Can our gut microbiome have an effect on our immune system?
What is the gut microbiome?
The microbiome is a collective term for the microorganisms that reside and colonize in certain body parts such as the gut, skin, and mucosal environments. The microbiome comprises mainly of the microbes belonging to several bacteria, viruses, parasites, and fungi. In our gut, there is a wide variety of these microorganisms involved in the digestion process and inhibit the colonization of pathogens. The healthy and normal human gut microbiota has two major phyla, namely Bacteroidetes and Firmicutes.
What is the interaction between the gut microbiome and our immune system?
Our body, under normal and healthy conditions, has a properly functioning immune system that helps maintain a balance between the existing microbiome and at the same time fights to keep the disease-causing microbes at bay. The microbiome resides peacefully in the gut mucosa; however, it is also responsible for invoking immune responses that help the intestinal epithelial cells to create a barrier to the pathogens.
The single-celled intestinal epithelial layer is a perfect barrier against pathogenic microorganisms. Proper communication between the gut microbiome and the immune system helps modulate immune responses against the attack of pathogens.
How does the gut microbiome communicate with the immune system?
There appears to be a communication network between the gut microbiome and the immune system on a platform provided by the intestinal epithelial cell wall. Figure 1- Interactions to control the intestinal homeostasis explains that this communication is a three-way communication that involves the gut microbiome, the mucosal immune cells, and the intestinal epithelial cells.
Figure 1: Interactions to control the intestinal homeostasis
(Source: Goto Y, Kiyono H. Epithelial barrier: an interface for the cross-communication between gut flora and immune system. Immunol Rev. 2012 Jan;245(1):147-63. doi: 10.1111/j.1600-065X.2011.01078.x. )
The communication takes place as follows:
- The three-way communication provides a flexible and dynamic environment for maintaining a balance between active and quiescent immunity of our body.
- The gut microbiome modulates the immune responses in the mucus cells and influences the multiple epithelial functions by the production of cytokines such as TNF (Tumor Necrosis Factor), IL-6, and lymphotoxin. This results in the formation of secondary lymphoid tissues and a physiological inflammation capable of fighting the invading antigens, which is a temporary phenomenon.
- Sometimes, certain genetic conditions or some pathogenic species may cause permanent disruption of this epithelial cell wall. In such instances, there is chronic inflammation at the epithelial barrier due to sustained invoking of the immune responses by the microbiome. Such conditions may give rise to inflammatory diseases such as irritable bowel disease (IBD), Crohn’s disease, or ulcerative colitis. Therefore, prebiotics like LactobacillusGG, Lactobacillus plantarum, L acidophilus, Lactobacillus casei, and Bifidobacterium animalis are often taken to reduce the inflammation in the colon.
At the glycoprotein level, it has been recently observed that the P-glycoprotein (P-gp) plays a fundamental role in balancing the immune responses modulated by the gut microbiome, especially the Clostridia and Bacilli class. The expression of P-gp in healthy individuals also explains that it maintains the physical barrier posed by the intestinal epithelial cells. Studies suggest that in inflammatory diseases, there is an under expression of P-gp, and at the same time, there is an imbalance in the gut microbiome. Further research proves a link between the gut microbiome expressing the P-gp, critical for intestinal homeostasis. Short-chain fatty acids and bile salts also play a vital role in this.
The processes in the gut microbiome also affect the immunity in the extraintestinal regions of our body, including the brain, through the functional gut-brain axis pathways. This is how the gut microbiome can communicate with the intestinal immune system and with our entire body’s immune system through the epithelial wall of the intestine.
Conclusively, the gut microbiome uses P-gp as communicators to carry out proper communication with our immune system. Hence, genetic diseases, the antibiotic treatment that affects the gut microbiome, dietary changes that challenge the existing microflora result in inflammatory conditions that are responses of our immune system. This provides an opportunity for specific dietary products or medicines targeted to the gut microbiome to maintain immune homeostasis.
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