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Bacteriophage Therapy – Will Phages Replace Antibiotics?

Bacteriophage Therapy

Imagine a 100% natural (and safe) supplement that can selectively destroy several strains of bad bacteria, amplify whatever probiotic supplement you may also be taking, while at the same time feed your beneficial intestinal bacteria? Sounds too good to be true? I thought so too, but read on!

As many of you know I’ve been quick to debunk “alternative” treatments that research shows do not work, especially those likely to do harm. I’ve spoken out against everything from green coffee enemas to Rife machines; I also frequently speak out against supplements that are essential antiseptics and kill our beneficial bacteria. Unless something has some independent research behind it, and passes the biologic smell test, I recommend people avoid it. Not only are many of these treatments likely to be useless, but many are harmful; at a minimum, they waste time, money and energy better spent on better options.

So, when I tell you there is a 100% natural treatment that is very selective in the bacteria that it kills, extraordinarily safe (has FDA “GRAS” status), and is relatively inexpensive, you’re naturally going to be skeptical (at least I hope you are, there are a lot of scams out there).Phages on Bacterium

What is this natural treatment? Bacteriophages, or phages for short.

The literal definition of a bacteriophage is “bacteria eating”, because that is their primary function in life, to reproduce through infecting, and destroying, very specific bacterial strains, and only those strains. A phage is a type of virus that invades and kills bacteria, and only very specific bacteria. You can think of phages as beneficial viruses, just like we have beneficial bacteria. Bacterial DNA and anatomy are vastly diverse, humans have more DNA in common with a bird than some bacteria have with each other! So just like you can’t catch the dog flu virus from Fido, a phage can only infect certain bacterial strains, they can not even harm our good microbiota strains.

So why are phages important? I’ve been reading about phages for many years, and we’ve known for nearly 100 years that phages have great promise for replacing antibiotics. Unlike antibiotics, phages are designed (by nature, not man) to kill very specific “bad” bacterial strains. Phages that kill your bad bacterial strains won’t hurt your your beneficial strains at all, in fact the dead bad bacteria will greatly benefit your microbiome (more on that later). They certainly will not infect, or hurt, your human cells, that is impossible. This means your microbiome (and you) are safe; not only safe but your beneficial bacteria are greatly benefited by the lack of competition and adverse conditions created by those unwanted strains.

“The studies were conducted at the Hôpital des Enfants-Malades in Paris in 1919 (68) under the clinical supervision of Professor Victor-Henri Hutinel, the hospital’s Chief of Pediatrics. The phage preparation was ingested by d’Herelle, Hutinel, and several hospital interns in order to confirm its safety before administering it the next day to a 12-year-old boy with severe dysentery. The patient’s symptoms ceased after a single administration of d’Herelle’s antidysentery phage, and the boy fully recovered within a few days. The efficacy of the phage preparation was “confirmed” shortly afterwards, when three additional patients having bacterial dysentery and treated with one dose of the preparation started to recover within 24 h of treatment.” — PMID # PMC90351

History

Where have phages been? In nature phages are everywhere, and always have been. In medicine they were used in the 1920s and 1930s in Russia, Romania, and even the U.S.; this use pretty much ended when antibiotics were developed and marketed by the drug companies. Because of the “miracle” of antibiotics, funding for phage research dried up. People (and especially Doctors) were fascinated by drugs that could wipe out all bacteria, they didn’t want specificity, they wanted a drug that killed a wide spectrum of bacteria, at the time they thought all bacteria were “bad”. Doctors usually didn’t know what type of bacteria was causing someone to be sick, so antibiotics were the answer. Even today doctors are much more likely to prescribe antibiotics based on symptoms than on cultures, so doctors still like broad-spectrum antibiotics.

“Prior to the discovery and widespread use of antibiotics, it was suggested that bacterial infections could be prevented and/or treated by the administration of bacteriophages. Although the early clinical studies with bacteriophages were not vigorously pursued in the United States and Western Europe, phages continued to be utilized in the former Soviet Union and Eastern Europe.” – PMID # PMC90351

Due to the poor understanding of phages at the time, even when phages were used they were often used improperly; the wrong phage was applied to the disease (not the matching phage / bacteria combination), other medications were used that interfered with phages, killing the phages before they could do their job. These same issues also caused scientific studies to fail. In one such study patients receiving phages were also treated with lactoferrin and silver (DOI # 10.12968/jowc.2009.18.6.42801), the study concluded that adding phages did not improve healing. We now know this was because because phages are easily killed by these substances, and many other antiviral / antiseptics. Many subsequent studies have concluded phages do speed healing and you can expect to see many phage treatments coming out in years to come (many are going in to testing phases in the next year or two. Though I’ve seen no prescription trials in the works for gut issues other than c. difficile).

