380+ Ways To Inhibit Biofilms

Inhibiting Microbial Armor (Bacterial and Fungal)

Biofilms (sometimes described as "cities for microbes") are glue-like membranes produced by microbes (bacteria, fungi and yeasts) to protect themselves from being discovered by our immune system, among other functions (described below). R

In this post, we're going to go over what diet and supplements (as well as advanced techniques) can be used to prevent and/or kill unwanted biofilms from common bacterial and fungal pathogens.

Contents:

  1. What Are Biofilms And Why Do They Form?
  2. How Do Bacteria Communicate?
  3. Benefits Of Biofilms
  4. Downsides Of Biofilms
  5. Biomarkers
  6. How To Inhibit Biofilms With Diet
  7. Probiotics That Inhibit Pathogenic Biofilms
  8. How To Inhibit Biofilms With Bioactive Components
  9. Supplements, Herbs, and Oils That Inhibit Biofilms 
  10. Drugs That Inhibit Biofilms
  11. Pathways To Inhibit Biofilms
  12. Devices And Treatments That Inhibit Biofilms
  13. Other Ways To Inhibit Biofilms
  14. What Increases Biofilm Formation?

What Are Biofilms And Why Do They Form?

 
https://academic.oup.com/femspd/article-lookup/doi/10.1111/j.1574-695X.2011.00858.x

https://academic.oup.com/femspd/article-lookup/doi/10.1111/j.1574-695X.2011.00858.x

 

All microbes either fight each other for survival or work together symbiotically. R R R R R R R

Biofilms serve 4 purposes:

  1. Attach itself to cell surfaces R
  2. Form more colonies and microcolonies (using quorum-sensing, which acts like a language system) R R R
  3. Transfer nutrients in between bacteria (or other microbes) R
  4. Protect the microbes (creating peptides, maintaining oxygen levels, pH, cell density, gene expression) R R

Bacteria's ability to attach to cell surfaces is mediated by surface proteins (pili or fimbriae) and specific exopolysaccharides (EPS). R R

EPS can also act as barrier to protect the bacteria from antimicrobial damage. R

The surface of some bacteria is held together by fibrinogen, fibronectin, and collagen. R

Both Gram-negative and Gram-positive bacteria can form biofilms, as well as some fungi. R

The most common biofilm-forming pathogens include: 

  • Candida albicans R
  • Borrelia burgdorferi sensu lato R
  • Enterococcus faecalis R
  • Escherichia coli R
  • Klebsiella pneumoniae R
  • MARCoNs R
  • Porphyromonas gingivalis R
  • Proteus mirabilis R
  • Pseudomonas aeruginosa R
  • Staphylococcus aureus R R
  • Staphylococcus epidermidis R R
  • Streptococcus viridans R

They can affect systems and services such as: 

  • Aquatic Systems and Drinking Water R R
  • Food and Dairy Industries (such as causing food poisoning) R R
  • Implants R
  • Living Tissue (see more below) R
  • Medical Devices R R
  • Tooth Surfaces R
  • Water Pipes R

How Do Bacteria Communicate?

Bacterial growth is broken into 3 parts: R

  1. Exponential phase (where bacteria accumulate)
  2. Stationary phase (quorum sensing)
  3. Death phase 

Quorum sensing (QS) is essentially the way single cell organisms (such as bacteria) use to communicate that there are other bacteria of the same species around. 

QS is also one mechanism by which bacteria communicate to make biofilms. R

Through QS, bacteria release signalling molecules, autoinducing peptides (AIPs) for gram-positive bacteria and acyl-homoserine lactones (AHLs) for gram-negative bacteria, that bind to other bacteria's receptors. R

Once there are enough AIPs or AHLs (dependent on S-adenosylmethionine, SAM) that reach a certain threshold of density in the area, then the bacteria collectively can execute gene transcription (release toxins, create biofilms, etc). R R

This can cause a positive feedback loop to keep growing, create more toxins and more biofilms. R

So one way (heavily debated) to inhibit biofilm formation is by inhibiting QS (by either hyperactivating or deactivating mechanisms such as TolC, NorE or AcrAB) and the accumulation of AIPs and the dividing of bacteria. R R R

Benefits Of Biofilms

Biofilms can protect our own commensal bacteria.

They make sure commensal bacteria stick to our mucous lining (like secretory IgA or sIgA). 

