Essential Oils, Phytoalexins, Drugs Are All Antibiotics

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Superbug multidrug resistant plasmid

A recent, informative article by Tori Rodriguez for The Atlantic suggests that,

Essential Oils Might Be the New Antibiotics.

I want to discuss other ramifications of using essential oils as antibiotics to avoid multiple antibiotic resistant superbugs.

The logic for using essential oils in place of medical antibiotics is compelling: 

• Essential oils are extracts of plants, which have myriad traditional uses, including food.
• Most antibiotic use is to increase livestock production. 
• Antibiotics selectively kill gut bacteria in livestock and make them obese.
• Antibiotic resistance occurs within a week of use in livestock (or people.)
• Medical antibiotics are quickly losing efficacy.
• Antibiotic resistance genes quickly move from agriculture to superbugs to people.
• Plants/essential oils contain natural antibiotics that kill gut flora and increase livestock productivity.
• Resistance to essential oil antibiotic activity is slower, because of simultaneous use of multiple antibiotics.

Obesity is a Symptom of Antibiotic Damage to Gut Microbiome

Antibiotics make meat fatter

We may enjoy a fat marbled steak, but the corn and antibiotics used to produce that mouth-watering plate of satiety, is not so healthy.  Corn and antibiotics make that meat on the hoof fit for human consumption, but the cattle are quickly dying and the fat marbling is a symptom of cattle metabolic syndrome.  The corn and antibiotics disrupt the bovine gut microbiota and alter energy flow.  The result is prime beef. 

As It Is with Cattle, so It Is with Middle Americans

General descriptions of Americans with metabolic syndrome and steers ready for the abattoir are similar.  That should not be surprising, because both are caused by damaged gut microbiota and consequences of metabolic syndrome.  Americans routinely damage their gut microbiota with antibiotics (processed food, etc.) and the major symptoms of the resulting gut dysbiosis are chronic inflammation, depression, autoimmune diseases, obesity and metabolic syndrome.  Repairing gut microbiota reverses all of these symptoms. 

But Essential Oils Are Just Natural Antibiotics

Essential oils are natural antibiotics

Is it better to use essential oils than medical antibiotics to fatten cattle or treat Lyme disease or hospital infections such as C. diff.?  Most pharmaceuticals were derived from plants or fungi and were originally used to kill microorganisms, i.e. they were natural antibiotics.  We call these phytochemicals by a variety of names, e.g. antioxidants or essential oils, but they are more appropriately called phytoalexins, all natural, all plant, all toxic antibiotics.  It is entertaining that essential oils have had so many different traditional and pharmaceutical uses, and yet they have always been experienced by microorganisms (and our livers) as simply toxic.  Essential oils do have the significant advantage of being a mixture of antibiotics and might be very useful where pharmaceutical antibiotics have problems.  The toxicity of essential oils, especially toward gut bacteria, should not be ignored.

Resistance to Essential Oils as Antibiotics

Antibiotic resistance develops in sewage

I previously kept track of laboratory strains of bacteria by simply exposing large numbers of the bacteria to an antibiotic and selecting for the rare individual that had already spontaneous mutated (DNA replication error of one in a million).  We could then use the new drug resistant strain in experiments and identify it by its resistance.  The same thing happens to your gut bacteria with an overnight exposure to an antibiotic.  And of course it also occurs immediately in livestock exposed to antibiotics or in sewage plants where tons of antibiotics and gut bacteria are mixed.  Resistance to each of the chemicals in an essential oil also would rapidly occur, if bacteria were exposed to each alone and in a  toxic concentration.  This is repeatedly observed, since commonly used drugs are just individual components of essential oils that have been produced in large amounts in pills and marketed based on their predominant physiological activity, rather than just another antibiotic.  Thus, resistance to a statin or Metformin, as antibiotics, could be easily observed (even on multiple drug resistance plasmids), but is just ignored.

Essential Oils Are just Mixtures of Natural Antibiotics

Statins from fungal antibiotics

The impact of essential oils on gut microbiota is unpredictable, because the composition of essential oils is highly dynamic and so are gut microbiota.  Each component of an essential oil has a different spectrum of toxicities to hundreds of different target proteins to each of the hundreds of different species of bacteria in the human gut.  Ingested essential oils are modified by the detox enzymes of the intestine and liver.  The modified phytochemicals have different toxicities and act as additional antibiotics.  Mixtures of antibiotics, as in essential oils, less likely to select for resistance than individual antibiotics, but an antibiotic is still just an antibiotic, regardless of whether it is straight from the plant or via a pharmaceutical salesman. 

Common Medicines Are the Source of Superbugs

Common meds are antibiotics

Doctors with prescription pads and steers eating antibiotics are blamed, I think unjustly, for the crisis of antibiotic resistance.  The real culprit is you taking NSAIDs, statins, proton pump inhibitors, antidepressants and other common medicines.  Since they are all developed from plant antibiotics, they are still antibiotics, and they still select for antibiotic resistance.  It is important to remember that pharmaceuticals are repurposed natural antibiotics from plants.  The answer to the superbugs that are resistant to all of the common antibiotics is to dramatically reduce the use of all pharmaceuticals.  The initial goal should be a 90% reduction.  Costly pharmaceutical chemicals could be replaced with preventive diets and less disruptive manipulations of gut microbiota, e.g. ingestion of capsules containing freeze-dried gut flora.  This more gentle approach to health care would also provide huge cost savings, as well as vastly improving health.

