The Gut-Brain Connection: How Leaky Gut May Contribute to Chronic Disease

In recent years, there has been a significant increase in cases of various diseases, including type 2 diabetes and inflammatory bowel disease, that are linked to imbalances in the gut microbiota. I have seen an explosion of conditions in my practice that results from damage to the gut lining. The gut is home to around 95% of the symbiotic microbes in the human body, which in a healthy state promote overall health. However, changes in diet, stress, chronic alcohol consumption, the use of antibiotics, and other environmental and genetic factors can alter the microbiota and lead to intestinal inflammation and increased intestinal permeability, a condition known as "leaky gut."

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Increased intestinal permeability has been shown to play a central role in the pathogenesis of inflammatory bowel disease (IBD), which includes Crohn's disease and ulcerative colitis. The intestinal epithelial barrier, which includes tight junctions between cells, helps to maintain the balance between tolerance and immunity to non-self antigens. The protein zonulin modulates these tight junctions, and when the zonulin pathway is deregulated, autoimmune, inflammatory, and neoplastic disorders can occur.

As the image below shows, when the lining of the gut becomes damaged, molecules make their way through the intestinal barrier that leads to the immune system having to respond aggressively.

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Fortunately, a dysbiotic microbiota can be improved with certain probiotics or by boosting the growth and metabolism of beneficial commensals in the colon with fiber-rich foods, especially targeting butyrate production. Butyrate, a cellular mediator, is produced by microbial fermentation in the large intestine and regulates multiple functions of gut cells and beyond, including gene expression, cell differentiation, gut tissue development, immune modulation, oxidative stress reduction, and diarrhea control.

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A polyphenol-rich diet, such as one that includes cocoa and green tea, has been shown to reduce intestinal permeability measures by inducing changes to the gut microbiota. Additionally, glutamine supplementation may be an effective treatment for patients with diarrhea-predominant irritable bowel syndrome (IBS-D) with intestinal hyperpermeability following an enteric infection. Studies have found that oral dietary glutamine supplements can safely and dramatically reduce major IBS-related symptoms.

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