Biofilm is ubiquitous - and also likely plays a role in resistance to chronic lyme treatment.
Chronic lyme biofilm
Chronic lyme biofilm may be an important component in comprehenive treatment for patients with chronic lyme disease. Just this last weekend at the ILADS scientific meeting in Toronto, Dr Sapi, PhD from the University of New Haven presented her data from microscopic studies of lyme.
There were a few interesting observations in this lecture. Firstly, Dr Sapi is the one who haspublished in peer-reviewed journals different lyme killing concentrations of different antibiotics. This was originally done by culturing lyme in a lquid suspension, and then assessing different antibiotics and the concentrations needed to kill the bacteria.
I had read the study quite a wihle ago and also her recent update, but the back story she gave at the conference was quite interesting. She had her graduate students repeat the studies so that she could confirm the data. Dr Sapi mentioned that graduate students often "don't follow instructions" and by chance, instead of culturing the borrelia (lyme causing germ) in a suspension, they did it in closed little wells with more surface (kind of like a plate instead of a vial).
Dr Sapi mentioned that the data produced on concentrations of antibiotics needed to kill lyme was much greater, sometimes 1000 fold greater, when the borrelia was cultured in the plate method.
There were two explanations. The first is directly applicable to what I see in my own practice. One was that oxygen exposure to Dr Sapi's original samples was much greater. We do know from other studies that lyme does not tend to like oxygen, and may be more susceptible to antibiotic killing with oxygen exposure. The increased oxygen exposure may have allowed for more clinically achievable, eg achievable in patients, levels of antibiotics to be effective.
This may explain some of the anecdotal experience that I have seen, in that many chronic lyme patients being treated with antibiotics either from another physician or myself, do much better or even only start to respond after we add in ozone therapy with or without UV irradiation As a side note, Dr Bock from New York also spoke in the Q and A of his own similar knowledge that patients who were treated with UV therapy with ozone tended to do much better, in multiple infections, not just in lyme. He mentions correctly that UV irradiation was previously used to treat even an acute blood infection such as sepsis. He also gave an interesting case study of a patient who had failed multiple previous treatments and was much improved to cured after a long series of at first twice weekly, then weekly, ozone treatments. This is very similar to some of my own patients, even a few who have done well without antibiotic therapy.
Back to the chronic lyme biofilm, Dr Sapi's main point about her graduate students accidental finding was actually not about oxygen, but about bioflim itself. She presented a series of slides that she took while further investigating the differences between the two culture methods. It was very clear that at least in experimental conditions, lyme made very biofilm structures. They were communities of organisms that exuded a protective matrix of gel, with rigidity, that protected them from lower levels of antibiotics.
It is still very true that it is not known beyond a doubt whether or not lyme biofilm exists in patients. It does in test tube environments, but no one has shown that lyme biofilm is produced in humans. There is a lot of anecdotal data, and suggestive data from labs such as Fry Labs, (I have run such tests as well), but in those smears of blood we don't know if lyme is the main organism, and in fact preliminary information suggests it is actually a coinfection that is the main bug in there.
Dr Fry did give a good talk recently about biofilm in nature and in humans, which accompanied a talk on increased blood viscosity and hypercoagulability (increased clotting) - the two of them often go hand in hand.
Biofilm, including chronic lyme biofilm, is a slime that bacteria and other germs make to protect themselves. In nature, biofilms are the rule, rather than the exception. Dr Fry speaks also of the CDC estimating that 70-80% of infections are biofilm based. As mentioned above, we don't actually know if chronic lyme biofilm is one of these, but my patients do seem to often need biofilm treatment.
Common examples of biofilm include dental plaque, or in nature, the slime that we can see around a pond or stream. What is really interesting though is that the same germ will turn on different genes when it is alone vs when it is in a biofilm community. Chronic lyme biofilm is likely the same, giving implications when using treatment with drugs.
The structure of biofilm includes DNA, the minerals iron, calcium, magnesium, and it has proteins and lipids. There are molecules that serve as "quorum sensing" and help the germs to communicate with each other. The DNA serves as the "rebar" in the biofilm matrix, giving it rigidity and structure (Dr Fry). Dr Sapi mentioned that in her test tube studies of chronic lyme biofilm, there was a similarity between E coli biofilm and chronic lyme biofilm in that both had a carbon to nitrogen bond, which is very rigid and strong. A question that popped into my mind is whether that bond is susceptible to breakage or hydrolysis by peroxides, which are formed in ozone therapy.
