The gut barrier
The inside of the gut (the ‘lumen’) is separated from the rest of our body by a single layer of cells. This layer is the intestinal epithelium. Because of its importance, the complete intestinal epithelium is renewed every 3–5 days, to remove damaged cells. To explain further, the space between the cells of the gut epithelium is sealed by tight junctions. These tight junctions regulate the permeability of the gut barrier. They prevent the passage of large molecules through the epithelium. At the same time, they allow ions, water, and small compounds to pass. But to be efficient, these proteins have to be expressed at an optimal level and have to be correctly located in the cells. If the expression or location of these proteins is altered, the gut barrier function is impaired.
A second key component of the gut barrier function is the mucus layer covering the intestinal epithelium. This mucus layer is produced by specific cells of the intestinal epithelium, called Goblet cells. The mucus layer protects the gut against mechanic damage, but also against penetration by microorganisms. To sum up, if the thickness of the mucus layer decreases, the gut barrier is compromised.
The third key component of the gut barrier is antimicrobial peptides produced by Paneth cells. Indeed, the intestinal epithelium produces and secretes many different antimicrobial peptides and proteins (AMPs) in the lumen. The AMPs help in the defence against microorganisms. For instance, these AMPs strengthen the mucus layer by killing bacteria close to the epithelium or inhibiting their growth.
Root causes of disease: disruption of the gut barrier
The gut barrier manages what comes in and goes out in the gut. To clarify, we call gut ‘permeability’ the flow rate of molecules across the gut epithelium. When the function of the gut barrier is disturbed, the gut permeability will increase. This means that more components pass from the gut lumen in the human body. Most importantly, a balanced and diverse gut microbiota is needed for the development, maintenance, and optimal function of the gut barrier. Indeed, when the human microbiota is challenged with changes in diet, stress, antibiotics or diseases, its composition undergoes changes. It leads to a dysregulation of the gut microbiota composition and functions. This dysregulation is called dysbiosis.
Consequently, dysbiosis of the gut microbiota impacts the functioning of the gut barrier. Indeed, it leads to increased intestinal permeability. This then allows gut content such as bacterial metabolites and molecules, as well as bacteria themselves, to leak through the gut barrier and into the systemic circulation. In fact, increased epithelial permeability in the gut is also called ‘leaky gut’. Inflammatory stimuli can increase permeability of the epithelium via altered tight junction protein composition or dynamics. When gut permeability is increased, pro-inflammatory toxins (for example lipopolysaccharides – LPS) can enter the bloodstream. Finally, it leads to chronic low-grade inflammation (a low-level of inflammation but which lasts a long time) throughout the body (e.g., in the liver and adipose tissues).
In addition, increased intestinal epithelial permeability (leaky gut) is associated with a variety of gastrointestinal disorders. They include inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), celiac disease, and the early stages of colon cancer development. Moreover, altered intestinal epithelial permeability is also associated with numerous extra-intestinal disorders such as obesity, type-2 and type-1 diabetes, neurological disorders and food allergy.
- Cani PD. 2018 Hope, threats and promises https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6109275/pdf/gutjnl-2018-316723.pdf
- Paone P. and Cani PD. 2020 Mucus barrier, mucins and gut microbiota: the expected slimy partners? https://gut.bmj.com/content/gutjnl/69/12/2232.full.pdf