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biofilms
Biofilms occur when highly organized communities of microorganisms, primarily bacteria and fungi in the gastrointestinal tract adhere to surfaces and produce a self-created protective environment known as the extracellular polymeric substance (EPS) [1]. Consider this a slimy matrix encapsulating these organisms in a bubble-like structure.
Biofilms are composed of sugars, proteins, lipids, and extracellular DNA, and serve multiple functions. They help bacteria and fungi stick to surfaces, shield them from antibiotics and antimicrobials, and also protect them against the immune system.
The biological process of biofilm development follows several stages. Initially, planktonic (free-floating) microbes loosely attach to a surface. Upon sensing the surface these microorganisms then express genes that strengthen adhesion and initiate EPS production. EPS, along with other components forms the biofilm matrix, which then supports the growth of microbial colonies under the protection of their shield [2].
A critical feature in Biofilm development relies on the density of microbial populations behind it. Consider it as strength in numbers, when a large population of bacteria decide to act together they begin processes of chemical communication, known as quorum sensing. Quorum sensing coordinates behavior and switches on or off specific genes. This communication is essential to the formation of biofilms. [3].
Biofilms have importance in human health and while some biofilms are supportive, biofilms protecting pathogenic bacterial organisms are implicated in many health conditions. Therefore biofilms need to be disrupted and broken down, which enables immune detection of harmful organisms, and allows anti-microbial support to be effective in treatment [4].
signs & symptoms
80% of Chronic Infections
Persistent and recurrent infections of all kinds are a hallmark of biofilm involvement, with biofilms estimated to underlie up to 80% of chronic infections. Within biofilm structures, microbes are encased in a protective matrix that is estimated to make them between 10 to 1000 times more tolerant to antimicrobial treatments. [2] As a result, infections may show temporary improvement with treatment only to relapse once treatment stops, since pathogens remain safeguarded deep within the biofilm community.
Examples and clinical reference of biofilm related conditions are detailed below.
Chronic Dermatitis + Eczema
In dermatitis and eczema certain bacteria that normally live on the skin, especially Staphylococcus aureus and Staphylococcus epidermidis are strongly linked to flare-ups. These bacteria often switch into a biofilm state and within these biofilms, the bacteria can block sweat ducts and release signals that activate the skin’s defense pathways. This sets off a chain reaction where TLR2 receptors on skin cells are triggered, which then stimulate chemicals that cause itching and swelling. The result is the cycle of itching, scratching, and rash that characterizes flares. [16]
In a clinical study of 40 people with eczema and 20 controls, researchers found that:
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Staphylococcus aureus made up approximately 42% of the bacteria from lesions
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Staphylococcus epidermidis made up approximately 20%.
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Biofilms were present in 100% of lesions
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100% of biopsies from affected areas showed sweat ducts blocked with biofilm material [16]
Chronic Acne
Acne develops in part due to the activity of Cutibacterium acnes, a bacterium that thrives in the oily, low-oxygen environment of hair follicles. Certain strains of C. acnes are more strongly linked to acne because they release enzymes such as lipases, which break down skin oils into free fatty acids. These fatty acids irritate the follicle lining, while other bacterial products that trigger inflammation and damage the follicle wall. This process leads to the swelling, redness, and pus-filled lesions characteristic of acne.
What makes these strains even more problematic is their ability to form biofilms. Within a biofilm, bacteria cluster together and shield themselves from both the immune system and topical antimicrobial or cleansing treatments. In this state, they not only survive longer but also produce more inflammatory substances, further worsening acne, and preventing complete eradication, causing acne to persist and relapse. [3]
Chronic Candidiasis - Thrush
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Itching and irritation
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Burning sensation, sometimes worse with urination or sex.