Some of Dr Fry's work was particularly interesting in that in the past, we were that that if you could not culture an infection, it is not there. This is definitely not true in biofilm based infections as many of the organisms in such films can not be cultured out.
In diseases such as chronic sinusitis, it is interesting that ENT doctors will often literally scrape out the infection and pus, which is a mechanical way of clearing out biofilm. And patients get relief. If chronic lyme biofilm exists in patients, there wouldn't be such a simple solution as of course the chronic lyme biofilm would not be localized to one tissue.
Another interesting study looked at otitis media (middle ear infection) and in 46/50 children, biofilms were observed, vs none being seen in the controls. The germs found in the biofilm were the typical culprits when the middle ear infection gets infected with bacteria, such as Haemophilus influenzae, streptococcus pneumoniae, moraxella catarrhalis. What is interesting is the clinical observation that most symptomatic middle ear infections actually appear to be viral, but that if the viral infection is not self limited (clears on its own) then sometimes a bacterial infection can become predominant and antibiotics may be useful. Who knows whether or not the bacteria were present from the start, in biofilm (and thus harder to culture) and were just cleared by the immune system alone.
There is some precedent for biofilm treatment in patients, though not yet in chronic lyme biofilm. In cystic fibrosis patients, biofilm is a well-known phenomena, and the daily use of azithromycin (an antibiotic) improved outcomes in that the patients lived longer.
There also was a lot of older data on nanobacteria and there role in producing calcium oxalate kidney stones (which may be a form of biofilm, just with a lot of calcium!). Some studies showed benefit with a combination of EDTA (a chelator I use a lot of intravenously) and tetracycline (an antibiotic).
There is evidence that chronic cystitis (chronic bladder infections) are biofilm based E coli colonies. There is evidence that chronic non-healing wounds have biofilm based organisms growing, and thus multiple antibiotics are needed. This would likely apply in chronic lyme biofilm, as already most patients with chronic lyme require multiple antibiotics in their treatment.
Chronic lyme biofilm, if it exists in patients (and I think it does), is a strong promoter of inflammation. We know that the slime layer protects the whole complex, and the immune system recognizes it but can not eliminate it.
Dr Fry did discuss some of the treatment strategies that he has found to be helpful. Remember he is a general practice doc with a lab as well, and that I use his lab to identify whether or not some biofilm is present in patients. Again, we don't know if lyme is the main bug in the film, and it seems like it may not be, but it is still likely a component. Dr Fry's strategies mentioned included enzymes (wobenzym PS, nattokinase, serrapeptidases, and lumbrokinase / boluoke), multiple antbiotics, honey, bismuth thiols, herbs, and mechanical measures. The honey one is interesting, in some European countries you can get gauze impregnated with honey and it seems to be very effective for these chronic biofilm related wounds. As a side note - there apparently is another honey that is 10x more potent than manuka honey on biofilm, which I will have to follow up on.
EDTA chelation has interesting results as well. Greenburg did a study looking at EDTA chelation induced killling and dispersal of pseudomonas biofilm. He tried the EDTA alone, or an antibiotic called gentamycin, or the combination. In this test tube study, neither agent alone killed the biofilm but the combination did.
I have tried EDTA augmentation of oral antibiotics in some of my patients who I suspect of having chronic lyme biofilm, but with no results so far. I have had better results in such suspected patients using the enzymes to help with chronic lyme biofilm, (though admittedly they have a lot of anti-inflammatory effects on their own), and with ozone therapy.
Another interesting point brought up by Dr Fry was the liberation treatment work done on multiple sclerosis by Dr Zamboni. This is the one you have read about, which is where some MS patients seem to have narrowed neck veins, and the treatment is using a catheter to expand the neck veins. There may be a biofilm component to this. Dr Fry showed a video of the internal carotid vein, and its narrowing on ultrasound which also showed strands of that narrowing hanging into the lumen of the vessel. That looks awefully like biofilm, as a plain structural narrowing does not have strands protruding down. The catheter expansion may actually be scraping biofilm off. Perhaps sometimes recurrences happen (if it works for the patients in the first place) because continued treatment of inflammation or infection does not happen after the procedure.
At any rate, there is no doubt that chronic lyme biofilm exists in experimental conditions. We don't know yet if chronic lyme biofilm exists in human patients, but I believe it does. There was similar debate before about whether or not the cystic form of lyme exists in patients, with some doctors believing it to be only important in lab studies. Dr Alan Macdonald's work with slides of brain tissue in Alzheimer's proved that that cystic form of lyme exists in humans. Likely, the same will eventually be shown for chronic lyme biofilm.