Research into Candida biofilms is relatively new so our understanding of them is still limited and in progress, but this appears to be one of the reasons why so many people are not able to eradicate their yeast overgrowth. They are one of the most frightening, but fascinating aspects of this organism, and microbes in general.
A biofilm is a complex, dynamic, three-dimensional, slimy, sticky, film or glue-like, polysaccharide (think sugar, starch, inulin, cellulose) and protein structure (referred to as extracellular matrix) that Candida (and other microbes) create so that it can hide out from your immune system, antifungals or anything else that is a threat to its existence. The biofilm becomes a “protective shield” so to speak. Instead of free-floating around your body independently as a single cell, a large population of yeast organisms attach themselves to the surface of the biofilm (colonization) and create their own ecosystem.
Biofilms also exist within industrial settings, which is where we have learned much of what we know about them, as they are easier to observe here. You encounter them in your daily life in a variety of ways. Dental plaque, the slimy gunk that clogs your drain and that develops on rocks in a stream are all biofilms. They exist in the kitchen and the bath in sinks, toilets, cutting boards, and countertops.
In the United States, billions of dollars are lost each year to biofilms due to damage to equipment, contamination of products and medical infections. However, on the other hand they can also be beneficial at places like hazardous waste sites, wastewater treatment, and preventing contamination of soil and groundwater. Water that is used for drinking is more stable biologically and has a lower demand for disinfection if it has been subjected to microbes prior to treatment. In nature they are a food source for other organisms. So like all living things they serve a purpose in the ecosystem.
Biofilm formation is one of the many ingenious ways that microbes have developed to survive. They may accumulate on almost any surface that provides them a mixture of moisture and the right nutrients, including natural materials, metals, plastics, above-ground or underground, and body tissue. Biofilm are a combination of liquid and solid, but in an industrial setting, they can become more solid and brittle when they collect sediment, rust or calcium deposits.
The human body is seen as just another surface for them to colonize. They may exist within or outside the body, and are found in places like the blood, the gut, mouth, teeth, sinuses, adenoids and on medical devices implanted in the body. Once cells attach to a particular surface, there is cell division, proliferation and development of biofilm.
Free-floating plankton (yeast cells in this case) approach a surface and become attached where they begin to produce the glue-like substance and colonize the surface. The matrix substance enables them to form a complex three-dimensional structure, and the biofilm community can develop within hours. Biofilms detach as clumps or release new cells to grow and disperse into other areas.
A mature Candida biofilm displays a spaciously distributed and complex three-dimensional architecture, that is optimized to enable them to receive nutrients, get rid of waste products and establish micro niches throughout the matrix and houses a thick web of yeasts, hyphae, and pseudohyphae. The matrix may range in thickness of 25 to more than 450 µm. The tissue in the areas where the biofilm adheres is damaged and inflammation occurs. In an industrial setting (like water distribution) a thick biofilm can reduce the flow of water, so we can assume that the same could happen in the bowel.
When Candida (and other microbes) are in a group like this, then it behaves and responds to treatment very differently than it does outside the group. Treatment approaches that are typically effective against single cells may not work at all against a large organized community. Like any community, there is strength in numbers. Your immune system and antifungals cannot reach the yeast that is within the biofilm to eliminate it.
Normally the immune system recognizes an invader by the proteins in its outer membrane. When the microbes are in the biofilm it works as a “cloaking device” preventing the immune system from detecting the proteins in the membrane and thus it doesn’t launch an attack and the microbes are free to proliferate.
So for example, when single-cell organisms are inhaled by an individual, phagocytes (part of the immune system) in the alveoli of the lungs will gobble them up and they will not cause infection in the lungs. However, if a fragment of a biofilm is inhaled, (like might be found in a hospital setting or a sick building), the phagocytes cannot reach them and infection develops. Biofilms were implicated in the outbreak of Legionnaires’ disease that were disseminated through the air conditioning and ventilation systems of hotels.
Candida organisms (and all other types of microbes) within a biofilm are dramatically more resistant to antifungal agents (or whatever agent is required to eliminate the particular type of organism). A biofilm community may be as much as 1000 times more resistant than free-floating organisms. However, their actual mechanisms to achieve this resistance are not completely clear.
