Healthy Flora, Biofilms And Chronic Gastrointestinal Dysbiosis

The Silent Role of Biofilms in Chronic Disease Forums Biofilm Community Introduction to Bacterial Biofilms Healthy Flora, Biofilms And Chronic Gastrointestinal Dysbiosis

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        By Anju Usman, M.D.


        Patients who are chronically ill and under chronic stress often have a weakened immune system that puts them at risk for developing infections. It is the responsibility of our gastrointestinal (GI) tract to be the first line of immunity against pathogens from the outside world. We are all supposed to have an abundance of healthy, symbiotic flora growing in our GI tract called microbiota. The good bacteria in our body help us to fight off pathogens and allergens. When the balance of good bugs and bad bugs is disrupted, our immune system cannot develop or function optimally, and chronic infections, allergy, inflammation, autoimmunity and chronic illness may ensue. This overgrowth of bad microbes in the gut is referred to as dysbiosis. Treating dysbiosis with tools such as antibiotics, antifungals, special diets, probiotics (live good bacteria), digestive enzymes and targeted nutrients can be extremely effective. Patients often report improvement in physical – and even mental – symptoms quickly.

        However, for some of our patients, these treatment strategies may not work or are no longer effective. In order to help this subset of patients, we need to expand our thinking and look at new concepts about how microbes survive and create disorder in our bodies.


        Luckily, our old concepts of microbiology are rapidly being replaced with newer, more sophisticated paradigms. In fact, scientists worldwide are now viewing masses of microorganisms as evolved, complex colonies that have developed unique and intricate ways to survive and evade our immune system. Bacteria are now found to have an underlying social intelligence. They actually cooperate with one another to solve challenges by using a unique architecture that allows communication between the cells. Bacteria also communicate with one another via signaling molecules called quorum-sensing molecules. These molecules drive bacterial gene expression and regulate conjugation, virulence, resistance, biofilm formation and motility.


        The gut harbors the largest collection of microorganisms in the human body. In fact, there are over a trillion bugs that reside in our GI tract. In 2007, the National Institutes of Health launched the Human Microbiome Project, a five-year, $140 million effort to study and explore how the trillions of microscopic organisms in our bodies affect our health. Dr. Vincent Young, a researcher from the University of Michigan, states, “The gut ecosystem needs to be preserved and that changing the ecosystem through stresses such as antibiotics could irreversibly change the ecosystem, with deleterious effects.” Dr. Young has studied the effects of antibiotics on the microbes in
        our gut. He found that mice given particularly strong antibiotics had all their normal gut microbes completely wiped out.

        Even more striking, Clostridium species and fungal species were then able to overgrow without the good bacteria there to fend them off. As in mice, once the bad bugs take hold in our GI tract, they may be difficult to eradicate. Taking appropriate probiotics and eating nutritious, non-toxic, antibiotic-free food can help renew our internal ecology, but sometimes we remain unsuccessful in restoring our natural flora. One possible explanation for this persistent dysbiosis may be due to the production of pathogenic biofilm by the bad bugs in our gut.


        A biofilm is a collection of microbes that grow in communities and have a distinct architecture. The unique design of a biofilm is like a tiny city of microbial cells that form a protective extracellular polymeric substance (EPS) or matrix to surround the city. Within this matrix are rivers or channels that bring nutrients, oxygen and other material needed for survival of the colony. The biofilm architecture provides an optimal environment for cell-to-cell interactions, including the intercellular exchange of genetic material, quorum-sensing molecules and metabolites. The protective matrix that surrounds the microbes is composed of negatively charged polysaccharides (sugar), fibrin, and DNA, all held together with the positively charged metal ions calcium, magnesium, and iron. This matrix, in which microbes in a biofilm are embedded, protects them from UV exposure, metal toxicity, acidity, dehydration, salinity, phagocytosis, antibiotics, antimicrobial agents and, most importantly, the human immune system.

        There are two types of biofilm communities: symbiotic and pathogenic. Symbiotic biofilms are produced by our good bugs and protect our gut lining. In fact, many scientists believe that our appendix plays a role in producing our symbiotic biofilm. In the human body, symbiotic biofilm communities protect the mouth, teeth, pancreatic ducts, biliary tracts, lungs, sinuses, adenoids, tonsils and, of course, the GI tract.


        However, when bad bugs overgrow they may also produce a biofilm that is considered pathogenic. These pathogenic biofilm communities adhere to man-made and natural surfaces, typically at a liquid-solid interface. They account for the majority of all microbial infections in the human body and more than 65 percent of hospital-acquired infections. This pathogenic biofilm surrounds and protects the bad bugs like an impenetrable fortress, allowing them to thrive and reproduce. The microbes hiding under biofilm are highly resistant to both immunologic and non-specific defense mechanisms of the body. As the bad bugs reproduce, they continue to pro duce toxic byproducts that may be detrimental to the health of the host without the host even realizing the bad bugs are there. Some microbes even fail to express outer membrane proteins (OMP) when iron is present. When outer membrane proteins are not expressed, the immune system is unable to recognize pathogens and, therefore, is not able to produce antibodies against the bugs.


