A Healthy Gut Barrier Protects Against Inflammation

By Lillian So Chan



Intestinal permeability, also known as “leaky gut,” has been linked to many inflammatory and autoimmune diseases. Why is a healthy gut barrier important in protecting against these diseases?

All body surfaces, such as skin and the gut wall, are lined by layers of protective epithelial cells, which are connected by cell-cell junctions. These junctions serve three main purposes:

  • Adhesion, to maintain tissue form and integrity
  • Acting as border barriers to control the passage of water, cells, molecules, ions, and pathogens across epithelial layers
  • Signaling, to receive and transmit cues that affect cell behavior and tissue functions

Healthy barrier function is crucial in maintaining a balanced state of homeostasis. Breaking or even slightly disturbing these barrier layers can lead to serious health consequences, including inflammation and infection.

Our gut wall epithelial layers are constantly challenged by foreign substances that pass through the intestine, such as food and drink, drugs, microorganisms, pathogens, and toxins.

A healthy gut environment is preserved because the tight junctions in the mucus gut wall effectively and selectively control what passes through the epithelial layers, keeping pathogens and toxins out while allowing nutrients to pass through.

The gut epithelial barrier can become permeable as a result of genetic predisposition, gut pathogens, and hyperglycemia (high blood glucose concentration). For example, IBD (inflammatory bowel disease, such as Crohn’s) involves both environmental factors (smoking, diet, exposure to pollutants) and a genetic predisposition involving mutations in about 100 genes associated with epithelial cells, barrier functions, and immunity.

A recent study of experimental depletion of one IBD susceptibility gene has led to decreased gut barrier function and promoted gut inflammation and IBD.

In another study, researchers demonstrated how pathogenic bacteria can induce gut barrier defects, translocate to lymph nodes and liver via blood circulation, and trigger systemic autoimmune disease lupus erythematosus.

Chronic high blood glucose concentration, which is common in obesity, diabetes, and other metabolic syndromes, also disrupts the gut barrier, leading to gut and system inflammation and infections.

Researchers reported that chronic hyperglycemia affects barrier functions through metabolic and gene transcriptional reprogramming in the gut epithelial cells, which is regulated by a glucose transporter. This results in increased translocation of pathogenic bacteria and bacterial parts, causing inflammation in the gut and other parts of the body.

Unrestricted passage of pathogens and cells across the epithelial layers occurs when the integrity of the cell-cell junctions is disrupted. By allowing the passing of antigens and pathogens into epithelial layers and blood circulation, defective and “leaky gut” barrier can both initiate and maintain inflammation and spread infection.



About the Author

Lillian So Chan is the founding editor of WellnessOptions, a print magazine and website, and author of the book WellnessOptions Guide to Health published by Penguin Books. With over thirty years of experience in journalism and editing, Lillian has established unique editorial directions for several award-winning publications. She has worked for Maclean’s, Canada's largest news magazine, and served as a Governor and Deputy Chairperson of the Board of Governors at the Simon Fraser University, British Columbia, Canada.

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Resources

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Manfredo Vieira, S, et al. “Translocation of a gut pathobiont drives autoimmunity in mice and humans,” Science, 09 Mar 2018, https://science.sciencemag.org/content/359/6380/1156.

Mohanan, V, et al. “C1orf106 is a colitis risk gene that regulates stability of epithelial adherens junctions.” Science, U.S. National Library of Medicine, 9 Mar. 2018, https://www.ncbi.nlm.nih.gov/pubmed/29420262.

Thaiss C A, et al. “Hyperglycemia drives intestinal barrier dysfunction and risk for enteric infection,” Science, 23 Mar. 2018, https://science.sciencemag.org/content/359/6382/1376.

Luissint A C, et al. “Inflammation and the Intestinal Barrier: Leukocyte-Epithelial Cell Interactions, Cell Junction Remodeling, and Mucosal Repair,” Gastroenterology, U.S. National Library of Medicine, Oct. 2016, https://www.ncbi.nlm.nih.gov/pubmed/27436072.

Khor, B, et al. “Genetics and pathogenesis of inflammatory bowel disease,” Nature, U.S. National Library of Medicine, 15 June 2011, https://www.ncbi.nlm.nih.gov/pubmed/21677747.