There are numerous unanswered questions in modern medicine. What is aging, for example? Why do people become more inflamed as they age? What’s with all of the chronic, degenerative diseases? Why is lipid metabolism (LDL, HDL, triglycerides) linked to degenerative diseases, along with immune system function and inflammation? I am only going to start the answers here.
I might as well continue to be cryptic and give you the string of words/concepts I am trying to connect to answer the other questions:
Hydrogen sulfide (H2S), endorphins, hibernation, nuclear receptors (PPARs), antibiotics, chronic inflammatory diseases (fibromyalgia, arthritis, chronic fatigue, Lyme, Morgellon’s, Alzheimer’s, prostatitis, pancreatitis, cancers, etc.), autoimmunity, leaky gut/kidney/brain barrier, autism and H1N1.
First a word of advice: Beware of assuming that molecules are specific, i.e. with unique interactions, and that a small molecule will bind to one and only one protein target. [There are lots of bizarre exceptions to the assumption: Aldolase acts as a structural protein for Toxoplasma motility. Fluorescein is added to make protein fluorescent, but the fluorescein is also transported into cells on its own, i.e. fluorescein and rhodamine labeling can give different results. Heparin binds to most extracellular proteins and it is mostly a hydrophobic interaction -- heparin is not just for clotting anymore.]
Observations from the literature:
- Maternal autoimmunity is linked to autism.
- Autism is linked to leaky gut and chronic inflammation.
- Gut/kidney/brain barriers are based on integrity of extracellular matrix (heparan sulfate) that is compromised by inflammation.
- Chronic diseases require inflammation and circulating inflammatory cytokines (TNF, IL-1, IL-6) are elevated..
- NSAIDs induce leaky gut and release of bacteria toward liver.
- Phagocytosis of bacteria leads to transport of some bacteria, e.g. Chlamydia pneumoniae to other sites of inflammation, e.g. gut to joints.
- Opiods can induce hibernation in rodents.
- Sulfides can induce hibernation in rodents.
- H1N1 my cause lethal pneumonia by lung cytokine storm.
- Inflammatory cytokines and inflammation result from activation of NFkB.
- Hibernation involves PPARs (another nuclear receptor transcription factor).
- Omega-3 fatty acids reduce inflammation via COX-2 prostaglandins, but also by binding to PPARs.
- For most of the diseases under consideration, suppression of inflammation will eliminate symptoms.
- Antibiotics can impact all of these diseases in unpredictable ways. In some cases complete remission can be achieved and in other cases antibiotics can produce lethal cytokine storms.
- Bacterial cell wall components, e.g. lipopolysaccharide, lipid A, are intensely pyrogenic, i.e. inflammatory.
Cryptic Bacteria in our Tissues
The role of bacteria in numerous diseases, including cancers, has been proposed since the early isolation of bacteria from human tissues. Many of these bacteria are difficult to culture and have variable forms viewed by microscope. Because these bacteria are difficult for microbiologists to handle with conventional approaches, their existence and significance has always been questioned. Use of antibiotics to treat chronic, inflammatory conditions has seemed inconsistent with the unproven existence of a bacterial cause. Thus, there is surprise when the inappropriate use of antibiotics leads to a cure.
Cryptic Bacteria Suppress Local Inflammation and Promote Chronic Inflammation
I think that the fundamental problem is the assumption that human tissue is sterile, i.e. free from microorganisms, such as bacteria, unless there is overt infection. Part of the sterile assumption derives from the intense inflammatory response to bacteria. In order for bacteria to survive in tissue, the bacteria must suppress inflammation and the tissue must tolerate the slow leaching of inflammatory bacterial materials.
Chronic Disease Hypothesis
Based on the cryptic bacterial infection hypothesis, many, if not all chronic diseases are initiated by inflammatory events that release bacteria into the blood stream carried in phagocytic cells. The cells migrate and take up residence at a region of inflammation. The bacteria produce molecules that produce tissue hibernation and quell local inflammation in response to the bacteria. The bacteria are, however, a source of ongoing irritation to the tissue and a chronic inflammatory disease results.
Eradication of Cryptic Bacteria
Antibiotics would be a typical choice for killing infecting bacteria. In the case of cryptic, chronic infections, however, application of therapeutic antibiotics may be problematic. The established infections may have produced privileged locations isolated from the vascular system and protected by a bacterial community, e.g. a biofilm. Alternatively, the death of the bacteria and release of pyrogenic factors my produce life-threatening inflammation, that requires careful support.
Hibernation in Rodents Provides Treatment Clues
The compromise of tissue inflammation in response to cryptic bacteria is similar to the physiology of rodent hibernation. In both cases, systemic inflammation is suppressed. At the cellular level, this means that other signaling pathways silence the inflammatory NFkB expression pattern. One of the major nuclear receptors that is activated in hibernation is PPAR. PPAR is activated by opiods and H2S, which also induce hibernation in rodents. There are numerous analogs, inhibitors and H2S donors that could be used to disrupt hibernation (free local suppression of inflammation) or reduce symptoms by suppressing systemic inflammation.
Inflammation Compromises Tissue/Blood Barriers
Inflammation causes a disruption of the integrity of the endothelial extracellular matrix at sites of local inflammation. NFkB activation shuts down the expression of genes involved in heparan sulfate proteoglycan (HSPG) synthesis makes the tissue/blood barrier leaky. Locally this facilitates the recruitment of lymphocytes and neutrophils for defense, but systemically it leads to leaky gut/kidney/brain barriers that permit bacteria to cross.
Convergence of Therapies to Attack Cryptic Infections
The central approaches to attack cryptic infections are a combination of antibiotics and suppression of cytokine storms. These approaches are used in Marshall’s Protocol [http://bacteriality.com/ ], which also exploits a vitamin D receptor antagonist, Olmesartan, that also inhibits NFkB and inflammation.
A similar protocol has been developed by Dr. Michael Powell to inhibit hibernation and attack cryptic infections:
These approaches are similar to the lengthy use of antibiotics for the treatment of chronic Lyme disease.
It is very interesting to note that some of the most effective treatments for a long list of degenerative chronic diseases, autoimmune diseases and cancers, use essentially the same protocol that should attack cryptic bacteria and provide support for ensuing inflammation.