Gut Microbiome and the Immune System

The immune system is a complex biological system, with a critical mission: to defend the inside of the body from outsiders that could be harmful. Although it may seem that our digestive tract, or gut, is inside our bodies, in reality, the inside of this tract is outside our bodies.  Substances needed by the body must first be absorbed from the gut into our blood and tissues. Absorption of nutrients that provide energy largely takes place quickly in the small intestine whereas the activity in the large intestine goes on for 10 to 24 hours and has to do with the microbiome, including its interaction with the immune system.

The mucin of the inner lining of the large intestine is the interface and barrier between the inside and outside of the body. This interface controls access to the blood and protects the inside of the body from pathogens ingested and passing through the gut. It is no surprise that the gut is one of the most active areas of the immune system—70-80% of the body’s immune cell interactions are in the GI tract.

GI immune response and the microbiome

 If we ingest pathogens, the GI immune system must recognize these pathogens and try to rid the body of them. It also must recognize and refrain from attacking microorganisms that live peacefully within us.

In a healthy gut, the majority of microorganisms are peaceful and even healthful.  While some microbes are always pathogenic, others can be beneficial under many conditions but harmful under others.  Given enough of the right nutrients, some bacteria produce important metabolites and signals. Formerly safe bacteria can become actively infectious or toxic, and some can stop producing metabolites that the body needs.

In general, outside of specific infectious diseases, it is not just the presence of a particular microorganism, but the absence of some types that can lead to problems.  And sometimes our immune system can be over-active or under-active based on the presence or absence of groups of gut bacteria.


Recognizing friend from foe

The immune system is usually quite good at recognizing friend from foe—distinguishing helpful from pathogenic. It needs to be on alert when it comes to pathogens, and it must be relaxed when it comes to friends.

To do this, the immune system must detect and sort the microbes in the folds and micro-crevices in the lining of the intestine. It is trained to do this from early in life. Microbiota are involved from the beginning—even while the fetus is still in the womb.  The first microbes received are from the mother, but soon after birth, others from the environment take up their places in the gut, and as they do so, train the immune system. The immune system appears to undergo critical training from birth to about 3 years of age. Babies and children who are not exposed to as many different types of microbes tend to end up with less developed immune systems, resulting in more allergies and autoimmune disorders.  Exposure to early daycare, lots of siblings, pets or farm animals helps children grow up with fewer allergies, through better training of the immune system by the “germs” present in less hygienic environments.  It seems that the more the immune system is exposed to early in life, the better it is able to detect  pathogens but leave harmless microbes (or substances) alone. Those healthful microbes can live in the gut and help keep the immune system ready to recognize friend from foe.

Microbiome and the intestinal lining

The intestinal lining serves as the barrier between the microbes inside our gut and our blood and tissues.  If the lining is broken or “leaky”, microorganisms and substances can leak into the blood vessels adjacent to the gut and enter our body.  Bacteria that are normally harmless members of our microbiome can trigger an autoimmune disease state when they get through the gut lining and enter tissues.

When foreign substances enter the body, the immune system mounts an inflammatory response where elements of the immune system flood into the area leading to painful swelling. Think of what happens to your skin when you cut or scrape yourself—it becomes hot, red, swollen, and sensitive to touch.  Acute inflammation like this is healthy, normal, and temporary. However, when inflammation of a large area lingers or steadily gets worse, the response is known as chronic inflammation.  Scientists are increasingly seeing chronic inflammation as  a key component of a number of health conditions, including obesity, inflammatory bowel disease, asthma, and arthritis.  Even cancer has been linked to chronic inflammation.

Healthful bacteria can help to maintain the  gut lining to prevent inflammation and can help inform immune system responses. An antibody called secretory immunoglobulin A (sIgA) is secreted by immune cells into the gut, where it acts as a first line of defense against toxins and pathogens.  SIgA works to clear unwanted intruders by entrapping them in mucus, blocking their entrance to the body tissues, and helping the mechanisms to push them out of the gut. Consuming the prebiotic beta-glucan from healthy foods like oats increases the secretion of sIgA into the gut and thus primes the immune system.

The health of the gut lining and of the microbes in the large intestine is critical .  If the microbes are not fed, they can eat the mucosal lining.  Such a hole in the protective layer leads to too many bacteria being presented to the immune system—even the entry of these bacteria into the circulatory system.

And what about the over-use of some therapies and long-term fasting. Over-use of treatments like antibiotics and immune suppressors can cause problems for the body’s microbiome and immune system. Supplementing  our diet with prebiotics leads to microbiome health and a host of benefits, including maintaining the integrity of the mucin layer.  Prebiotics are increasingly recognized for their ability to bolster the health of the microbiome in the large intestine, and thus help keep your immune system in tune.


References and Further Reading

Dysbiosis of the gut microbiota in disease. Carding S, Verbeke K, Vipond DT, Corfe BM, Owen LJ. Microb Ecol Health Dis. 2015 Feb 2;26:26191.


The human microbiome and autoimmunity. Proal AD, Albert PJ, Marshall TG. Curr Opin Rheumatol. 2013 Mar;25(2):234-40.


Translocation of a gut pathobiont drives autoimmunity in mice and humans. Manfredo Vieira S, Hiltensperger M, Kumar V, Zegarra-Ruiz D, Dehner C, Khan N, Costa FRC, Tiniakou E, Greiling T, Ruff W, Barbieri A, Kriegel C, Mehta SS, Knight JR, Jain D, Goodman AL, Kriegel MA. Science. 2018 Mar 9;359(6380):1156-1161.


National Cancer Institute: chronic inflammation and cancer


BioCentury Innovations.  GI Band-Aid.  April 2018.  by Michael Leviten


Obesity and inflammation: the linking mechanism and the complications. Ellulu MS, Patimah I, Khaza’ai H, Rahmat A, Abed Y. Archives of Medical Science : AMS. 2017;13(4):851-863.


The Influence of the Microbiome on Type 1 Diabetes. Paun A, Yau C, Danska JS. J Immunol. January 15, 2017, 198 (2) 590-595.


Type 2 diabetes and gut microbiome: at the intersection of known and unknown. Upadhyaya S, Banerjee G. Gut Microbes. 2015;6(2):85-92.


Early Development of the Gut Microbiota and Immune Health.  Francino MP. Pathogens. 2014;3(3):769-790.


Nutrient tasting and signaling mechanisms in the gut. II. The intestine as a sensory organ: neural, endocrine, and immune responses. Furness JB, Kunze WA, Clerc N. Am J Physiol. 1999 Nov;277(5 Pt 1): G922-8.


Published: May 24, 2018