THE GUT BARRIER

by Don Pearson, Technical Director BioBrew Ltd

The intestinal wall is the interface between the gut microbiome and our body. It acts as a barrier that isolates our body from gut microbes. But it also allows desirable interactions to take place. The intestinal barrier is made up of physical and chemical elements. The physical barrier is created by the epithelial cells that line the gut. This includes the molecules on their surface, and the mucus they produce. The chemical barrier is created by inflammatory molecules (cytokines), antibodies, and antimicrobial substances produced by epithelial and immune cells.

Epithelial cells can recognise some microbial products via immune receptors known as pattern-recognition receptors (PRRs) (Pott & Hornef, 2012). Activation of these PRRs enables epithelial activity to be adjusted based on chemical signals from the gut microbes. This means that epithelial cells can change their antimicrobial response to eliminate pathogenic infections, destroy infected cells, and, in turn, influence the composition of the gut flora. Appropriate PRR signalling is important to maintain tolerance to good microbes, for the elimination of intestinal infections, and consequently, for the maintenance of a balanced gut microbiota (Fawkner-Corbett et. al. 2017).

Epithelial cells also respond to metabolites produced by the gut microbiota. This includes short-chain fatty acids (SCFAs), polyamines, and amino acids. SCFAs serve as energy sources for epithelial cells. They help to modulate their metabolism and secretions. SCFAs also help support the integrity of the epithelial barrier (Thaiss et. al. 2016).

Many microbial metabolites, usually relatively small molecules, cross the epithelial barrier and are absorbed into the blood. Through this path they can reach other tissues in our body. Microbial metabolites can influence the maturation, development, and function of immune cells in different organs, including the brain. Through these metabolites, the gut microbiome is able to influence the innate immune responses throughout the body (Thaiss et. al. 2016).

The barrier function of the intestinal wall is enhanced by immune cells. For example, dendritic cells, whose extensions protrude from between epithelial cells into the intestinal lumen, probe the microbiota environment, sensing potential threats and reacting directly or through lymphocyte cells. Lymphocyte cells located in the intestinal wall participate in adaptive immune responses that contribute to the maintenance of the epithelial barrier. They can also suppress responses to harmless microbes helping to promote immune homeostasis (Honda and Littman, 2016).

Summary

A healthy intestinal barrier allows certain gut-derived molecules to get into the body, while keeping others out. This helps support better immune and brain performance.

Fawkner-Corbett D, Simmons A, Parikh K. (2017) Microbiome, pattern recognition receptor function in health and inflammation. Best Pract Res Clin Gastroenterol. 2017 Dec;31(6):683-691. doi: 10.1016/j.bpg.2017.11.001.