Research suggests that the more mature the biofilm, the more resistance develops. The longer you have had Candida, the more time it has had to develop strong biofilms. In one study, they illustrated that Candida cells outside the matrix were not resistant to a particular antifungal, but the longer the matrix developed the more resistant they became.
It appears the resistance is the result of many multi-faceted and complex mechanisms that are not yet fully understood. Speculation suggests it may include the high density of cells within the biofilm; the effects of the biofilm matrix; decreased growth rate and nutrient limitation; the expression of resistance genes; and the presence of “persister” cells.
Although biofilms may develop with many species of yeast, Candida Albicans species is the yeast that is most commonly associated with biofilms and Candida parapsilosis is second most common in a hospital setting. However, it’s interesting to note that C. parapsilosis biofilms contain less matrix material and are less complex than C albicans biofilms, but they have just as much as resistance. This clearly illustrates that there other factors in the biofilm that we have yet to understand. The capacity to create biofilms fluctuates within various strains of Candida Albicans and other species.
Candida’s ability to morph into different forms (from yeast to hyphae) seems to play a significant role in some biofilm structures, but not all. In some studies, the hyphae were necessary components of the integrity and multi-layered design of a mature biofilm. However, some biofilms do consist of yeast cells only, with no hyphae. It is believed that the hyphae are needed for the more sophisticated structures.
Most of the studies done on biofilms have been in situations where there is a prosthetic heart valve, a hip replacement, intravenous catheters, or other implanted medical device, but we can assume that what we observe in this situations about biofilms can be applied more broadly. However, do note, that if you have any of these devices, that colonization and biofilm formation on and around these devices is quite common and can cause very significant issues. This also includes breast implants, teeth implants, pacemakers, IUDs, contact lenses, shunts, stents, endotracheal tubes, artificial joints, metal bars or anything foreign that is inserted in the body. They may be a never-ending source of infection and even lead to malfunction of the apparatus. Removal of the device may be necessary. Candida cells can also bind to bacteria.
A biofilm is responsive to its environment and can migrate across surfaces. Organisms within the biofilm can detach from the matrix and travel individually or in a clump. If they detach as a clump, they retain their increased resistance against antifungals, antibacterials, etc.
Genetic Expression is Altered in the Biofilm
All living organisms (including those within a biofilm) have DNA molecules composed of genes that transport the instructions that determine the characteristics and cellular activities of that organism, as well as what genetic material will be transferred to other generations through reproduction. So for example, the genes of a microbe will determine how it acquires nutrients, gets rid of waste, responds to its environment and what characteristics it will pass on to its offspring. These instructions are what keeps the organism alive. It has been found that microbes within a biofilm are expressing a different set of gene instructions (gene expression) than planktonic (free-floating) organisms are expressing, thus engaging in different activities and responding differently to their environment.
The individual yeast cells have the ability to communicate with one another and with other species using chemical signals, and this communication has been found to be vital in the formation of the biofilm. In studies where chemicals were used to inhibit cell-to-cell communication, formation of the biofilm was inhibited. These chemical signals have been shown to impact not only the structure of the biofilm, but attachment, detachment and other behaviors.
In their planktonic state, the chemical signals are not strong enough to modify gene expression, but the matrix material of the biofilm keeps them in such close proximity that it allows the chemical signals to build up, which enables them to alter genetic activity, and consequently, cellular behavior. They will turn on or turn off particular genes as needed to benefit the population. Some genes will not be activated until they sense through their chemical communications whether the population is large enough. The ability to recognize the population is called Quorum Sensing.
Evidence also suggests that the cell-to-cell signaling communication system allows them to create sub-populations where each one carries out a different activity needed to support the group. For example, one sub-population may work on acquiring nutrients, while another sub-population focuses on reproduction. Some cells may even be sacrificed for the better good of the group when implementing some of their strategies. Some microbes are able to share information with one another like a drug-resistant gene.
