Stress Made Me Solid and Less Human

When we are under acute or chronic episodes of physical or emotional stress, our body protects itself by shifting the relative balance of our nervous system, to  sympathetic dominance (self-control), thereby rapidly releasing specific stress hormones such as cortisol, adrenaline aka epinephrine and noradrenaline aka norepinephrine.   The long-term effects of the continual release of these hormones is not good at all and will eventually lead to significant degenerative changes within the body.

The stress hormone norepinephrine affects parts of the brain where attention and responding actions are controlled.   Along with epinephrine, norepinephrine also underlies the so-called fight-or-flight response.  During this stress response, heart rate increases, glucose is triggered to be released from energy stores, and blood flow is increased to skeletal muscle.  At the same time blood and energy is drawn away from the gastrointestinal tract and other internal organs.

1.  Norepinephrine is synthesized from dopamine by utilizing the enzyme dopamine β-hydroxylase.

2.  The gene for dopamine β-hydroxylase has shown some association linkages with the gene that controls the ABO blood types.(1)

3.  Norepinephrine and epinephrine possess a synergistic relationship with AI-3, an autoinducer* and may even substitute itself for the AI-3 auto-inducer, resulting in biofilm growth.

4.  The common denominator between type O blood and dopamine appears to be via the null allele (A null allele is a mutant copy of a gene  that completely lacks that gene’s normal function).  In this case the null allele is the type O blood allele in the human A, B and O blood type system – A, B and AB blood don’t possess it.

A hypothesis  could then be made, based on the above data, that type O blood individuals who are highly stressed (over-activated adrenal glands and sympathetic nervous system dominant) may possess a predisposition to infections or overgrowth of yeasts, bacterias and biofilm in the GI tract, since both epinephrine and norepinephrine are present throughout the gastrointestinal tract, and are involved in the stress response.  This may be especially relevant for those type O individuals who possess the ‘Hunter’ epigenotype.(2)

*Bacteria communicate via signaling molecules called auto-inducers, a type of bacteria pheromone.  These autoinducers can initiate or interfere with Quorum Sensing.  One of the two series of auto-inducer molecules are the Auto-Inducers AI-1, AI-2 and AI-3.

These autoinducers are one of the very few biologically active family of molecules that contain the element boron.  Some evidence indicates that grapefruit juice and its furocoumarins inhibits autoinducer signaling and biofilm formation in bacteria.  The most abundant source of furocoumarins in our diet would be grapefruit juice.  The average levels of furocoumarins were lower in the juice from red grapefruit than the white variety, with the highest level of  this component found in the meat of the grapefruit.

(1) AF Wilson, RC Elston, R M Siervogel, and LD Tran. Linkage of a gene regulating dopamine-beta-hydroxylase activity and the ABO blood group locus. Am J Hum Genet. 1988 January; 42(1): 160-166.

How Bacteria “Talk” An eight minute video explaining, in simple English, how bacteria communicate through Quorum Sensing (QS)

Bonnie Bassler is a Howard Hughes Medical Institute Investigator and professor in the Department of Molecular Biology at Princeton University

Bonnie Bassler responded to viewer questions and comments about “talking” bacteria.

Q: Is it possible that even when you make a drug to keep the bacteria from “talking” that the bacteria will work their way around the drug that’s stopping them from communicating, just like they’ve worked around current antibiotics?
Alexandra, 7th grade, Manchester, New Hampshire

A: Hi Alexandra,

Absolutely. We know that bacteria will evolve mechanisms of resistance to anti-quorum-sensing therapies. The hope is that because anti-quorum-sensing strategies do not kill bacteria, only keep them from communicating, this is a less harsh treatment and a less stringent selection for resistance. Because of that, the hope is that resistance will develop more slowly than it does to traditional antibiotics. Thus anti-quorum-sensing therapies may have a “longer shelf life” than traditional antibiotics. Of course, we won’t know if that is indeed the case until we make the drug and monitor its effectiveness.

Q: Do bacteria use quorum sensing for a variety of purposes, e.g., fish form schools for protection, lions form prides to hunt? Also, do the same types of bacteria from different colonies communicate differently than the same types of bacteria from different colonies, i.e., do genetically related bacteria recognize each other aside from their being the same species?
Paula, Washington, D.C.

