Why Gut Bacteria Do Not Trigger an Immune Response

While it may seem paradoxical, the large population of gut bacteria does not trigger an immune response, yet they are capable of doing so. This article will explore why gut bacteria exist in our intestines without being eliminated by the immune system, the mechanisms behind this, and the co-evolution of humans and their microbiota.

Why Do Gut Bacteria Not Trigger an Immune Response?

The overwhelming supply of gut bacteria far surpasses the capacity of the immune system to eliminate them. In the mouth and colon, the bacterial density is around 10^10 per cubic centimeter, while in the stomach, gastric acid reduces this number significantly to around 10^4 in the duodenum, and motion in the small bowel keeps the count down to a manageable level. On a cellular count, there are more bacteria in the colon than there are cells in the body. Thus, the sheer volume of these microorganisms makes any immune response redundant.

Immune Tolerance and Regulatory Mechanisms

The lining of the intestines is densely populated with immune cells aimed at promoting immune tolerance. One of the most significant examples is the presence of regulatory T cells, which secrete immunosuppressive cytokines. Additionally, there is a thick mucous layer that prevents harmful bacteria from penetrating. If bacteria do cross this barrier, such as in the case of pathogenic bacteria, an immune response is triggered. However, the epithelial cells lining the intestines have a specific polarity. They possess TLR receptors on the basolateral side (the inner side not facing the intestinal cavity) that can sense bacteria and trigger an immune response. However, this does not occur on the apical side (the side facing the cavity), thereby maintaining a balance.

Normal Flora and Pathogenic Infections

Some bacteria that reside in the gut, known as normal flora, prevent more harmful bacteria from colonizing the gut. However, some of these bacteria can become opportunistic, causing infections under certain conditions. For instance, Escherichia coli (E. coli) is a normal gut flora and typically does not cause infections. However, it can cause urinary tract infections (UTIs) when it enters the urinary tract. Therefore, it is crucial to understand that maintaining a healthy balance of gut bacteria is essential for overall health.

Co-evolution and Homeostasis

Human beings and their microbiota have co-evolved to minimize the immune response to gut bacteria. The gut mucosa is lined with activated T regulatory cells that create an immunosuppressive environment against commensal bacteria and harmless food antigens. This is complemented by IgA-producing B cells that help control the access of commensal bacteria to the tissue. These bacteria mostly reside in the loose mucosa far from the epithelial barrier, avoiding immune responses and being expelled from the gastrointestinal tract. Understanding the balance between the host and the commensal bacteria is key to maintaining good health and preventing pathogenic infections.

Always remember, what is good for the host is also good for the commensal bacteria, and vice versa. Our bodies and gut bacteria share common interests in maintaining homeostatic conditions. This balance ensures that the microbiota remains beneficial and does not trigger an immune response in the intestines.