“Communities” Survive Better
People realized, long ago, that they could survive better if they gathered into groups. It didn’t take long to realize that having people of different talents was beneficial to all. They realized that a community is more likely to survive if one organizes, another gathers resources, another makes food, and still another protects the community against invaders. Grouping together inside places of shelter is a logical way to enhance survival.
It didn’t take long to see that working together requires communication and cooperation. Mankind, of course, has very developed communication (cooperation is always a challenge). However, other types of life with much less thinking ability have also built communities; wolf packs, prairie dogs, schools of fish, crows, ants and, yes, even bacteria!
So, it should not come as a surprise that scientists are finding diseases we harbor for years have long ago evolved ways to join together into communities. There is a difference between planktonic (acute) infections and biofilm (chronic) infections.
Acute short-term diseases: (a sliver, a cut, diarrhea, etc.) are from pathogens that are generally free-floating planktonic bacteria.
Biofilm chronic diseases: (Lyme disease, MRSA, CFS, etc.) are pathogens that build communities. Why? Because they are better able to defend against our immune system and antibiotics that want to destroy them!
It turns out that a vast number of the pathogens we harbor are grouped into communities called biofilms. JW Costerton, of The Center for Biofilm Engineering, defines a bacterial biofilm as “a structured community” of bacterial cells stuck to forming a protective matrix around themselves.(1)
Biofilm Development and Movement
The biofilm life cycle acts in three steps:
2. Growth of colonies (development)
3. Periodic spreading
The first biofilm bacterial colonists that start can anchor themselves on a surface using cell adhesion molecules. These are proteins on their surfaces that bind other cells in a process called cell adhesion. (The protein aspect is important for biofilm enzymes.) Then they provide different surfaces so other bacteria, unable to attach to a surface on their own, can anchor themselves to the biofilm matrix.
Then, things start to get interesting. Many studies show that, during the time a biofilm is being created, the pathogens inside it can communicate with each other! They do this through something called “quorum sensing”. They emit chemical messages that other bacteria are able to recognize. This is not as sophisticated as humans (neither are ants) but it is still effective.
If a bacteria senses that it is surrounded by other pathogens, it is more inclined to join them and a biofilm starts to form. D.A. Higgins says when the messages grow strong enough, the bacteria respond “en masse” and starts to behave as a group.(2) The cells in a biofilm “talk” to each other, via quorum, enough to build microcolonies that can actually keep water and nutrition channels open!
In fact, in 1999, a research team, involving D.H. Singh, screened the entire bacterial genome, identifying 39 genes that are strongly controlled by this ‘quorum-sensing system’. These are the quorum-sensing molecules that are the signals for biofilm formation.(3)
Once the biofilm attachment colonization has begun, its development allows for the cells inside to become more resistant to antibiotics. The biofilm grows through a combination of:
Cell division of the bacteria within the biofilm, and
Recruitment by chemically attracting.
An interesting study by Cho describes how once a biofilm has officially formed, it often contains channels in which nutrients can circulate. They are sometimes compared to the tissues of higher organisms, in which closely packed cells work together and create a network in which minerals can flow. If you look at naturally occurring biofilms, they have very complicated architecture. They are like cities with channels for nutrients to go in and waste to go out.(4)
Different bacteria in the biofilm use different nutrient resources. An article in Current Biology says the bacteria doesn’t all compete for the same chemicals and nutrients substantially reduces competition for resources within the biofilm. They can also pick and choose those belonging to the biofilm and fewer loafer “cheaters”.(5) The longer the packed bacteria remain, the more ordered the biofilm structure became. As the cells in the biofilm became more ordered and tightly packed, the biofilm became harder and harder to penetrate!
3. The Spread of Biofilms
Biofilm infections are often slow to produce obvious symptoms. However, a study by J. Stoodley describes how biofilm bacteria can move in different ways that allow them to easily infect new tissues. Biofilms may move collectively, by rippling or rolling across the surface, or by detaching in clumps and attaching elsewhere.(6)
Researchers often note that, once biofilms are established, planktonic bacteria may periodically leave the biofilm on their own. When they do, they can rapidly multiply and disperse. When these bacteria are periodically released from the biofilms, the immune system suddenly becomes aware of their presence. It mounts an inflammatory response that may be what causes many chronic relapsing infections.
