The Microbiota and the Immune System
Being the largest interface between the body and the external environment, it is not surprising that the gastrointestinal tract (GIT) is tightly associated and constantly in communication with the immune system. Intestinal bacteria develop and regulate the host immune system and the immune system affects the composition of the intestinal microbiome . In particular, the host immune system is responsible for ensuring a beneficial microbiota composition controlling specific bacteria overgrowth, but also reacting to pathogenic bacteria or molecules meeting with the intestinal barrier. In particular, the host immune system is responsible for ensuring a beneficial microbiota composition controlling specific bacteria overgrowth, but also reacting to pathogenic bacteria or molecules meeting with the intestinal barrier . The interaction between immune system and pathogens is also regulated by microorganisms that can directly interact with pathogenic bacteria or indirectly stimulate the immune system to do the same. Gut homeostasis is therefore reached and maintained when the immune system establishes an appropriate balance between tolerance to commensal (not harmful), mutualistic (beneficial), and opportunistic (pathogenic) bacteria . This balance is consolidated only when the immune system can communicate with the gut microbiota and a key player in this cross-talk process is a healthy intestinal barrier.
Bacteria with Antimicrobial Properties
Specific bacteria strains have been described to have antimicrobial properties usually associated with secretion of peptides or molecules which enables them to compete within the complex gut ecosystems. These molecules may protect the host against infectious bacteria and favor the survival of commensal bacteria .
Toxin-antitoxin (TA) systems are prevalent in bacteria. we present a review of the TA systems described to date and their biological role in human pathogens belonging to the ESKAPE group (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.) and others of clinical relevance (Escherichia coli, Burkholderia spp., Streptococcus spp. and Mycobacterium tuberculosis). These species releaase toxins when alive and/or when dead.
Basically, what appears to be happening is that most patients have the wrong bacteria in their gut and/or gut permeability control has been lost. This results in unhealthy metabolites (“toxins”) from gut bacteria entering into circulation. In fact, research has shown that up to one-third of the small molecules in the blood come from bacteria in the gut. Worse, however, is when a patient has overgrowth of particularly unhealthy bacteria, especially Gram-negative, the absorbed lipo-polysaccharides (LPS) are highly toxic with blood levels correlating with many chronic diseases.
According to Wikipedia, endotoxin is defined as “any toxin secreted by a microorganism and released into the surrounding environment only when it dies.” Technically in the research literature, only bacterial LPS are considered “endotoxins.” LPS are the most studied and considered prototypic activators of innate immunity by gut bacterial products. These LPS represent 80% of the cell-wall mass of Gram-negative gut bacteria.
Here we use the more clinically relevant broader definition of endotoxin as “any metabolite or cell wall constituent released by gut bacteria that damages human physiology,” because a surprising 25% to 33% of the small molecules in human blood can be derived from gut bacteria. The effects of LPS and the many other endotoxins from gut bacteria cause substantive and diverse physiological dysfunctions. When endotoxins reach a high enough level in the blood, a threshold is reached called metabolic endotoxemia. Once this threshold is reached, several strong, dose-dependent disease associations become apparent. There are many reasons for the increased levels of endotoxins seen in modern civilizations. Less obvious, perhaps, is stomach acid secretion suppression by proton-pump inhibitors and H2 blockers. The research is very clear that the use of these agents results in increased colonization of the gut by Clostridium difficile, thus substantially increasing the release and absorption of LPS.