A: Dear Paula,

Quorum sensing is used to control hundreds of different group processes. In the cases we understand best, the processes controlled are ineffective when carried out by individual bacteria acting alone but become effective when carried out in synchrony by the group. Virulence is a good example of a quorum-sensing-controlled behavior. A few bacteria can’t make us sick. Even if they release toxins or other harmful agents, we are HUGE compared to them, so each bacterium’s measly few molecules of a toxin can’t harm us. But, if the bacteria wait, count themselves with quorum-sensing molecules, and then all of the bacteria release their toxins simultaneously, they can overcome an enormous host. There are all kinds of examples of quorum-sensing-controlled group behaviors: bioluminescence, virulence, exchange of DNA, biofilm formation, symbiosis….

Bacteria have multiple chemical languages. We think each bacterial species has a molecule that is unique and represents its own species-specific language. Each unique molecule allows a particular species to know and communicate with its relatives (i.e., have a private conversation). We know there is a universal molecule, a sort of bacterial trade language that bacteria use to converse between species (i.e., a Bacterial Esperanto). There is mounting evidence that many additional molecules remain to be discovered, such as species non-specific molecules that say “who” the neighbor is. This field is only about 10 years old. So far we have only managed to identify a few molecules. We know that bacteria interpret a rich and complex chemical world, and we are working hard to define the complexity of the lexicon.

Q: Can you provide some thoughts on individuals with knee or hip implants and the biofilm some unfortunately develop and if there is hope for probiotics in this issue?
[first name not given] Raunaque, LaCrosse, Wisconsin

A: Dear Mr. or Ms. Raunaque,

Biofilms are communities of bacteria attached to surfaces (for example, as described in the NOVA piece, your teeth in the morning). Biofilms are a cause of constant concern for people with medical implants, heart valves, etc., because these medical devices provide a niche for bacteria to adhere to and thus cause infection. We know that quorum sensing is required for biofilm formation: If the bacteria can’t talk, they can’t make these large, interacting, adherent communities. The goal of many researchers’ studies is to find methods to interfere with biofilm formation, and, of course, a key focus of study is on interrupting quorum sensing. One strategy is to make molecules that antagonize the natural quorum-sensing molecules to impede biofilm formation. Another strategy is the one you suggest, to develop probiotic quorum-sensing therapies that enhance the conversation among our commensal bacteria at the expense of the biofilm formers. Both these avenues are currently being explored.

microparticles "microbubbles" used for detection of bacterial biofilm

Certain types of bacteria, such as: Borrelia burgdorferi, Escherichia coli, Candida albicans, Clostridium difficile, Helicobacter pylori, Klebsiella pneumoniae, Legionella pneumophila, Listeria monocytogenes, Pseudomonas aeruginosa, Salmonella typhimurium, Staphylococcus aureus, Staphylococcus epidermidis, and Vibrio cholerae, can join forces to form protective communities called biofilms.  These thin layers of bacteria, which grow on the surfaces of medical implants or directly on tissue in the body, can be difficult to treat because they are more resistant to drugs than the bacteria on their own.  Currently there is no established way to image biofilms in or out of the body.

Pavlos Anastasiadis and colleagues at the University of Hawaii at Manoa have developed a method to watch and measure growing biofilms with ultrasound.  The researchers used contrast agents, microparticles, more accurately, microbubbles, that are normally injected into the body to improve the quality of ultrasound images.  They modified the surface of bubbles in the agents to stick to two kinds of infectious bacteria that form biofilms (Staphylococcus aureus and Pseudomonas aeruginosa).   Acoustic pulses of ultrasound cause the bubbles to “ring” like a bell, revealing their location and the attached biofilm.

The research was done on isolated biofilms.  The next step will be to test it in living tissue.  Anastasiadis hopes to develop the technique to diagnose infective endocarditis, a disease in which bacterial biofilms form on the inner walls of damaged heart valves.

“Targeted ultrasound contrast agents for the imaging of biofilm infections” by Pavlos Anastasiadis  – Abstract: http://asa.aip.org/web2/asa/abstracts/search.may09/asa323.html

The discovery that bacteria are able to communicate with each other changed our general perception of many single, simple organisms inhabiting our world. Instead of language, bacteria use signaling molecules which are released into the environment. As well as releasing the signaling molecules, bacteria are also able to measure the number (concentration) of the molecules within a population. Nowadays we use the term ‘Quorum Sensing’ (QS) to describe the phenomenon whereby the accumulation of signaling molecules enable a single cell to sense the number of bacteria (cell density). In the natural environment, there are many different bacteria living together which use various classes of signaling molecules. As they employ different languages they cannot necessarily talk to all other bacteria. Today, several quorum sensing systems are intensively studied in various organisms such as marine bacteria and several pathogenic bacteria.

