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The gut barrier – first line of defense

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Dialogue between the gut and the immune system

The digestive system has been called the primary immune defense system as it is the central channel between the external environment and the internal systems of our body. It also has a central role in regulating immune homeostasis (1).

In fact, the gut is one of the most important aspects of immunity, as 70–80% of the body’s immune cells are found in the gut. 

The gut barrier – First line of defense

The intestine’s surface is built from a single layer of epithelial cells surveying as the first line of defence against exogenous invasion and the primary interface between intestinal bacteria and our body. Its semipermeable structure allows the uptake of essential nutrients while being an effective barrier to protect against the invasion of pathogenic microorganisms and passage of potential harmful macromolecules into the body. It also maintains intestinal mucosal immune homeostasis.

The structure and permeability of the epithelial layer is known to be modulated by a variety of factors, including factors such as smoking, diet, alcohol, medications and exposure to pollutants (2).

Disruption of the gut barrier has been associated with various pathological conditions in the GI tract and other body organs. Therefore, the maintenance of a healthy intestinal barrier is essential to our general health.

Gut barrier function

The gut barrier operates via a system that includes physical and biological barriers [3].

The physical barrier is composed of gut microbiota, mucus which contains antimicrobial compounds and antibodies, epithelial and immune cells. 

The mucus layer consists of gel produced by epithelial cells.  The mucus protects the epithelial cells layer from digestive enzymes, prevents a direct contact of microorganisms and large molecules with the cells beneath while allowing small molecules to pass. 

The gut contains trillions of bacteria with over 1000 species, including commensal and pathogenic bacteria, which compete on space and energy resources. The balance between the beneficial and harmful bacteria maintain the mucosal integrity and modulates the immunological activity of the gut barrier.

The composition of the mucus layer can affect the microbiota in the gut, whilst the microbiota also determine the properties of the mucus gel. 

The biological barrier includes antimicrobial peptides, such as beta-defensin-2 immune mediators, and small signalling proteins, such as cytokines and chemokines, which recruit and regulate the differentiation and activation of immune cells [4].

Defensins are antimicrobial peptides (natural antibiotics) expressed by epithelial cells in the gut. They are essential components of the intestinal lumen and play a crucial role in defending the intestine (and thus the rest of the body) from bacterial pathogens. Beta-defensin-2 kills pathogenic bacteria in the gut by damaging their protective cell wall. In addition to its direct effect on the pathogenic bacteria, beta-defensin-2 was shown to induce the production of mucin molecules, which are an essential part of the mucosal lining of the gut and serve as part of the intestinal barrier[5].

SCFAs: the link between Gut microbiota and the immune system

Short-chain fatty acids produced by bacterial fermentation in the gut serve as a link between the microbiota and the immune system. The main SCFAs include Acetate, Propionate, and Butyrate. SCFAs are an important energy source for the gut’s epithelial cells and are essential for regulating the cellular functioning and turnover of the intestinal barrier. Many microbial metabolites cross the epithelial barrier into the bloodstream to other body tissues, where they influence the development, maturation, and function of immune cells, including neutrophil macrophages and T-lymphocytes (immune cells that kill pathogens) in different organs[6].

Prebiotics to increase gut health

There are many ways to support the composition of the beneficial gut microbiome, and one of the easiest is through the use of dietary supplements. Prebiotics are dietary compounds that induce the growth or activity of beneficial microorganisms. 

Bioecolians, an alpha-gluco-oligosaccharide, is an effective, unique prebiotic, active at low doses, providing proven health benefits with only 2g/day.
Thanks to its unique chemical structure, Bioecolians is stable in low pH. Therefore, it is not broken down in the stomach and small intestine and reaches the large intestine fully intact. In addition, it is fermented by colonic bacteria, allowing the large intestine’s microbiome to flourish.

Studies with Bioecolians have shown that it promotes the growth of beneficial bacterial strains such as lactobacillus and  bifidobacterial, it stimulates the production of SCFA’s and beta-defensin-2 and improves symptoms such as abdominal pain, bloating, fecal frequency and consistency in subjects suffering from irritable bowel syndrome with constipation (7)

 

References:

  1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5788425/
  2. Susana Lechuga, Disruption of the epithelial barrier during intestinal inflammation: quest for new molecules and mechanisms. Biochim Biophys Acta. 2017 July;1864(7): 1183–1194
  3. den Besten G, van Eunen K, Groen AK, Venema K, Reijngoud DJ, Bakker BM.                The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism. J Lipid Res 2013; 54: 2325–2340
  4. C.A. Thaiss, N. Zmora, M. Levy, E. Elinav, Nature 535 (2016) 65–74.
  5. Jan-Michel Otte, Human Beta defensin 2 promotes intestinal wound healing in vitro, Journal of cellular biochemistry 104, 2286-2297 (2008)
  6. Renan Oliveira Corrêa Regulation of immune cell function by short-chain fatty acids. Clinical & Translational Immunology (2016) 5, e73
  7. Yvergnaux Florent, Lassalle Laurent*, Saguet Thibaut The Effect of Bioecolians, A Commercial α-Gluco-Oligosaccharide, on Bowel Function in Subjects with IBS-C Symptoms Jou