Gut Bacteria Remember Pathogens
New Discovery on Intestinal Immune System
Adds to the Complexity of the Human Body
by Jerry Bergman, PhD
To the proverb that nothing is certain but death and taxes can be added one other thing that is certain: as scientific research progresses, life will be shown to be increasingly more and more complex.
Another new discovery proves, once again, that this assertion is true. This new finding is that our intestinal track mucosa, besides all of its other jobs, was discovered to have yet another function. It is another part of the innate immune system that we are born with. Specifically, we know that it
plays a crucial role in regulating host-microbe interactions, and especially in providing protection against pathogens that invade the mucosa. Using an intestinal infection model, scientists discovered that innate effector cells — group 3 innate lymphoid cells — act not only during the early stages of infection but can also be trained to develop an innate form of immunological memory that can protect the host during reinfection.
The innate immune system engages in constant surveillance, providing early defense against pathogens very soon after infection. The adaptive immune system develops a “memory” for the pathogens encountered by activating certain receptors on the surface of B and T lymphocytes. Thus it adapts to the new threat to be able to rapidly and effectively destroy it. This process triggers the production of protective antibodies to defend against future infections. Research has now documented that the intestinal immune system also possesses this system.
The new system was discovered at the Pasteur Institute, named after Louis Pasteur, the creationist who worked hard to disprove abiogenesis. Escherichia coli (E. coli) are normal intestinal flora that rarely cause problems. These bacteria are present in drinking water and food, especially raw vegetables and undercooked ground beef. Many common strains of E. coli are found throughout the lower intestine of warm-blooded organisms. It is a Gram-negative, rod-shaped, facultative anaerobic (i.e., cannot live in an oxygen environment), coliform bacterium.
The Mutated Strains
Certain mutated strains of E. coli, called enteropathogenic and enterohemorrhagic Escherichia coli, can cause intestinal diseases or gastrointestinal bleeding. Their ingestion is responsible for nearly nine percent of all child deaths worldwide. Consequently, protection against these pathogenic strains, especially the most widely known O157:H7 mutant strain, is important to save lives. In healthy adults a O157:H7 infection can cause severe stomach cramps, bloody diarrhea, and vomiting, but children under two years old, as well as older adults, can develop a life-threatening form of kidney failure.
The Immune System
The intestinal track mucosa contains a complex defense system that enables it to combat pathogens while at the same time maintaining tolerance for the important commensal microbiota. Commensal microbiota are essential for normal bodily health. This constant surveillance is performed by the innate immune system, which provides early defense in the initial hours after infection.
Approximately 100 trillion microorganisms (mostly bacteria, but also some viruses, fungi, and protozoa) live in the human gastrointestinal tract. Collectively they are called the microbiome. The microbiome is so important that it functions as a virtual body organ. To ensure its health, supplements containing live bacteria called probiotics are often advised by adding foods such as yogurt to the diet.
Type 3 innate lymphoid cells (ILC3s) are abundant in the intestinal tract. These lymphoid cells are the innate counterparts of T cells. They contribute to immune defense by secreting locally acting hormone-like molecules called cytokines to coordinate the response to infections by other innate immune cells. The cytokine release activates the production of antimicrobial peptides by epithelial cells. The result is to reduce the bacterial load to help maintain the integrity of the intestinal barrier. They have important roles in mucosal homeostasis, host defense, and the organization of lymphoid tissues. The Pasteur Institute study found that
intestinal ILC3s persist for months in an activated state after exposure to Citrobacter rodentium. Upon rechallenge, these “trained” ILC3s proliferate, display enhanced interleukin-22 (IL-22) responses, and have a superior capacity to control infection compared with naïve ILC3s. Metabolic changes occur in C. rodentium–exposed ILC3s, but only trained ILC3s have an enhanced proliferative capacity that contributes to increased IL-22 production. Accordingly, a limited encounter with a pathogen can promote durable phenotypic and functional changes in intestinal ILC3s that contribute to long-term mucosal defense.
In other words, early exposure to certain pathogens results in “long-term” mucosal defense which argues for the view that normal exposure to many pathogens is necessary to produce the required protection. In the end, the body is understood to be even more complex and integrated than previously known.
The importance of the discovery that the innate mucosa immune system can be “trained” affects many areas of medicine. It paves the way for the development of ways to artificially strengthen the body’s defenses against a variety of pathogens, and yet allow the needed commensal bacteria to thrive. The discovery of a new antibacterial immune defense mechanism could also lead to novel therapeutic approaches to treat intestinal diseases and even some forms of cancer. The main immediate effect of this research is the reinforcement of the conviction that the enormously complex immune system is, in fact, much more complicated than anyone previously knew.
 Institut Pasteur, Discovery of an innate immunological memory in the intestine, press release, 28 February 2022, https://www.pasteur.fr/en/home/press-area/press-documents/discovery-innate-immunological-memory-intestine
 Institut Pasteur, 2022.
 Hartland, E.L., and J.M. Leong, Enteropathogenic and enterohemorrhagic E. coli: Ecology, pathogenesis, and evolution, Frontiers of Cellular and Infection Microbiology 3:15, 30 April 2013.
 Valdes, A., et al., Role of the gut microbiota in nutrition and health, British Medical Journal 361: :k2179. doi: 10.1136/bmj.k2179, https://www.bmj.com/content/361/bmj.k2179, 13 June 2018.
 Serafini, N., et al., Trained ILC3 responses promote intestinal defense, Science 375(6583):859-863, 24 February 2022.
 Serafini, et al., 2022.
Dr. Jerry Bergman has taught biology, genetics, chemistry, biochemistry, anthropology, geology, and microbiology for over 40 years at several colleges and universities including Bowling Green State University, Medical College of Ohio where he was a research associate in experimental pathology, and The University of Toledo. He is a graduate of the Medical College of Ohio, Wayne State University in Detroit, the University of Toledo, and Bowling Green State University. He has over 1,300 publications in 12 languages and 40 books and monographs. His books and textbooks that include chapters that he authored are in over 1,500 college libraries in 27 countries. So far over 80,000 copies of the 40 books and monographs that he has authored or co-authored are in print. For more articles by Dr Bergman, see his Author Profile.