doi: 10.1089/jmf.2014.7000.

vii Anderson B, Pitsinger A. Improvement in chronic muscle fasciculations with dietary change: a suspected case of gluten neuropathy. J Chiropr Med. 2014;13(3):188–191. doi:10.1016/j.jcm.2014.01.002

viii Severance, E. Autoimmune diseases, gastrointestinal disorders and the microbiome in schizophrenia: more than a gut feeling. Schizophrenia Research. Sept 2016. Volume 176, Issue 1, P 23-25

ix Bekkering P1, Jafri I, van Overveld FJ, Rijkers GT.The intricate association between gut microbiota and development of type 1, type 2 and type 3 diabetes.Expert Rev Clin Immunol. 2013 Nov;9(11):1031-41. doi: 10.1586/1744666X.2013.848793. Epub 2013 Oct 21.

x Esnafoglu E1, Cırrık S2, Ayyıldız SN3, Erdil A4, Ertürk EY4, Daglı A4, Noyan T3.Increased Serum Zonulin Levels as an Intestinal Permeability Marker in Autistic Subjects.J Pediatr. 2017 May 11. pii: S0022-3476(17)30487-0. doi: 10.1016/j.jpeds.2017.04.004. [Epub ahead of print]

xi Goebel A1, Buhner S, Schedel R, Lochs H, Sprotte G.Altered intestinal permeability in patients with primary fibromyalgia and in patients with complex regional pain syndrome.Rheumatology (Oxford). 2008 Aug;47(8):1223-7. doi: 10.1093/rheumatology/ken140. Epub 2008 Jun 7.

xii Maes M, Kubera M, Leunis JC. M-Care4U Outpatient Clinics, and the Clinical Research Center for Mental Health, Belgium. The gut-brain barrier in major depression: Intestinal mucosal dysfunction with an increased translocation of LPS from gram negative enterobacteria (leaky gut) plays a role in the inflammatory pathophysiology of depression.Neuro Endocrinol Lett. 2008 Feb 18;29(1)

xiii Maes M, Kubera M, Leunis JC. M-Care4U Outpatient Clinics, and the Clinical Research Center for Mental Health, Belgium. The gut-brain barrier in major depression: Intestinal mucosal dysfunction with an increased translocation of LPS from gram negative enterobacteria (leaky gut) plays a role in the inflammatory pathophysiology of depression.Neuro Endocrinol Lett. 2008 Feb 18;29(1)

xiv Achamrah N1, Déchelotte P, Coëffier M.Glutamine and the regulation of intestinal permeability: from bench to bedside.Curr Opin Clin Nutr Metab Care. 2017 Jan;20(1):86-91.

xv McCullough FS1, Northrop-Clewes CA, Thurnham DI.The effect of vitamin A on epithelial integrity.Proc Nutr Soc. 1999 May;58(2):289-93.

xvi Shao Y1, Wolf PG2, Guo S1, Guo Y1, Gaskins HR3, Zhang B4.Zinc enhances intestinal epithelial barrier function through the PI3K/AKT/mTOR signaling pathway in Caco-2 cells.J Nutr Biochem. 2017 May;43:18-26. doi: 10.1016/j.jnutbio.2017.01.013. Epub 2017 Jan 31.

xvii Leech B1,2, Schloss J1, Steel A1,2.Treatment Interventions for the Management of Intestinal Permeability: A Cross-Sectional Survey of Complementary and Integrative Medicine Practitioners.J Altern Complement Med. 2019 Jun;25(6):623-636. doi: 10.1089/acm.2018.0374. Epub 2019 Apr 29.

xviii Shimada S1, Tanigawa T1,2, Watanabe T1,2, Nakata A1, Sugimura N1, Itani S1, Higashimori A1,2, Nadatani Y1, Otani K1, Taira K1, Hosomi S1, Nagami Y1, Tanaka F1, Kamata N1, Yamagami H1, Shiba M1, Fujiwara Y1,2.Involvement of gliadin, a component of wheat gluten, in increased intestinal permeability leading to non-steroidal anti-inflammatory drug-induced small-intestinal damage.PLoS One. 2019 Feb 20;14(2):e0211436. doi: 10.1371/journal.pone.0211436. eCollection 2019.

xix de Punder K1, Pruimboom L.The dietary intake of wheat and other cereal grains and their role in inflammation.Nutrients. 2013 Mar 12;5(3):771-87. doi: 10.3390/nu5030771.

xx Lambertz J1, Weiskirchen S1, Landert S2, Weiskirchen R1.Fructose: A Dietary Sugar in Crosstalk with Microbiota Contributing to the Development and Progression of Non-Alcoholic Liver Disease.Front Immunol. 2017 Sep 19;8:1159. doi: 10.3389/fimmu.2017.01159. eCollection 2017.

xxi Vázquez M1, Vélez D, Devesa V.In vitro evaluation of inorganic mercury and methylmercury effects on the intestinal epithelium permeability.Food Chem Toxicol. 2014 Dec;74:349-59.

xxii Tinkov AA1, Gritsenko VA2, Skalnaya MG3, Cherkasov SV2, Aaseth J4, Skalny AV5.Gut as a target for cadmium toxicity.Environ Pollut. 2018 Apr;235:429-434. doi: 10.1016/j.envpol.2017.12.114. Epub 2018 Jan 5.

xxiii Braniste, V., Jouault, A., Gaultier, E., et al. Impact of oral bisphenol A at reference doses on intestinal barrier function and sex differences after perinatal exposure in rats. Proc Natl Acad Sci U S A. 2010 Jan 5; 107(1): 448–453.

xxiv Yoshikawa K1,2, Kurihara C3, Furuhashi H3, Takajo T3, Maruta K3, Yasutake Y3, Sato H3, Narimatsu K3, Okada Y3, Higashiyama M3, Watanabe C3, Komoto S4, Tomita K3, Nagao S4, Miura S5, Tajiri H6, Hokari R3.Psychological stress exacerbates NSAID-induced small bowel injury by inducing changes in intestinal microbiota and permeability via glucocorticoid receptor signaling.J Gastroenterol. 2017 Jan;52(1):61-71. doi: 10.1007/s00535-016-1205-1. Epub 2016 Apr 13.

xxv Bjarnason I1, Takeuchi K.Intestinal permeability in the pathogenesis of NSAID-induced enteropathy.J Gastroenterol. 2009;44 Suppl 19:23-9. doi: 10.1007/s00535-008-2266-6. Epub 2009 Jan 16.

xxvi Konturek PC1, Brzozowski T, Konturek SJ.Stress and the gut: pathophysiology, clinical consequences, diagnostic approach and treatment options. J Physiol Pharmacol. 2011 Dec;62(6):591-9.

xxvii Barceló A1, Esquinas C2, Robles J3, Piérola J4, De la Peña M5, Aguilar I3, Morell-Garcia D6, Alonso A5, Toledo N7, Sánchez-de la Torre M8, Barbé F8.Gut epithelial barrier markers in patients with obstructive sleep apnea.Sleep Med. 2016 Oct;26:12-15. doi: 10.1016/j.sleep.2016.01.019. Epub 2016 Sep 28.

xxviii Yuanyuan Li,1 Yanli Hao,2 Fang Fan,1,* and Bin Zhang3,*The Role of Microbiome in Insomnia, Circadian Disturbance and Depression. Front Psychiatry. 2018; 9: 669. Published online 2018 Dec 5. doi: 10.3389/fpsyt.2018.00669