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Thicker white discharge
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Odourless discharge
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Rashes on warm, sweaty or creased skin
Candida infections tend to become chronic when round yeast cells switch to invasive hyphae that penetrate tissue and establish colonies large enough to build biofilms. Within this biofilm state, Candida upregulates efflux pumps, which actively export antifungal drugs and remodels membrane sterols to reduce drug binding. Together, these changes drive multidrug resistance, leading to persistent, much harder to eradicate infections, which cause greater local inflammation and tissue injury. [4]
Chronic Bacterial Vaginosis
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Little to no itching
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Malodorous / Fishy smelling vaginal discharge
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Discharge thin, milky or grey
Bacterial Vaginosis (BV) is the leading vaginal disorder in women and attributes over 60% of vulvovaginal infections caused predominantly by Gardnerella vaginalis, adherent to vaginal epithelium. Research strongly suggests that biofilm formation is a required early event for BV initiation and progression, which is backed by its high recurrence rate after medical treatment, demonstrating that medications such as metronidazole and Tinidazole regimens cure up to 82% of cases, but recurrence rates within 1 - 2 months are typically between 30 - 40%. [13]
Chronic Rhinosinusitis
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Post Nasal Drip
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Nasal Congestion
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Nasal Discharge
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Sinus Pressure
The bacterial species most commonly associated with chronic rhinosinusitis (CRS) include Staphylococcus aureus, with approximately 50% prevalence in CRS biofilms, Pseudomonas aeruginosa, 22% prevalence, and Haemophilus influenzae 28% prevalence, with other organisms identified to a lesser prevalence including Candida albicans.
To determine the prevalence of biofilms in CRS, 6 key studies evaluated the prevalence of biofilms and demonstrated an overall average prevalence of biofilms for approximately 76% of cases, supporting the view that biofilm-forming bacteria play a central role in CRS. [17]
Recurrent Upper Respiratory Infections
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Colds
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Flu or Bronchitis
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Tonsilitis
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Sinus Infections
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Ear infections
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Conjuntivitis
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Post-infectious cough
Biofilms contribute to chronic and recurrent upper respiratory tract infections by creating a protected microbial community that adheres to mucosal surfaces within a biofilm. Within these biofilms, bacteria communicate via quorum sensing, which allows them to coordinate survival strategies. This structural and biochemical organization blocks the penetration of antibiotics and shields microbes from host immune responses. As a result, pathogens persist despite repeated antibiotic or anti-inflammatory treatment, driving ongoing inflammation and tissue damage.
In a study of 32 surgical specimens from patients with recurrent tonsillitis, adenoiditis, and sinus infections unresponsive to therapy, biofilms were directly visualized in 65.6% of tissues using scanning electron microscopy, and over 80% of samples were culture-positive.[5][6][8]
Chronic Diarrhoea
When researchers looked at patients with diarrhoea prone, irritable bowel syndrome, they found that many had biofilms stuck to the lining of the small intestine and right side of the colon. These biofilms were seen in 57% of patients, compared with only 6% of healthy people.
What makes this important is how biofilms interact with bile acids, the chemicals made by the liver to help digest fats. Normally, bile acids are absorbed back into the body in the small intestine, but in patients with biofilms, the bile acids were trapped inside these bacterial layers. Lab tests showed a buildup of taurocholic acid in the tissue, and stool tests revealed that people with biofilms had twice as much total bile acid and up to a 10 fold increase in primary bile acids compared with people without biofilms. This overflow of bile acids into the colon is known to trigger diarrhea, because bile acids pull water into the gut and speed up bowel movements. [7]
Digestive Disorders + Diseases
In a large cohort study of 1,426 patients with bowel complaints, endoscopically visible mucosal biofilms were observed in the following proportion of cases:
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57% - Irritable Bowel Syndrome (IBS)
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34% - Ulcerative Colitis (UC)
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22% - Crohn’s Disease (CD)
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6% - Healthy Individuals
When the protective mucus barrier of the digestive tract becomes thinned or disrupted, often due to microbial imbalances that allow pathogenic or opportunistic strains to dominate, bacteria can more easily attach directly to the intestinal lining and form biofilm matrices. These biofilms act like a shielded community of microbes, making them harder to clear and creating a persistent source of inflammation. Clinically, this process is strongly linked to conditions such as irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD), both of which show higher mucosal bacterial density compared to healthy individuals [11].
