How Does Leaky Gut Relate to Cognitive Decline?

by Brooklin White MS, RDN, LDNLifestyle
Hands shaped as a heart

The human intestine contains the small intestine (~22 ft long) and the large intestine (~5 ft long) where closely compacted cells form tight junctions and make up the gut lining, known as the intestinal epithelium. These cells are compact to ensure harmful bacteria, toxins and undigested food particles don’t make their way into the bloodstream. A healthy microbiota supports the mucosal barrier of the gut by scavenging for foreign pathogens, modulating the immune system, synthesizing certain vitamins and amino acids (including the B vitamins and vitamin K), and interacting with the gut-brain axis (1)(2)(3). The gut microbiome has even been shown to regulate brain chemicals, such as BDNF, which are proteins that promote the survival of nerve cells (neurons) (4).   

Leaky Gut and the Relationship to Cognitive Decline 

The term leaky gut, also known as increased intestinal permeability, has become an increasingly important topic within the health and nutrition space. Although all humans have a certain extent of intestinal permeability to regulate nutrient and water entry, evidence indicates that the western diet (a diet high in saturated fats and sugar and low in fiber)(5) in addition to heavy alcohol, stress and lack of sleep (6)(7)(8), can disrupt the gut lining and create gaps in these tight junctions. High amounts of gluten, in addition to bacterial overgrowth, has shown to elevate levels of a protein called zonulin that can also increase intestinal permeability (9). 

This increase in permeability allows certain harmful molecules, such as lipopolysaccharides (LPS), to “leak” into the bloodstream, which can trigger inflammation, cause changes within the gut microbiome (dysbiosis), and ultimately, lead to problems outside of the gut, such as neuroinflammation (10)(11). It has been shown that mice maintained on a western diet for 4 weeks exhibited ~3-fold increase in circulating LPS levels and increased intestinal permeability (12). This widespread inflammation can lead to the breakdown of the blood brain barrier (BBB) which permits these harmful substances to reach the brain and contribute to the progression of neurodegeneration (13). The BBB serves as protection for the brain and central nervous system by shielding it from neurotoxic substances found circulating in the blood. It’s important to note that the magnitude of BBB damage and memory impairment depends on the duration of western diet exposure (14). Microbiota changes caused by a chronic consumption of the western diet has been shown to impair peripheral insulin sensitivity, which is linked to hippocampal dysfunction (15). This consistent dysbiosis of the gut microbiome can also disrupt the production of BDNF which reduces brain plasticity, neurogenesis and can ultimately contribute to the development of Alzheimer's disease (16). 

Supporting Gut Health

Although the link between leaky gut, diet and cognitive decline is still being researched, the data indicate that it is crucial for those predisposed or diagnosed with Alzheimer’s disease to support the health of their gut, and ultimately the microbiome that resides within it. A healthy microbiome results in stronger tight junctions and mucosal lining which keeps systemic inflammation low and supports the integrity of the BBB. To support brain health, it is crucial that we support the health of the microbiome in the following ways: 

  • Include more fibrous foods in the diet, such as deeply pigmented vegetables and fruits. 
  • Limit high amounts of gluten containing foods.
  • Incorporate more healthy fats such as omega-3, through extra virgin olive oil, flaxseeds, chia seeds and salmon. 
  • Avoid excess sugar, alcohol and saturated fat.
  • Incorporate a consistent exercise routine. 
  • Reduce stress through exercise, deep breathing and meditation.
  • Aim to get 8-9 hours of sleep every night.

If you have further questions regarding leaky gut or how you can promote a healthy 

microbiome, sign up for our Cognitive Health Program today! 