Quorum Sensing & Biofilm Formation

Why do bacteria talk to each other?

(QS) enables bacteria to co-ordinate their behavior. As environmental conditions often change rapidly, bacteria need to respond quickly in order to survive. These responses include adaptation to availability of nutrients, defense against other microorganisms (biofilm formation) which may compete for the same nutrients and the avoidance of toxic compounds (biofilm formation) potentially dangerous for the bacteria. It is very important for pathogenic bacteria during infection of a host (e.g. humans, other animals or plants) to co-ordinate their virulence in order to escape the immune response of the host in order to be able to establish a successful infection. The University of Nottingham Quorum Sensing Research Group

From Dr. Ettinger’s Biofilm Protocol for Lyme and Gut Pathogens: Pathogenic bacteria known to reside in biofilms include: Borrelia burgdorferi, Escherichia coli, Candida albicans, Clostridium difficile, Clostridium perfringens, Helicobacter pylori, Klebsiella pneumoniae, Legionella pneumophila, Listeria monocytogenes, Pseudomonas aeruginosa, Salmonella typhimurium, Staphylococcus aureus, Staphylococcus epidermidis, and Vibrio cholerae. The number of human diseases shown to be associated with biofilms is expanding and includes chronic bacterial prostatitis, chronic rhinosinusitis, cystic fibrosis pneumonia, infective endocarditis, periodontitis, recurrent otitis media, and virtually all device and implant related infections. Strong evidence is also beginning to emerge for an etiologic role of pathogenic mucosal biofilms in gastrointestinal diseases, such as Irritable Bowel Disorders: Crohn’s disease and ulcerative colitis.

Biofilm Formation

What is a biofilm?

Most of you have never heard of the term “biofilm”, but you have certainly encountered “biofilm” on a routine basis. If you’ve ever been to the dentist and he’s scraped “plaque”, which causes tooth decay, off your teeth; that’s a type of bacterial biofilm. The “slim” that clogs your drains is also biofilm. The slippery coating on rocks, at the water’s edge of a stream or river, is just a  bacterial biofilm-coating. Pond-scum – a biofilm. If you’ve ever been diagnosed with Candida albicans, H. pylori or Lyme disease, chances are they’re living, hiding and replicating in a biofilm colony.

Iodine staining of biofilm plaque (upper right)

This is the best product for removing the bacterial biofilm that causes plaque – Biotene PBF Chewing Gum.

These microorganisms (biofilm colonies) are usually encased in an extracellular polysaccharide that they themselves synthesize, via the release of signaling molecules through quorum sensing (QS). This glue-like substance allows them to anchor to all kinds of surfaces – such as metals, plastics, soil particles, medical implant materials, and tissue. As long as sufficient moisture and nutrients are available, a bacterial biofilm can form just about anywhere. In your body that would be from your mouth, especially the teeth, through the stomach and GI tract, all the way down to the rectum. Biofilm in the environment can be found, most often, in ponds, streams, rivers, etc.  A biofilm can be formed by a single bacterial species, but more often than not, biofilms consist of many species of bacteria, as well as fungi/yeast, algae, protozoa, debris and corrosion products. Once anchored to a surface, biofilm microorganisms carry out a variety of detrimental or beneficial reactions, depending on the surrounding environmental or body conditions.

In the human body, biofilm colonies are the main reason that certain conditions take so long to get handled. In my opinion, if it were not for “biofilm”, conditions caused by the microorganisms – Candida albicans, Candida spp,  H. pylori, Lyme’s bacteria (Borrelia burgdorferi) and many others, would be far easier to diagnose and/or treat. It is crucial in any treatment protocol to first handle the biofilm.  By doing so, it will make a significant difference in the amount of time, money and effort spent on treating many, so called, stubborn condition – like the above.