Chronic illness biofilms don’t often kill a person like acute pathogens do (ex: rabies or flu). P.K. Singh says bacteria actually benefit by keeping the host alive.(7) After all, if a chronic biofilm simply killed its host, it will no longer have a place to live! So, chronic infections often find a balance in a “disease stalemate” where the infectious agents never actually kill the host, but the host is never able to fully kill the invading pathogens either. This is part of the reason they are “chronic”.
In just a short period of time, researchers studying internal biofilms have already pegged them as the cause of many chronic infections and disease. The list of illnesses attributed to these bacterial colonies continues to grow rapidly. It is becoming pretty obvious that research on internal biofilms has been largely neglected, despite the fact that bacterial biofilms seem to have great potential for causing human disease.
Common Sites of Biofilm Infection
Besides the illnesses listed above, there are other conditions owing to biofilms:
Dental Plaque: Perhaps the most well-studied biofilms are those that make up what is commonly referred to as dental plaque. Hundreds of microbial biofilm colonize the human mouth, causing tooth decay and gum disease. Singh adds that plaque is a biofilm on the surface of the teeth that subject the teeth and gingival tissues to high concentrations of bacterial metabolites which result in dental disease.(8)
Chronic Sinusitis: It has also recently been shown that biofilms are present on the removed tissue of 80% of patients undergoing surgery for chronic sinusitis.
Osteomyelitis: Biofilms may also cause osteomyelitis, a disease in which the bones and bone marrow become infected.
Chronic prostatitis: Studies have also documented biofilms on the surface of the prostatic duct.
Toxic Shock Syndrome: Microbes that colonize vaginal tissue and tampon fibers can also form into biofilms, causing inflammation and disease such as Toxic Shock Syndrome.
Kidney Stones: Biofilms also cause the formation of kidney stones. The stones cause disease by obstructing urine flow and by producing inflammation and recurrent infection that can lead to kidney failure.
Endocarditis: Then there’s endocarditis, a disease that involves inflammation of the inner layers of the heart. The primary infectious lesion in endocarditis is a complex biofilm composed of both bacterial and host components that is located on a cardiac valve.
Medical Devices: A study in the New England Journal of Medicine finds a variety of pathogenic biofilms are also commonly found on medical devices such as joint prostheses and heart valves. Individuals with prosthetic joints are often oblivious to the fact that their prosthetic joints harbor biofilm infections.(9)
Cystic Fibrosis: Infection by the bacterium Pseudomonas aeruginosa (P. aeruginosa) is the main cause of death among patients with cystic fibrosis. Pseudomonas is able to set up permanent residence in the lungs of patients with cystic fibrosis where, if you ask most mainstream researchers, it is impossible to kill. Eventually, chronic inflammation produced by the immune system in response to Pseudomonas destroys the lung and causes respiratory failure, a study in Microbiology reports.(10)
Ear Infections (OM): It wasn’t until 2006 that researchers realized that 92% of ear infections are caused by biofilm bacteria. These infections, which can be either acute or chronic, are referred to collectively as otitis media (OM). They are the most common illness for which children visit a physician, receive antibiotics, or undergo surgery in the United States. It appears that recurrent disease stems not from re-infection as was previously thought but from a persistent biofilm as reported by Hall-Stoodley et. al.(11)
Diabetic Wounds: Dr. Randall Wolcott who just recently discovered and confirmed that the sludge covering diabetic wounds is largely made up of biofilms. Such limbs generally had to be amputated. Now that they have been correctly linked to biofilms, measures can be taken to stop the spread of infection and save the limb.(12)
Chronic Inflammatory and Biofilm Bacteria
Chronic inflammatory diseases result from infection with a large microbiota of chronic biofilm and L-form bacteria (collectively called the Th1 pathogens) as reported by James, Marshall et al.(12-13) Most of the pathogens that cause inflammatory disease have one thing in common – they have all developed ways to evade the immune system. They persist as chronic forms that the body is unable to eliminate naturally.
Some L-form bacteria evolved the ability to reside inside macrophages, the very white blood cells of the immune system that are supposed to kill invading pathogens. L-form bacteria also lose their cell walls. This makes them impervious to the immune response that detects invading pathogens by identifying the proteins on their cell walls. As noted in Clinical Microbiology Reviews, this also means that the beta-lactam antibiotics, which work by targeting the bacterial cell wall, are completely ineffective at killing them.(14)
Once enough chronic pathogens have grouped together and formed a stable community with a strong protective matrix, they are likely able to reside in any area of the body, causing the host to suffer from chronic symptoms that are both mental and physical in nature. T.G. Marshall found Th1 pathogens are capable of inactivating the Vitamin D Receptor that controls the body’s first line of defense against intracellular infection.(15) Thus, as patients accumulate a greater number of the Th1 pathogens, it causes a snowball effect, in which the patient becomes increasingly immune compromised.