The changes in genetic expression that occur within the biofilm are what enables the organisms to hide so effectively from the immune system and become more resistant to antifungals, antibacterials or whatever the case may be. It is hypothesized that they acquire these abilities in the following ways: yeast and other microbes in the planktonic state carry a lot of genetic code that cannot really be expressed until they become a group; because they are so vulnerable to antifungal or antibacterial agents as a planktonic they die before it can be activated. Additionally, they may be able to neutralize an antifungal or antimicrobial more efficiently as a group than they can as a single cell and persister cells that are spawned in the planktonic state are more vulnerable than persister cells spawned in the matrix.
A persister is a hypothetical cell state or variant of a regular cell for fungi or bacteria that doesn’t grow or die in the presence of agents that should kill them, (dormant) exhibiting multi-drug tolerance. They consist of only about one percent of the entire population, but this is enough to repopulate the colony, should the rest of the population get decimated.
Some other coordinated behaviors within sub-populations that have been observed are “swarming or swimming” and wall forming. The wall formers, being those that form the wall of the fortress while the swarmers create daughter cells.
So in a nutshell, the single yeast cells (or other microbes) are able to form together and use coordinated behavior and division of labor to enhance their survival abilities, just like we humans do in our own communities.
The Candida Biofilm Houses Many Different Microbes
Although a biofilm may consist of only one species, they almost always consist of a mixture of microbes including many different species of Candida, fungi, bacteria, protozoa, and parasites. For example, more than 500 different species of bacteria have been found in dental plaque biofilms.
The structure of the biofilm consists of gradients and niches that offer living conditions that are suited to a wide variety of microbes. For example, one niche or gradient within the matrix may be rich in oxygen, while another may be void of oxygen. Therefore aerobic microbes would dominate the oxygen-enriched areas of the biofilm, while anaerobic microbes will dominate the oxygen-depleted areas of the biofilm. Some microbes feed on the waste products of other microbes. If a microbe is in area where it is difficult for nutrients to reach, they may become slow-growing or stop growing, which makes them less susceptible to agents that may kill them.
Therefore, a Candida biofilm may house a variety of other species or organisms and vice versa, so understanding the characteristics, behaviors, etc., of each organism and their biofilm may be necessary since each organism may be contributing to how the biofilm is impacting the body. We need to understand how their interaction with one another affects the biofilm.
Hundreds of different microbes have been found to be coexisting within a biofilm together. For example, the biofilm may contain Candida Albicans, Candida parapsilosis, Candida tropicalis and many different strains of each of those, plus it may also house numerous bacteria as well as a variety of parasites.
Candida Biofilm Treatment
Just like the yeast cells themselves, the biofilm is extremely hardy and difficult to destroy. It is a slow process that takes a great deal of time and persistence; possibly years. The process is still experimental and has not been refined. Researchers are still trying to determine which products are the most effective and what we have so far doesn’t work exactly as they are needed. Some people are improving greatly with these techniques, some mildly and some not at all.
Research has universally demonstrated that bacteria that are part of a biofilm community are much less susceptible to antimicrobials than the same bacteria outside the biofilm. Research at the Center for Biofilm Engineering have found that microbial biofilms in an industrial setting are treated most effectively with a higher concentrated dose of an antimicrobial. A short exposure to a concentrated dose has been found to be more effective than a low exposure to a lower dose. However, they note that in a medical setting, the dose of antimicrobial needed to destroy the biofilm may also kill the patient.
Biofilms from Candida Albicans and Candida Tropicalis have been found to consist of carbohydrate, protein, hexosamine, phosphorous and uronic acid. However, C. Albicans consisted mostly of glucose (32 percent), while C. Tropicalis consisted mostly of hexosamine (27 percent). The material of the matrix was found to affect how it responded to antifungals; some being more resistant than others. So this can help us understand why one antifungal is effective against one species and not another.
What this also illustrates is that sugar and carbohydrates do not only feed the yeast organisms itself, but they will also provide the materials needed to strengthen the biofilm. So the Candida diet is also an important component of weakening the matrix, not just restricting food for the organism itself.
Most biofilms of microbes in general also consist of minerals like calcium, iron and magnesium, DNA and fibrin (a protein created by our body for clotting the blood). It is believed the iron, calcium and magnesium help hold the matrix together and iron plays a vital role in their ability to evade the immune system. Thus supplementing with these minerals when trying to destroy a biofilm may inadvertently reinforce the matrix.