Related Posts: Biofilm Protocol, Quorum Sensing, Lactonase

Biofilm Research and Links/Resources

THE ROLE OF EXTRACELLULAR DNA IN MAINTENANCE OF BIOFILMS FORMED BY E. COLI, H. INFLUENZAE, K. PNEUMONIAE, P. AERUGINOSA, S. AUREUS, S. PYOGENES AND A. BAUMANNII George V. Tetz & Victor V. Tetz Dept. of Microbiology, Virology and Immunology; Saint-Petersburg State Pavlov Medical University, Russia Email: vtetzv@yahoo.com

It is known that bacteria within biofilms are much less susceptible to antibiotics particularly because of poor antimicrobial penetration through surface film that covers microbial community and inactivating role of extracellular matrix. Combined effects of DNase (Enzyme for digesting single and double-stranded DNA) and antibiotics on established biofilms of different unrelated bacteria were displayed. A Combination of antibiotics with DNase I resulted in significant decrease of established biofilm biomass compared to the reduction of biomass achieved when antibiotics or DNase I were used alone.

DETECTION OF HELICOBACTER PYLORI IN BIOFILMS BY USING REAL-TIME POLYMERASE CHAIN REACTION (PCR) Linke, S., Gebel, J., Büttgen, S., Exner, M. Institute for Hygiene and Public Health, University of Bonn

Our results confirmed a possible existence of H. pylori in drinking-water biofilms.

ANALYSIS AND IDENTIFICATION OF THE BIOFILM WOUND MICROFLORA IN HORSE WOUNDS Samantha J. Westgate1, Steven L Percival2*, Derek C. Knottenbelt1 and Christine A. Cochrane1 1University of Liverpool, Department of Veterinary Clinical Science, Division of Equine Studies, Leahurst, Neston, South Wirral, UK *2ConvaTec Wound Therapeutics, Deeside, Flintshire CH5 2NU, UK

Equine wound healing is notoriously problematic on the lower limb, specifically when biofilms are evident. Equine chronic wounds display similar characteristics to chronic wounds in humans thus these cases provide an effective model for human cases. Whether wounds are caused by trauma or surgery their high prevalence is of concern and treatment can be both challenging and costly. Biofilms are considered detrimental to normal healing in non-healing and infected chronic wounds because of their recalcitrant nature towards antimicrobial agents. Biofilms are also known to be resistant to the effects of the immune system. Because of this fact more research in the area of chronic wounds and biofilms is warranted.

Culturable analysis of the microflora revealed that the majority of bacteria isolated from the chronic wounds of horses were Staphylococcus spp, Pseudomonas spp, Micrococcus spp, Enterococcus spp, Corynebacterium spp, Streptococcus spp, Bacillus spp, Aerococcus spp and Clostridium spp. Further analysis of all isolates highlighted their biofilm forming potential and antibiotic resistance profiles. Biofilms were shown to be evident in a large percentage of the chronic wounds. In conclusion these studies provide evidence that biofilms exist in the chronic wounds of horse which may well provide an underlying reason as to why a large percentage of chronic wounds are recalcitrant to antimicrobial therapies, do not heal a timely manner and often become infected.

BACTERIAL BIOFILMS IN SURGICAL SPECIMENS OF PATIENTS WITH CHRONIC RHINOSINUSITIS (sinusitis).
Sanclement JA, Webster P, Thomas J, Ramadan HH. Department of Otolaryngology, West Virginia University, Morgantown, West Virginia 26506-9200, USA.

CONCLUSIONS: Biofilms were demonstrated to be present in 80% the 30 patients undergoing surgery for chronic rhinosinusitis (CRS); none of the (control) patients without CRS had any evidence of biofilms.

First a little background on biofilms:

Fig. 1: The biofilm life cycle. 1: individual cells populate the surface. 2: extracellular polymeric substance (EPS) is produced and attachment becomes irreversible. 3 & 4: biofilm architecture develops and matures. 5: single cells are released from the biofilm. Related Post – Biofilm Basics and Quorum Sensing and Biofilm

This is an excerpt from a Klaire Labs product monograph which is a basic primer on the topic (My additions are in RED) The National Institutes of Health estimates that 60% of all human infections and 80% of refractory infections (def. unresponsive to medical treatment) are attributable to biofilm colonies.  I have seen this, most commonly, in cases I’ve worked-up, where the pathogen is: Chlamydia pneumoniae, Pseudomonas aeruginosa, Helicobacter pylori, [Lyme disease - Borrelia burgdorferi] and Candida albicans.