Antibiotics, Gluten, Hashimoto's Thyroiditis and Baldness

My impression is that Hashimoto's is caused by a combination of an initial immune attack on the thyroid and incompetent regulatory T cells.  In most cases the immune attack on the thyroid is a secondary consequence of celiac/gluten intolerance, in which anti-transglutaminase antibodies attack transglutaminase bound to gluten in the intestines.  Transglutaminase  is an enzyme that is also produced by the thyroid (and hair follicles) and attack by celiac antibodies can enhance or inhibit thyroid hormone production (or baldness.)  Both Hashimoto's and celiac do not occur if the suppressive part of the immune system, i.e. regulatory T cells, is functioning.  

Antibiotics Compromise the Immune System

The major point here is that antibiotics disrupt normal bacterial biofilms that line the intestines and these healthy gut bacteria are required for development of regulatory T cells.  Compromise of Tregs leads to autoimmune diseases, e.g. celiac, Hashimoto’s and baldness, and also allergies.

Antigens/Allergens Have Basic Amino Acid Triplets

The antigens targeted in autoimmune diseases, e.g. tTG, anti-nuclear, TPO, and allergies form an obvious pattern.  All of these antigens and allergens have simple amino acid sequences (rare patches of three basic/positively charged amino acids) that enhance their presentation to the immune system to produce antibodies.  Nuclear proteins, for example, are frequent autoantigens and most of these proteins interact with nucleic acids (negatively charged) and have predictable patches of positively charged amino acids (arginine and lysine).  Other common autoantigens have basic amino acid (arg/lys) patches, because they interact with phospholipids (also negatively charged.)  Proteins with basic patches, e.g. HIV-TAT or heparanase, are also readily transported into cells and nuclei.  Peptides with these sequences are produced by action of stomach enzymes on proteins, e.g. milk lactoferrin, and are antimicrobial.

Allergies / Autoimmune Diseases Are a Predictable Consequence of Antibiotics

Doctors treat with antibiotics, but they fail to repair damage that they cause to gut flora.  The gut flora of most patients treated with antibiotics, especially those who are most fastidiously hygienic, never fully recover.  Constipation is a common symptom of severe dysbiosis and related immunoincompetence.  Probiotics are gut flora bandaids and do not survive as components of gut flora.

Gut bacteria are also needed for development of the aggressive part of the immune system.  Thus, autoimmune diseases can be treated with even more intense use of antibiotics, that will eliminate the rest of the immune system.  Since all vitamins are produced by gut flora as quorum sensing signals, antibiotics can also produce the exotic symptoms of vitamin deficiencies.

Antibiotics are essential to many therapeutic approaches, e.g. surgical procedures or therapy for chronic Lyme disease, but they must be used responsibly and treated patients must be subsequently tested to ensure a repaired gut flora and a functional immune system have been reestablished after antibiotics.  Long term antibiotic use needs special attention, e.g. deliberate Repair of Gut Flora or a fecal transplant.

Thus, I think that it is most likely that ever increasing antibiotic exposure and processed foods, coupled with obsessive hygiene have led to crippled gut flora (as observed in the simplified gut microbiomes of Americans), a net decline in suppressive Tregs and the observed increase of autoimmunity and allergies.  The competence of the immune system may be a major determinant in the course of infection with a pathogen that can produce chronic infections.

Chronic Disease, Cryptic Infections, Hibernation

Suppression of Inflammation and Surviving Cytokine Storms

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:
http://www.faqs.org/patents/app/20090163448

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.

Lyme Spirochete Binds to Heparan in Blood Vessels

Borrelia burgdorferi Sticks to Host Cells via Heparin-binding Proteins

A research group at the University of Calgary has watched the binding of fluorescent Borrelia burgdorferi spirochetes, the Lyme disease pathogen, to the surface of blood vessels in mice. (ref. below) A small heparin molecule was shown to block this interaction between the spirochete surface protein BBK32 and the heparan sulfate proteoglycans of the endothelial cells of the skin blood vessels.

The heparin-binding domains in the spirochete protein, BBK32 are easy to spot in the amino acid sequence of this protein that I downloaded from the NCBI protein database:

>gi|19072701|gb|AAL84596.1| BBK32 [Borrelia burgdorferi]
MKKVKSKYLALGLLFGFISCDLFIRYEMKEESPGLFDKGNSILET
SEESIKKPMNKKGKKIARKKGKSKVSRKEPYIHSLKRDSANKSN
FLQKNVILEEESLKTELLKEQSETRKEKIQKQQDEYKGMTQGSL
NSLSGESGELKETIESNEIDITIDSDLRPKSSLQDIAGSNSISYTDE
IEEEDYARYYLDEDDEDDEYYEDDYEEIRLSNRYQSYLEGVKYNV
DSAINTINKIYDTYTLFSTKLTQMYSTRLDNLAKAKAKEEAAKFTK
EDLEKNFKTLLNYIQVSVKTAANFVYINDTHAKRKLENIEAEIKTL
IAKIKEQSNLYEAYKAIVTSILLMRDSLKEVQGIIDKNGVWY
Basic amino acids are K=lysine, R=arginine

The minimal heparin binding pairs, e.g. KKVKSK are shown in red and the strong heparin-binding triplets, e.g. KRK, are shown in blue. Notice that one triplet is augmented with several pairs to further enhance heparin binding.

I would also expect that BBK32 would be internalized into host cells and transported into the nucleus, where it may alter transcription, a la HIV-TAT. The existence of multiple, strong heparin-binding domains may also serve to bind the BBK32 (or the spirochetes) to multiple different heparan sulfate proteoglycans and interfere with the HSPG circulation system. This may have a toxic effect.

reference:
Norman MU, Moriarty TJ, Dresser AR, Millen B, Kubes P, Chaconas G. Molecular mechanisms involved in vascular interactions of the Lyme disease pathogen in a living host. PLoS Pathog. 2008 Oct 3;4(10):e1000169.