Anyone who is skeptical about the fact that biofilms likely form a large percentage of the microbiota which cause inflammatory disease should consider studies that have found a link between periodontal disease and several major inflammatory conditions. The British Medical Journal showed a correlation between dental disease and systemic disease (stroke, heart disease, diabetes).
Researchers from the Canadian Health Bureau found that people with periodontal disease had a two times higher risk of dying from cardiovascular disease.(16) If inflammatory pain and issues are a problem, a person can add our Inflammation Relief formula to our Lyme protocol.
The medical community is rapidly acknowledging the large number of diseases and infections caused by biofilms. However, most researchers are convinced that biofilms are difficult or impossible to destroy – particularly those cells that form the deeper layers of a thick biofilm. Most papers on biofilms state that they are resistant to antibiotics administered in a standard manner. Other teams have also come up short in creating methods to break up the biofilms.
This means patients with biofilm infections are generally told by mainstream doctors that they have an untreatable infection. In some cases, a disease-causing biofilm can be cut out of a patient’s tissues, or efforts are made to drain components of the biofilm out of the body.
1. The Wrong Way
Mainstream researchers have repeatedly tried to kill biofilms by giving patients high, constant doses of antibiotics. Unfortunately, when administered in high doses, the antibiotic may temporarily weaken the biofilm but is incapable of destroying it, as a number of cells called “persisters” are left behind and allow the biofilm to regenerate. In a few months, it reappears, and it is usually in an antibiotic-resistant form.
2. A Better Way: Pulsed Dosing
T. Marshall was the first to create an antibiotic regimen that has better possibly to destroy biofilms. Central to the treatment, called the Marshall Protocol, is the fact that biofilms and other Th1 pathogens succumb to specific bacteriostatic antibiotics taken in very low, pulsed doses. It is only when antibiotics are administered in this manner that they have a possibility of eradicating biofilms.(13,15)
Cogan and Cortez, in the Bulletin of Mathematical Biology, found that during low pulsed dosing, where an antibiotic is administered, withdrawn, and then administered again, the persister cells are unable to switch back into biofilm mode. A second application of the antibiotic should then completely eliminate the persister cells, which are still in planktonic mode.(17)
Pulsed dosing depends on the rate at which persisters lose resistance and regenerate new persisters. It also depends on the ability to manipulate the antibiotic concentration. The Marshall Protocol uses a total of five bacteriostatic antibiotics, usually taken two or three at a time.
The danger, of course, is that bacteria that live through antibiotic dosing can go on to produce resistant strains. It also has to be taken in conjunction with a medication called Benicar, which activates the Vitamin D Receptor of the immune system.
3. The Best Way: Our 3-Step Protocol
This is a complete, natural program:
1. Monolaurin to kill the bacteria
2. Biofilm Enzymes to dissolve the biofilm and cysts
3. Heavy Metal Detox to eliminate the heavy metal and toxins
(And ongoing ‘Maintenance’ prevention.)
Link to a sample 3-Step Protocol with Lyme disease. (Other disease protocols may vary a bit.)
1. Costerton, J. W., Stewart, P. S., & Greenberg, E. P. (1999). Bacterial biofilms: a common cause of persistent infections. Science (New York, N.Y.), 284(5418), 1318-22.
2. Higgins, D. A., Pomianek, M. E., Kraml, C. M., Taylor, R. K., Semmelhack, M. F., & Bassler, B. L. (2007). The major Vibrio cholerae autoinducer and its role in virulence factor production. Nature, 450(7171), 883-6.
3. Singh, P. K., Schaefer, A. L., Parsek, M. R., Moninger, T. O., Welsh, M. J., & Greenberg, E. P. (2000). Quorum-sensing signals indicate that cystic fibrosis lungs are infected with bacterial biofilms. Nature, 407(6805), 762-4.
4. Cho, H., Jönsson, H., Campbell, K., Melke, P., Williams, J. W., Jedynak, B., et al. (2007). Self-Organization in High-Density Bacterial Colonies: Efficient Crowd Control. PLoS Biology, 5(11), e302 EP -.