  1. van de Wouw M, Boehme M, Lyte JM, Wiley N, Strain C, O'Sullivan O, et al. Short-chain fatty acids: microbial metabolites that alleviate stress-induced brain–gut axis alterations. J Physiol. (2018) 596:4923–44. https://doi: 10.1113/JP276431
  2. Cryan JF, Dinan TG. Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nat Rev Neurosci. (2012) 13:701–12. doi: 10.1038/nrn3346 
  3. Erny D, De Angelis ALH, Jaitin D, Wieghofer P, Staszewski O, David E, et al. Host microbiota constantly control maturation and function of microglia in the CNS. Nat Neurosci. (2015) 18:965–77. doi: 10.1038/nn.4030
  4. Evrensel, A., & Ceylan, M. E. (2015). The Gut-Brain Axis: The Missing Link in Depression. Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology, 13(3), 239–244.
  5. Rohr, M. W., Narasimhulu, C. A., Rudeski-Rohr, T. A., & Parthasarathy, S. (2020). Negative Effects of a High-Fat Diet on Intestinal Permeability: A Review. Advances in nutrition (Bethesda, Md.), 11(1), 77–91.
  6. Purohit, V., Bode, J. C., Bode, C., Brenner, D. A., Choudhry, M. A., Hamilton, F., Kang, Y. J., Keshavarzian, A., Rao, R., Sartor, R. B., Swanson, C., & Turner, J. R. (2008). Alcohol, intestinal bacterial growth, intestinal permeability to endotoxin, and medical consequences: summary of a symposium. Alcohol (Fayetteville, N.Y.), 42(5), 349–361.
  7. Ilchmann-Diounou, H., & Menard, S. (2020). Psychological Stress, Intestinal Barrier Dysfunctions, and Autoimmune Disorders: An Overview. Frontiers in immunology, 11, 1823.
  8. Li, Y., Hao, Y., Fan, F., & Zhang, B. (2018). The Role of Microbiome in Insomnia, Circadian Disturbance and Depression. Frontiers in psychiatry, 9, 669.
  9. Fasano, A., Not, T., Wang, W., Uzzau, S., Berti, I., Tommasini, A., & Goldblum, S. E. (2000). Zonulin, a newly discovered modulator of intestinal permeability, and its expression in coeliac disease. Lancet (London, England), 355(9214), 1518–1519.
  10. Sartori, A. C., Vance, D. E., Slater, L. Z., & Crowe, M. (2012). The impact of inflammation on cognitive function in older adults: implications for healthcare practice and research. The Journal of neuroscience nursing : journal of the American Association of Neuroscience Nurses, 44(4), 206–217.
  11. Ciccia, F., Guggino, G., Rizzo, A., Alessandro, R., Luchetti, M. M., Milling, S., Saieva, L., Cypers, H., Stampone, T., Di Benedetto, P., Gabrielli, A., Fasano, A., Elewaut, D., & Triolo, G. (2017). Dysbiosis and zonulin upregulation alter gut epithelial and vascular barriers in patients with ankylosing spondylitis. Annals of the rheumatic diseases, 76(6), 1123–1132.
  12. Cani, P. D., Bibiloni, R., Knauf, C., Waget, A., Neyrinck, A. M., Delzenne, N. M., & Burcelin, R. (2008). Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes, 57(6), 1470–1481.
  13. Mu, Q., Kirby, J., Reilly, C. M., & Luo, X. M. (2017, May 23). Leaky Gut As a Danger Signal for Autoimmune Diseases. Frontiers in immunology.
  14. Hargrave, S. L., Davidson, T. L., Zheng, W., & Kinzig, K. P. (2016). Western diets induce blood-brain barrier leakage and alter spatial strategies in rats. Behavioral neuroscience, 130(1), 123–135.
  15. Davari, S., Talaei, S. A., Alaei, H., & Salami, M. (2013). Probiotics treatment improves diabetes-induced impairment of synaptic activity and cognitive function: behavioral and electrophysiological proofs for microbiome-gut-brain axis. Neuroscience, 240, 287–296.
  16. Bathina, S., & Das, U. N. (2015). Brain-derived neurotrophic factor and its clinical implications. Archives of medical science : AMS, 11(6), 1164–1178.