For example, sIgA influences the composition of the intestinal microbiota (by producing biofilms to protect good bacteria and fighting off bad bacteria). R 

They also help bacteria communicate and express genes together (through LuxI/LuxR). R

For example, if commensal bacteria have a pathogen in the system, they all express the same gene to try and create anti-microbial peptides to fight that pathogen. R

Downsides Of Biofilms

Biofilm Resistance 

 
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5427689/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5427689/

 

Biofilms can make antibiotics useless. R

Biofilms have increased antibiotic resistance and are involved in many persistent diseases. R

Glycocalyx of both gram-negative and gram-positive bacteria help the bacteria stick to a surface and help bacteria mature, essentially making it a lot easier for bacteria to live in harsh environments. R R R R

Heavy metal exposure may also support biofilm resistance. R

Limiting bacteria to nutrients can also slow their growth, which can cause bacteria to be less susceptible to antimicrobial agents and more resistant to antibiotics. R R R R

That is one reason why a low FODMAP diet doesn't work well during SIBO, since when bacteria don't have food, they can turn dormant and hide in biofilm. R 

Bacteria can also go into dormancy and mutate, which can effectively change their intracellular redox potential and make them more resistant to oxidizing agents (like antibiotics) and other stressors. R R

For example, in an adaptive response, inducing E. Coli to heat or starvation can cause it to be resistant to UV or hydrogen peroxide. R

Persister cells if not destroyed can recreate biofilms and cause biofilm/antibiotic resistance. R

Certain antibiotic-resistant bacteria strains can either lack or over express outer membrane proteins, which essentially block anti-microbials action against them. R R

Also, bacterial efflux pumps can become multidrug resistant. R

 
https://www.hindawi.com/journals/ijmicro/2012/528521/

https://www.hindawi.com/journals/ijmicro/2012/528521/

 

Yeasts and filamentous fungi biofilm have similar mechanisms (density, stress, QS, persisters, ECM, efflux, dormancy, overexpressed targets, and the general physiology) to bacterial biofilms. R R

Immune Response to Biofilms

Bacteria that escape from biofilms can spread to other organ systems and become sources of persistent and chronic infections. R R

Biofilms can persist for long periods of time (months to years) without being detected by the immune system. R

Not properly getting rid of biofilms can lead to chronic infections in:

  • Bones (causing bone loss) R
  • Brain (such as Alzheimer's Disease) R
  • Ears R R
  • Eyes R R R
  • Gastrointestinal (such as IBS and SIBO) R R
  • Genitourinary (such as Chronic UTIs and Kidney Disease) R
  • Nasal Cavity (such as CIRS) R
  • Nervous System (such as Lyme Disease) R
  • Oral/Dental (such as Cavities, Gingivitis, Periodontitis, and Tooth Decay) R R
  • Respiratory (such as Asthma, Bronchitis, sinus infections) R
  • Sex Organs (such as Vaginosis and Prostatitis) R R
  • Skin (such as Acne) R R
  • Spinal Tissue R
  • Wounds R

Biofilms may also make our antioxidant system weaker by dampening NRF2 activity. R

Biomarkers

In a model of biofilms associated with SIBO: R

  • IL-1b
  • IL-1ra
  • IL-6
  • MMP3
  • MMP8
  • MMP9
  • NGAL
  • TIMP1
  • TIMP2

In patients with biofilm-related implant infections: R

  • CCL3
  • IFN-gamma
  • IL-8 R
  • MIP1alpha
  • MIP2alpha
  • MRP14

Other biomarkers:

  • TNF-alpha R

These tests can be ordered here

How To Inhibit Biofilms With Diet

 
https://link.springer.com/article/10.1007%2Fs00203-015-1148-6

https://link.springer.com/article/10.1007%2Fs00203-015-1148-6

 

Biofilms can be inhibited by a lot of things ranging from foods, supplements, fatty acids, peptides, small molecules, polysaccharides, nitric oxide, anti-biofilm surfaces, and ionic liquids to name a few. R R

Diet

Hydrochloric acid and bile help prevent biofilm formation (depending on bacterial strain pH). R R R

These foods have the active compounds that inhibit biofilms: 

Probiotics That Inhibit Pathogenic Biofilms

 
 

Bacteria that degrade pathogenic bacterial biofilms:

How To Inhibit Biofilms With Bioactive Components

 
 

Anthocyanins, coumarins, flavanoids, and tannins are all contain powerful bioactive compounds that can inhibit or degrade biofilms. R

Anthocyanins:

Coumarins:

  • Coladonin R
  • Coumarin R R
  • Dihydrocoumarin R
  • Esculetin R
  • Esculin R
  • Nodakenetin R
  • Psoralen R
  • Umbelliferone R

Flavanoids:

Tannins:

Supplements, Herbs, and Oils That Inhibit Biofilms

 
 

Various other natural supplements, herbs, TCM, oils, etc that prevent, inhibit, or degrade/prevent biofilms/QS:

Drugs That Inhibit Biofilms

Drugs and antibiotics that work on biofilms:

  • Amphotericin B R
  • Aryl Rhodanines (MBX-1240, MBX-1246, MBX-1384, and MBX-1427) R
  • Atranonin R
  • Bactroban R
  • Beta-Lactam Antibiotics (not strong and may form biofilms, see belowR
  • Calcium and Magnesium Chelators R
  • Caspofungin R
  • Cefotaxime R
  • Ceragenin R
  • Daptomycin (as last resort) R
  • Farnesol R
  • Finasteride R
  • Gentamicin R
  • Gentian Violet R
  • Linezolid R
  • Ibuprofen R
  • Macrolides (such as azithromycin) R R
  • Methylene Blue R
  • Micafungin R
  • Minocycline R
  • Norgestimate (and 17-Deacetyl norgestimate) R
  • Oxacillin R
  • Phendione R
  • Plectasin R
  • Rifampin R
  • Scandenin Diacetate R
  • Simvastatin R
  • Surfactin R
  • Tigecycline R
  • Trimethoprim (Sulfamethoxazole) R
  • Vancomycin R