5. Brockhurst, M. A., Hochberg, M. E., Bell, T., & Buckling, A. (2006). Character displacement promotes cooperation in bacterial biofilms. Current biology: CB, 16(20), 2030-4.
6. Stoodley, P., Purevdorj-Gage, B., & Costerton, J. W. (2005). Clinical significance of seeding dispersal in biofilms: a response. Microbiology, 151(11), 3453.
7. Parsek, M. R., & Singh, P. K. (2003). Bacterial biofilms: an emerging link to disease pathogenesis. Annual review of microbiology, 57, 677-701.
8. Parsek, M. R., & Singh, P. K. (2003). Bacterial biofilms: an emerging link to disease pathogenesis. Annual review of microbiology, 57, 677-701.
9. Trampuz, A., Piper, K. E., Jacobson, M. J., Hanssen, A. D., Unni, K. K., Osmon, D. R., et al. (2007). Sonication of Removed Hip and Knee Prostheses for Diagnosis of Infection. N Engl J Med, 357(7), 654-663.
10. Ristow, P., Bourhy, P., Kerneis, S., Schmitt, C., Prevost, M., Lilenbaum, W., et al. (2008). Biofilm formation by saprophytic and pathogenic leptospires. Microbiology, 154(5), 1309-1317.
11. Hall-Stoodley, L., Hu, F. Z., Gieseke, A., Nistico, L., Nguyen, D., Hayes, J., et al. (2006). Direct Detection of Bacterial Biofilms on the Middle-Ear Mucosa of Children With Chronic Otitis Media. JAMA, 296(2), 202-211. [↩]
12. James, G. A., Swogger, E., Wolcott, R., Pulcini, E. D., Secor, P., Sestrich, J., et al. (2008). Biofilms in Chronic Wounds. Wound Repair and Regeneration, 16(1), 37-44.
13. Marshall, T. G., & Marshall, F. E. (2004). Sarcoidosis succumbs to antibiotics–implications for autoimmune disease. Autoimmunity reviews, 3(4), 295-300.
14. Sr, G. J. D., & Woody, H. B. (1997). Bacterial persistence and expression of disease. Clinical Microbiology Reviews, 10(2).
15. Marshall, T. G. (2007). Bacterial Capnine Blocks Transcription of Human Antimicrobial Peptides. Nature Precedings.
16. Morrison, H. I., Ellison, L. F., & Taylor, G. W. (1999). Periodontal disease and risk of fatal coronary heart and cerebrovascular diseases. Journal of cardiovascular risk, 6(1), 7-11.
17. Cogan, N. G., Cortez, R., & Fauci, L. (2005). Modeling physiological resistance in bacterial biofilms. Bulletin of mathematical biology, 67(4), 831-53.
Falkinham Iii, J. O., Iseman, M. D., Haas, P. D., & Soolingen, D. V. (2008). Mycobacterium avium in a shower linked to pulmonary disease. Journal of water and health, 6(2), 209-13.
Fusarium and Candida albicans Biofilms on Soft Contact Lenses: Model Development, Influence of Lens Type, and Susceptibility to Lens Care Solutions. Antimicrob. Agents Chemother., 52(1), 171-182.
Imamura, Y., Chandra, J., Mukherjee, P. K., Lattif, A. A., Szczotka-Flynn, L. B., Pearlman, E., et al. (2008).
Lewis, K. (2001). Riddle of biofilm resistance. Antimicrobial agents and chemotherapy, 45(4), 999-1007.
Marshall, T. G. (2006b). A New Approach to Treating Intraphagocytic CWD Bacterial Pathogens in Sarcoidosis, CFS, Lyme and other Inflammatory Diseases.
Marshall, T. G. (2006). VDR Nuclear Receptor Competence is the Key to Recovery from Chronic Inflammatory and Autoimmune
Starner, Timothy D et al. 2008. Subinhibitory Concentrations of Azithromycin Decrease Nontypeable Haemophilus influenzae Biofilm Formation and Diminish Established Biofilms. Antimicrobial agents and chemotherapy 52(1):137-45.
Stewart, R., & Hirani, V. (2007). Dental Health and Cognitive Impairment in an English National Survey Population. Journal of the American Geriatrics Society, 55(9), 1410-1414.