When iron is present, the outer protein membrane of the invader is not expressed. Normally, our body produces lactoferrin and transferrin to mop up excess iron and prevent biofilm development, but the pathogenic microbes are able to secrete iron chelators that compete with lactoferrin and transferrin and acquire the iron they need for survival.
Lyme bacterium (Borrelia burgdorferi) uses manganese instead of iron for its survival, which enables it to get around this whole process and evade the immune system.
An agent is needed that can break down the unique characteristics of the matrix that may be somewhat different from species to species and strain to strain. There are a variety of different drugs and natural remedies that a practitioner may recommend. What works for one person may not work for another.
Liposomal formulations of Amphotericin B and a class of antifungals called echinocandins have been found to more effective against some Candida biofilms than other antifungals, but not all. As a matter of fact, in some studies the species and strains were resistant to everything but echinocandins and liposomal Amphotericin B, but this could simply be because these drugs have been around a shorter amount of time. However, some studies have found that Candida within a biofilm can become completely resistant to all antifungal agents.
Echinocandins are a class of antifungals that inhibit the synthesis of glucan (carbohydrate or polysaccharide) in the cell wall of the biofilm, which is a basic substance within the cell wall of the yeast organism itself as well. Amphotericin and echinocandins have shown that they can also reduce the ability of yeast planktonic cells (basic yeast cells) to form into a biofilm.
Some other substances that have been found to be effective against biofilms include clove, lemongrass, serrapeptase, nattokinase, lumbrokinase, and a variety of other enzymes, as well as n-acetyl-cysteine, cis-2-decenoic acid (a fatty acid messenger, tindamax, and apple cider vinegar.
One study found that NAC reduced biofilm formation by 62 percent for a variety of different bacteria, including Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Klebseilla pneumoniae, Pseudomonas aeruginosa and Proteus vulgaris. Candida was not included in this test, but it is assumed it should have a significant impact since all biofilms share similar characteristics. However, why it works is not really known. NAC is an antioxidant that helps the body produce more glutathione and supports parts of the immune system that regulate mucosal surfaces, but how it is penetrating the biofilm is not understood.
These products contain a variety of natural substances that are believed to degrade or break down the polysaccharides, fibrin and other materials that form the architecture of the biofilm and bring the fortress crumbling down, thus making it easier for the immune system and antifungals to kill the yeast. They should be used in conjunction with antifungals or antimicrobials or antiparisitics.
Antifungals (or antibiotics or antiparisitics medicines as well) cannot penetrate the biofilm to kill the microbe, so the biofilm must be destroyed first. When that is achieved, this allows the immune system and the agent to work in conjunction. An antifungal or antimicrobial agent can only work with your immune system, it just tips the scale in your favor so the immune system can get the upper hand. Thus, if the biofilm is destroyed, we can increase our success in eradicating overgrowth of yeast, bacteria and parasites.
For example, MRSA/VRSA became resistant to vancomycin, but they discovered if they treated with EDTA first, this pulled out the calcium, magnesium and iron and destroyed the biofilm. Then the vancomycin was effective against MRSA. Suggesting that the Candida biofilm may be attacked in the same way. Use one agent to break down the walls of the matrix and then an antifungal agent to get the yeast as they are released. The chelator is used to get rid of the minerals the matrix is using.
As I mentioned previously, many pathogens besides Candida have developed the ability to create biofilms. They are common in all bacteria like Lyme and parasites as well; both of which commonly occur in conjunction with Candida. So an individual may essentially have biofilms for Candida, bacteria, and parasites, and the matrix for each of these organisms may consist of a variety of different materials, which means what gets rid of one, does not necessarily get rid of the other. Each issue may need to be addressed independently. Remember some organisms of one species may hide out in another species matrix and vice versa.
Biofilms for bacteria and parasites have the same effect, they provide a matrix that protects them from your immune system and any agents you use to eliminate them. Thus, probably one of the reasons that so many people struggle with things like chronic urinary tract infections, h pylori, chronic sinusitis, and lung issues.
It is believed that a substantial percentage of all human microbial infections include biofilms and that Candida biofilms are increasing in frequency and severity. It is estimated by the National Institutes of Health that nearly eighty percent of chronic microbial infections involve colonies of biofilm.