The protection conferred upon microorganisms by biofilms allows them to achieve a high level of antibiotic resistance, stealth and invisibility.  Biofilms not only provide a physical barrier to antimicrobial agents (pharmaceutical antibiotics) and host antibodies, but facilitate the exchange of antibiotic-resistant genetic material between organisms and may contain antibiotic-degrading enzymes such as b-lactamase, effectively neutralizing incoming antibiotic molecules.  The decreased growth rate of sessile microorganisms (def. Permanently attached to a substrate; not free to move about; “an attached oyster”) also reduces their antibiotic susceptibility as most antimicrobial agents require rapid cell growth in order to effectively kill or inhibit the microbes.  Biofilms thus render pathogenic microorganisms enormously difficult to eradicate, and can almost single-handedly contribute to localized or systemic inflammatory reactions and delayed wound healing.  Depending on the type of biofilm, one or more species of pathogens may be found embedded in the extracellular polymeric substance (def. Composed primarily of polysaccharides and can either stay attached to the cell’s outer surface, or be secreted into its growth medium).  Bacterial extracellular polymeric substance (EPS) maybe a carrier of, or may have heavy metals embedded in them, thus the indication for chelation w/EDTA).

Pathogenic bacterial known to reside in biofilms include: Borrelia burgdorferi, Escherichia coli, Candida albicans, Clostridium difficile, Clostridium perfringens, Helicobacter pylori, Klebsiella pneumoniae, Legionella pneumophila, Listeria monocytogenes, Pseudomonas aeruginosa, Salmonella typhimurium, Staphylococcus aureus, Staphylococcus epidermidis, and Vibrio cholerae. The number of human diseases shown to be associated with biofilms is expanding and includes chronic bacterial prostatitis, chronic rhinosinusitis, cystic fibrosis pneumonia, infective endocarditis, periodontitis, recurrent otitis media, and virtually all device and implant related infections.  Strong evidence is also beginning to emerge for an etiologic role of pathogenic mucosal biofilms in gastrointestinal diseases, such as Irritable Bowel Disorders: Crohn’s disease and ulcerative colitis.

S. aureus biofilm

Dr. Marcus Ettinger’s Biofilm Protocol – Only the eradication phase is presented here.  There is a pre,  post and toxin reduction step as well.  I will add  these soon.

A. Products (mandatory products in RED):

1. Monolaurin (lauric acid) 600mg’s 2 caps 2x per day
2. Nutiva Extra-Virgin Coconut Oil (almost 50% lauric acid by volume) 1-3 tablespoons per day
3. Nattokinase (a potent fibrinolytic enzyme) 100mg’s  1-3 times per day
4. InterFase Plus™ (broad-spectrum enzyme formula w/EDTA) 2 caps 3x/day on an empty stomach
5. Serrapeptase or (Serrazimes – Now Foods) 20,000 units 2x per day
6. Vitamin C (ascorbic acid – Not buffered, as most of these contain metals) 500mg’s 4x/day

B. Avoid Supplemental forms of: Magnesium, Iron and Calcium as they may feed the biofilm.

C. Take a broad spectrum probiotic and prebiotic.  I like the combination of Now Foods brand Gr8, 2-3 per day and their Probiotic Defense Powder, 1/4 tsp 2-4x per day.  These products will help to crowd out the bad bacteria, and also help disrupt biofilm colonies along the mucus membrane.

D. Specific Additions based on condition:

1. Candida* – SF722 (10-Undecenoic Acid  50 mg) Thorne Research. I’ve used 9 up to 20 a day with clients. This is as close as you can get to a medication and still be natural.  There are a few chat rooms blasting this product, based on who knows what.  I’ve used it for over 15 years and it is amazing, never a problem!  *Do not take if you are allergic to fish.
2. Chlamydia pneumonia – Pneumotrophin PMG by Standard Process, Inc. 1 tab 3x/day. How it works.  I use it because it helps direct the body’s attention to the lung where it is needed most.
3. H. pylori – Complete write-up on another post.
4. Chronic bacterial prostatitis – Quercitin (600mg’s) and Bromelain (200mg’s) combination by Now Foods. 3-6 capsules per day. Decreases inflammation and oxidant stress in the prostate while increasing local concentrations of beta-endorphins.

If you are interested in ordering any of these products, please contact our office/Rene at (714) 639-4360, for product and shipping costs.