        The pathogens living in biofilm are remarkably difficult to treat, often resistant to doses of antimicrobials, and 100- to 1000-fold over the minimum lethal dose for microbes outside of biofilm. Since the bacteria hiding under biofilm is difficult to see and culture and since the immune system may not be producing antibodies against the pathogens, the bad bugs can be very difficult to diagnose. However, a history of the following may indicate the presence of pathogenic biofilm:

        • persistent or recurrent dysbiosis
        • chronic sinusitis
        • otitis
        • bronchitis
        • tonsillitis
        • dental caries
        • cystitis
        • chronic gingivitis
        • patient initially does well with antibiotics and antifungals but later becomes resistant
        • history of frequent antibiotic use or antibiotic use at a very young age
        • patient does well when placed on antifungals/antibiotics even though cultures are negative and relapses when antifungals/antibiotics are stopped


        Recently, scientists have been discovering ways to penetrate these pathogenic biofilms and expose the bad bugs beneath so that they can be addressed by the immune system. Probiotics, prebiotics, synbiotics, oral NaEDTA, iron chelating compounds (lactoferrin), chitosans as well as mucus and fibrin degrading enzymes all have the potential to help antimicrobials work with better efficiency to restore the balance of good bugs in the body. Enzymes, in particular, have a long history of safety and efficacy in helping patients with a variety of issues.

        Kirkman’s Biofilm Defense contains a combination of unique enzymes that have the ability to dissolve the polysaccharide and fibrin components of biofilm. Because this enzyme lacks any significant amount of protease, which can irritate a sensitive GI tract, Biofilm Defense TM can be taken on an empty stomach. In fact, it may be recommended by clinicians to use this product on an empty stomach followed by appropriate natural or pharmaceutical antimicrobials that target a specific bug or bugs residing in biofilm.

        This enzyme should be used with other aforementioned strategies – in particular, high quality, high potency probiotics and prebiotics. Prebiotics, which consist of fiber that is fermented in our gut, help fuel the cells that line the GI tract. Proper digestion of fats, carbohydrates and protein is essential to prevent putrefaction and further bacterial overgrowth in the bowel. Digestive enzymes taken with food may also be needed to support this process. After all, our goal is to restore the gut ecology and our symbiotic biofilm to its natural state.


        It requires more than just recognizing a pathogen and killing it to help heal the gut. It also requires a healthy, nutritious diet, high in fermented fiber (prebiotics), that fuels the cells that line the gut (enterocytes). Nevertheless, the key still remains the ability to repopulate the normal gut flora. This may be accomplished by using a variety of high quality, high potency probiotics and cultured foods.
        The ecology of the gut still remains, in large part, a mystery to us. We are just beginning to learn about the variety and roles of the multitude of species growing inside of our GI tract. So far we have underestimated the importance of the good bacteria in our body. In the future, the strategies we employ to restore our body’s ecology will be paramount to reclaiming our healthy bodies and healthy minds.

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        2 Falcdo, J., et al. Cell-to-Cell Signaling in Intestinal Pathogens. Curr Issues Intest Microbiol. Mar 2004; 5:9-18.
        3 Macfarlane, S. et al. Composition and Metabolic Activities of Bacterial Biofilms Colonizing Food Residues in the Human Gut. Applied and Environmental Microbiology. 2006 Sept; 72(9):6204-6211.
        1 Collins, M. et al. Probiotics, Prebiotics, and Synbiotics: Approaches for Modulating the Microbial Ecology of the Gut American Journal of Clinical Nutrition. 1999 May, 69(5);1052S-1057S.
        -1 Macfarlane, S. et al. Microbial biofilms in the human gastrointestinal tract. J Appl Microbiol. 2007 May, 102(5):1187-96.
        6 Kim, H-J et al. The efficacy of ethylenediaminetetraacetic acid (EDTA) against biofilm bacteria. Carnegie Mellon University.
        7 Singh, P.K., et al. A Component of Innate Immunity Prevents Bacterial Biofilm Development. Nature. 2002 May 30; 417(6888):552-5.
        8 Lu, T. et al. Dispersing biofilms with engineered enzymatic bacteriophage. Proc Natl Acad Sci USA. 2007 Jul 23;104(27):11197-202.
        I Selan L. et al. Proteolytic enzymes: a new treatment strategy for prosthetic infections? Antimicrob Agents Chemother. 1993 Dec, 37(12):26182621.
        10 Akiyama H. et al. Biofilm formation of Staphylococcus aureus strains isolated from impetigo and furuncle: role of fibrinogen and fibrin. J Dermatol Sci. 1997 Nov.
        Sumi, H. et al. Enhancement of the Fibrinolytic Activity in Plasma by Oral Administration of Nattokinase. Acta Haematol. 1990;84(3):139- 43.

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