Biofilms of all kinds are considered to be a significant contributing factor to many chronic health conditions and diseases like Lyme, autism, depression, anxiety, adrenal fatigue, autonomic nervous system dysfunction, chronic stress, chronic fatigue, cognitive decline or impairment, irritable bowel, attention deficit, hyperactivity, OCD, chronic urinary tract infections, recurrent strep infections, colitis, Tourette’s, pandas, self-injury and any persistent dysbiosis issue.
They have been implicated in a wide variety of conditions such as peptic ulcers, h pylori, Lyme, otitis media (children’s recurring earaches), chronic low-grade infections of many kinds, gingivitis periodontics, biliary tract infections, osteomyelitis, tonsillitis, sinusitis, bacterial prostatitis, bacterial endocarditis, (infection of the inner surface of the heart and valves), cystic fibrosis, cystitis, and Legionnaire’s disease.
The presence of a biofilm may explain why so many people do not test positive for Candida, bacteria or parasites in many laboratory tests designed to diagnose these conditions, despite the fact that they exhibit all the symptoms of overgrowth. The microbes are able to evade detection in the stool, blood, etc., by hiding in the matrix and antibodies are not produced because the immune system doesn’t recognize them.
It’s also important to be aware that the healthy microbes in our gut also form a biofilm, so we want to be careful not to destroy them. Unfortunately, the biofilm of the resistant and unhealthy organisms overpowers the healthy ones and prevents them from flourishing. We want to restore balance to our normal gut flora and their biofilm. In contrast to an unhealthy biofilm, a healthy biofilm consists of a thin, moist, lubricated, and non-inflamed mucus that permits the transit of nutrients through the gut wall.
Dr. Anju Usman, one of the leaders in the field of biofilms, has found that all their patients who are non-responders to traditional treatment for microbes have biofilm in their blood. You can learn more about how to destroy biofilms, as well as all the other steps that are needed in order to reduce yeast overgrowth in my eBook, Candida Secrets.
The world of biofilms is a very exciting aspect of Candida and other organisms; research in this area may eventually open the door for resolving many resistant cases of not only Candida, but parasites and bacteria as well. New discoveries are happening all the time.
However, do keep in mind that all protocols and work in regard to biofilms is in its infancy and still being explored. Therefore, not all pieces of the puzzle have been discovered yet and results will vary from person to person. Any biofilm or Candida protocol should only be done under the supervision of a physician. However, here are some products that are commonly used successfully.
References
- D. M. Kuhn, T. George, […], and M. A. GhannoumAntifungal Susceptibility of Candida Biofilms – Unique Efficacy of Amphoetericin B Lipid Formations and Echinocandins. Antimicrobial Agents and Chemotherapy. 2002 June ;46(6) 1773-1780
- Al-Fattani MA, Douglas LJ. Biofilm matrix of Candida albicans and Candida tropicalis: chemical composition and role in drug resistance. J Med Microbiol. 2006 Aug;55(Pt 8):999-1008.
- Gordon Ramage, Stephen P. Saville et al. Candida Biofilms: An Update. Eukaryotic Cell, April 2005 vol. 4 no. 4 633-638.
- David G. Davies and Cláudia N. H. Marques. A Fatty Acid Messenger Is Responsible for Inducing Dispersion in Microbial Biofilms? Journal of Bacteriology. March 2009 vol. 191 no. 5 1393-1403
- Dr. Anju Usman. Biofilm Protocol.
- El-Feky MA, El-Rehewy MS, Hassan MA, Abolella HA, Abd El-Baky RM, Gad GF. N-Acetyl Cysteine Reduces Biofilm Formation. Pol J Microbiol. 2009 September 58(3):261-7.
- Center for Biofilm Engineering. Biofilm Basics.
- J. Dafhne Aguirre, Hillary M. Clark, Matthew McIlvin, et al. A Manganese-rich Environment Supports Superoxide Dismutase Activity in a Lyme Disease Pathogen, Borrelia burgdorferi. March 22, 2013 The Journal of Biological Chemistry, 288, 8468-8478.