Chronic Gastritis
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Upper abdominal pain, burning, or gnawing discomfort
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Indigestion
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Nausea
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Feeling full or bloated after eating
Chronic Gastritis is tightly linked to Helicobacter pylori infection and to peptic ulcers. Gastric biopsies from 100 patients showed that H. pylori was found almost exclusively in those with active chronic gastritis or peptic ulcers, with the cases of peptic ulcers demonstrating a biofilm formation prevalence as follows
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97% - Helicobacter pylori biofilms in ulcer cases
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1.6% - Healthy Individuals [9][10]
Chronic Fungal Infections
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Tinea pedis - Athlete’s Foot
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Tinea cruris - Jock Itch
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Tinea corporis - Ringworm
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Tinea unguium - Fungal Nail Infection
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Tinea versicolor - Pityriasis Versicolor
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Malassezia-associated conditions - Dandruff
Microscopy studies have confirmed that the dermatophytes responsible for tinea can form dense, multilayered biofilm aggregates that bind tightly to keratin-rich tissues such as the skin, hair, and nails. This means that during a tinea infection, the fungus doesn’t just sit on the surface; it builds a protective, mesh-like structure around itself. These biofilms act as a physical and chemical shield, reducing the penetration of antifungal treatments and helping the organism evade the immune system. Clinically, this explains why tinea infections often become persistent, slow to respond, or recurrent, as the fungal biofilm makes the infection significantly harder to eradicate compared to free-floating (planktonic) fungal cells.
Similarly, Malassezia species can cluster along hair shafts and follicular openings in cohesive biofilm-like formations. These biofilms act as a shield, helping the organisms resist antifungal treatments and evade the immune system, which explains why some tinea or dandruff-related conditions become persistent or recurrent. [26]
Chronic Bacterial Infections
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Paronychia
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Abscesses or Boils
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Folliculitis
Paronychia, abscesses or boils, and folliculitis are frequently associated with biofilm-forming bacteria, particularly Staphylococcus aureus, Staphylococcus epidermidis, various Streptococcus species, and mixed polymicrobial flora. Extensive microbiologic studies demonstrate that these organisms readily produce biofilms that adhere to skin, nail folds, and hair follicles. This biofilm behaviour contributes directly to the persistence, treatment-resistance, and recurrent nature of these infections. [27][28]
Chronic SIBO
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Abdominal Bloating
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Abdominal Distension + Discomfort
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Flatulence and Belching
Biofilm formation in the gut is strongly dependent on microbial numbers. In the stomach and upper small intestine, ordinarily where microbial density is normally very low, only scattered and fragile biofilm fragments can form.
In contrast, in conditions like small intestinal bacterial overgrowth (SIBO), where bacterial numbers in the small intestine rise abnormally, the excess density provides an opportunity for bacteria to adhere, persist, and form biofilm-like communities in a region where they would not normally be sustained. These biofilms stabilize the bacterial overgrowth and protect microbes from clearance, causing advanced SIBO cases to become resistant to antimicrobial treatment. [12]
Recurrent Urinary Tract Infections
Urinary Tract Infections most commonly are an ascending infection from the rectal or vaginal flora into the urethra and bladder. Research on an overview of 16 studies on UTI’s demonstrated that the main pathogens associated with UTI’s are Uropathogenic E. coli in approximately 82% of UTI cases, Enterococcus spp in approximately 63% of cases and other uropathogens in approximately 84% of cases. [14]
These strains of bacteria are very often capable of forming biofilms. In fact, when researchers grew them from patient urine or catheter samples under lab conditions, about 79% of them developed biofilms. Demonstrating that nearly 8 out of 10 UTI prevalent bacterial strains tested could produce a protective layer when placed in a petri dish. [15]
Causes
Bacterial and Fungal Colonization
Biofilm infections begin when bacteria or fungi attach to tissues [13]. Once attached, these microbes start producing a matrix of sugars, proteins, and DNA (the EPS) that glues them to the surface and to each other. The more surface sensing that occurs by microorganisms attaching to the digestive lumen, the more upregulated biofilm-associated genes become, leading to enhanced EPS secretion and stronger biofilms [14,15].
The immune system initially responds with neutrophils and macrophages, but the thick EPS matrix blocks effective attack, creating “frustrated phagocytosis” and chronic inflammation [16]. Clinically, this results in stubborn infections [17].