Devices And Treatments That Inhibit Biofilms

 
 

Some devices/technologies that inhibit biofilms:

Pathways To Inhibit Biofilms

 
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5142822/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5142822/

 

Pathways and mechanisms in either humans or bacteria/fungi:

  • Increase Acetylcholine R
  • Increase α-Amylase (and other Glycoside Hydrolases) R R
  • Increase α-MSH R
  • Increase ClpP R
  • Increase Dispersin B R
  • Increase DNase I (and other Deoxyribonucleases) R R
  • Increase Hep-20 R
  • Increase LapA R
  • Increase mTOR R
  • Increase Nitric Oxide R R R
  • Increase NRF2 (may prevent formation of biofilms) R
  • Increase NRG1 R
  • Increase Paraoxonases (PON1, PON2, and PON3) R
  • Increase PLUNC R
  • Increase PPAR-gamma R
  • Increase ROS (possibly acutely against Candida) R R
  • Increase SAL-2 R
  • Increase YWP1 (of P. aeruginosa against CandidaR
  • Inhibit AhpA (only during growth phases) R
  • Inhibit Autoinducer 2 (AI-2) R
  • Inhibit bfiSbfmR and mifR R
  • Inhibit Cardiolipin R
  • Inhibit cAMP R R
  • Inhibit Cyclic di-GMP (like ABC-1) R R
  • Inhibit FLO1 R
  • Inhibit PqsD R
  • Inhibit Quorum-Sensing (QSI) R R
  • Inhibit relA R
  • Inhibit RNAIII peptide  (RIP) R R
  • Inhibit SdrC R R
  • Inhibit spoT R
  • Inhibit Staphylococcal Accessory Regulators (such as SarABI) R

Other Ways To Inhibit Biofilms

Other ways to inhibit biofilms:

  • #G43 (inhibits S. mutans) R
  • 2-Aminobenzimidazole R R R
  • 2-Methacryloyloxyethyl Phosphorylcholine (MPC) R R
  • 5-Benzylidene-4-oxazolidinones (inhibits MRSA) R
  • Anthraquinone (Emodins also inhibit biofilms found in some plants, molds and lichens) R R R R
  • Bamboo Fiber R
  • Bee Vemon R
  • Bgugaine (found in Arisarum vulgare, may be toxic to the liver though) R 
  • BpiB05 R
  • Bromide R
  • Bromoageliferin and Oroidin (from sponges) R
  • Caripyrin R
  • Carolacton (good against dental caries) R R
  • Casbane Diterpene (from Croton nepetifolius)_R
  • Cahuitamycins (from marine algae) R
  • Chlorine R
  • Cis-2-decenoic acid (from P. aeruginosa breaks down biofilms from E. coli, K. pneumoniae, P. mirabilis, S. pyogenes, B. subtilis, S. aureus, and C. albicans) R
  • D-enantiomeric peptides R
  • Deacylated Lipopolysaccharides (daLPS) R
  • Decanediol R
  • Dehydroabietic Acid R
  • Dpo7 R
  • Diketopiperazines (strong) R
  • Dimethylaminohexadecyl Methacrylate (DMAHDM) R R
  • Fluoride R R
  • Gallium R
  • Gold R R
  • Kingella kingae (produces galactin which inhibits Aggregatibacter actinomycetemcomitans, K. pneumoniae, S. aureus, S. epidermidis and Candida albicans) R
  • LL-37 (comes from bacteria) R
  • Menthyl carbamate R
  • PelAh (inhibits P. aeruginosaR
  • Peptide 1037 R
  • Petiveria alliacea (contain sulfur derivatives like S-phenyl-l-cystein sulfoxide and diphenyl disulfide) R
  • Proteinase K R
  • Pseudomonas aeruginosa (inhibits Aspergillus fumigatus) R
  • Pyocyanin Demethylase (PodA) R
  • S. mutans (inhibits Candida) R
  • Sph3h (inhibits A. fumigatus) R
  • Thiophenone R
  • Toluidine Blue R
  • Titanium and Copper Oxides R
  • Trimethylsilane R
  • Urea (and other Anti-Matrix Molecules such as Rhamnolipids) R R
  • Xanthomonas campestris (Xcc, by increasing endo-beta-1,4-mannanase) R
  • Zosteric Acid R

What Increases Biofilm Formation?

  • Beta-Lactam Antibiotics (through resistance) R
  • Doxorubicin R
  • Dysbiosis R R R
  • Galactose (Raffinose has the opposite effects) R R
  • IL-10 (in staphylococcus aureus) R
  • Infrared (Independent of LLLT) R
  • Iron R
  • Lectins (partially) R R
  • Nicotine R R
  • NSAIDs R
  • Rifampicin (lower doses) R
  • Salt R R
  • Sugar (glucose is okay but sucrose isn't) R R
  • Vaginally Inserted Devices R