Your immune system is the group of cells and molecules that protect you from disease by monitoring our body and responding to any foreign (non-self) substances they perceive as threats, particularly infectious microbes. Your immune system has co-evolved along with your microbiome, not only to create defenses against pathogens, but also to develop tolerance for beneficial microbes. There is a mutualistic relationship between your immune system and your gut microbiota, regulating one another and cooperating to support each other highlighted by the fact that 70–80% of your immune cells are found in your gut.

The dialogue between your immune system and your microbiome begins at birth. As you grow, the microbiome shapes the development of your immune system, and the immune system shapes the composition of the microbiota. This communication and mutual regulation is maintained throughout life creating the foundation for healthy interaction between the gut and the immune system.

In normal conditions, the immune system promotes the growth of beneficial microbes and helps maintain a stable microbial community, while in return, a healthy microbiome produces molecular signals that support the development of immune cells and contribute to the fine tuning of immune responses. A healthy crosstalk between the gut and the immune system supports protective responses against pathogens, promotes tolerance to harmless microbes and their products, and helps maintain self-tolerance (the ability of your immune system to not react harmfully to your own body).


The intestinal wall is the primary interface between the gut and your body. It acts as a dynamic barrier that isolates your body from gut microbes but 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, 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 adjust their antimicrobial response to eliminate pathogenic infections, destroy infected cells, and influence the composition of the gut flora through pattern recognition receptors (PRRs). Proper PRR signaling is important for the maintenance of tolerance to good microbes, for the elimination of intestinal infections, and consequently, for the maintenance of a balanced microbiome.

Epithelial cells also respond to metabolites produced by the microbiome, such as short-chain fatty acids (SCFAs), polyamines, and amino acids. Many microbial metabolites cross the epithelial barrier and are absorbed into the blood, through which they can reach other tissues in our body. Microbial metabolites can influence the development, maturation, and function of circulating and tissue-resident immune cells in different organs, including the brain Through these metabolites, the microbiome is able to fine-tune immune responses throughout the body.

The barrier function of the intestinal wall is also maintained by immune cells. Healthy intestinal barrier function allows certain gut-derived molecules to get into the body, while keeping others out. This supports better immune and brain performance.