As an example, research shows that biofilm-embedded Candida albicans cells require antifungal doses 30 to 1000 times higher than free-floating cells for effective killing [18].
Impaired Immune Response
When the immune system is compromised, either due to illness or medications, biofilms can establish themselves much more easily [19].Once established, chronic antigen stimulation by biofilms leads to immune exhaustion, marked by a dysfunctional state in T cells, potentially making them less effective.
Clinically, immune suppressed patients experience higher rates of infections orientated around bacterial and fungal colonization. Animal studies confirm that impaired neutrophil function allows biofilms to rapidly mature and resist even high doses of antibiotics [20].
Medical Devices and Implants
Medical devices like catheters, orthopedic prostheses, and heart valves also provide perfect surfaces for biofilm growth. Body fluids quickly coat these surfaces with proteins like fibrinogen and fibronectin, creating an ideal environment for bacterial attachment and biofilm formation [21].
The immune system has difficulty detecting and clearing biofilms on synthetic surfaces, and macrophages often fail to recognize EPS material as a threat.Clinically, this leads to difficult-to-treat infections on hip replacements, pacemakers, and intravenous catheters, often requiring surgical removal.
Chronic infections and Inflammation
Infections create chronic inflammation, which creates tissue damage. Tissue damage encourages microbial colonizations and biofilm formation. This is because damaged tissues release pro-inflammatory cytokines, which inadvertently support bacterial growth by disrupting natural barriers [42].
In response, the immune system deploys neutrophils and macrophages, but biofilms deflect these attacks, leading to chronic infections.
Animal models demonstrate that tissue injury increases biofilm formation by pathogens like Pseudomonas aeruginosa by up to 10 times compared to healthy tissue.
References
[1] https://pmc.ncbi.nlm.nih.gov/articles/PMC10503651/
[2].https://aricjournal.biomedcentral.com/articles/10.1186/s13756-019-0533-3
[3] https://pmc.ncbi.nlm.nih.gov/articles/PMC8671523/
[4] https://pmc.ncbi.nlm.nih.gov/articles/PMC5816785/
[5] https://pubmed.ncbi.nlm.nih.gov/17083751/
[6].https://www.sciencedirect.com/science/article/abs/pii/S0378517321005731
[7] https://pmc.ncbi.nlm.nih.gov/articles/PMC8527885/
[8] https://pmc.ncbi.nlm.nih.gov/articles/PMC10117668/
[9] https://pmc.ncbi.nlm.nih.gov/articles/PMC11391705/#B431
[10].https://www.gastrojournal.org/article/S0016-5085%2824%2905054-6/
[11] https://pmc.ncbi.nlm.nih.gov/articles/PMC3536164/
[12] https://pmc.ncbi.nlm.nih.gov/articles/PMC9884580/
[13] https://pmc.ncbi.nlm.nih.gov/articles/PMC4718981/
[14] https://pmc.ncbi.nlm.nih.gov/articles/PMC9865985/
[15] https://pmc.ncbi.nlm.nih.gov/articles/PMC8300799/
[16] https://www.researchgate.net/publication/259877428
[17] https://pmc.ncbi.nlm.nih.gov/articles/PMC5698538/
[18] https://onlinelibrary.wiley.com/doi/10.1002/alr.21459
[19].https://researchnow.flinders.edu.au/en/publications/colloidal-silver-a-novel-treatment-for-staphylococcus-aureus-biof
[20] https://pmc.ncbi.nlm.nih.gov/articles/PMC9409202/
[21] https://pubmed.ncbi.nlm.nih.gov/33552621/
[22] https://pmc.ncbi.nlm.nih.gov/articles/PMC8698619/
[23] https://www.nature.com/articles/ijos201452
[24] https://pmc.ncbi.nlm.nih.gov/articles/PMC6425673/
[25] https://pmc.ncbi.nlm.nih.gov/articles/PMC5981455/
[26] https://pmc.ncbi.nlm.nih.gov/articles/PMC9960790/
[27] https://pmc.ncbi.nlm.nih.gov/articles/PMC9854888/
[28] https://pmc.ncbi.nlm.nih.gov/articles/PMC9903335/
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