Doctors didn’t know that killing all the good bacteria in the gut was a very, very bad idea. So phages were out, and antibiotics were in.

What has changed since then? Not a whole lot, but in countries where pharmaceuticals aren’t in charge of healthcare there has been research on phages. We know we’re quickly losing effective antibiotics due to antibiotic resistance, so something needs to be done, and soon. With modern equipment and techniques phages can be isolated from the environment easier than ever before, and some are actually coming to market!

Safety

Are phages truly safe? Here is what the FDA says about phages:

“Bacteriophages (phages) are viruses that infect only bacteria and do not infect mammalian or plant cells. Phages are ubiquitous in the environment, and humans are routinely exposed to them at high levels through food and water without adverse effect.” — FDA.GOV

“Bacteriophages do not usually cross species or genus boundaries and thus, would not be expected to affect commensal bacteria in the gastrointestinal tract. Phages are the most abundant self-replicating units in the environment and are present in significant numbers in water, fermented foods such as sauerkraut and cheeses, and other foods including meats, poultry, and vegetables. Given their ubiquitous presence in foods, phages are routinely consumed at high levels and their prevalence in the human gastrointestinal tract is documented.” – FDA.GOV

“bacteriophages had no effect on normal microflora and did not aggravate dysbiotic disturbances. For this reason, bacteriophages may become one of alternative antimicrobial remedies, selectively affecting infective agents.” – PMID # 1882608

“The phage preparation was reported to be (i) efficacious in treating experimental infections of mice and (ii) nontoxic in mice and guinea pigs; i.e., gross and histological changes were not observed after intravenous (i.v.), intranasal, and intraperitoneal administration, even after a dose approximately 3,500-fold higher (estimated by body weight) than the human dose was given to mice during acute toxicity studies… From a clinical standpoint, phages appear to be innocuous. During the long history of using phages as therapeutic agents in Eastern Europe and the former Soviet Union (and, before the antibiotic era, in the United States), phages have been administered to humans (i) orally, in tablet or liquid formulations (105 to 1011 PFU/dose), (ii) rectally, (iii) locally (skin, eye, ear, nasal mucosa, etc.), in tampons, rinses, and creams, (iv) as aerosols or intrapleural injections, and (v) intravenously, albeit to a lesser extent than the first four methods, and there have been virtually no reports of serious complications associated with their use” – PMID # PMC90351

Method of Action

Here is where the real science fiction comes in, except it’s all real!

A regular virus infects living cells and forces them to do their bidding, basically creating a viral factory in each cell to create more viruses. When a virus attacks human cells our immune system detects them and tries to put a stop to it. With some diseases, most infected cells end up dying from the infection so it is important for the immune system to stop this quickly. Some viral infections, however, may cause little damage to the cell and may live commensally for years, or even for the life of the host (e.g. us).

A phage is a special type of virus that only infects bacteria, it does not have the ability to infect human or plant cells. Each phage species has a very narrow range of bacteria that it can infect. Thus, a phage supplement designed (by nature) to destroy certain bacterial strains will not (and cannot) damage the beneficial bacteria in our microbiome.

When a phage infects a bacterium it injects its genetic material into the bacterium. Lytic phages (the type we’re discussing here) take over the bacterium and force it to replicate this material to create new phages. Once this has been accomplished the phage will destroy, or lyse, the bacterium. This basically explodes the bacterium cell to release the new phages. These new phages need to find a new bacterium to infect (again, it must be the same strain), and thus the cycle continues. This process happens quite quickly, in most cases, hours.

With phage therapy, we’ve basically set loose very specific killing machines. Phages actively seek out and destroy only specific types of bacteria, leaving beneficial bacteria untouched and well fed (see below). When they run out of their matching bacteria, they die.

Benefits

Bacteriophages are currently available for the following bacterium, all of which have antibiotic resistant strains (which are still just as easy for phages to kill):

  • Staphylococcus spp.
  • Enterococcus spp.
  • Pseudomonas aeruginosa
  • Proteus mirabilis, Proteus vulgaris
  • Streptococcus spp.
  • Escherichia coli
  • Salmonella spp.
  • Shigella spp.
  • Klebsiella spp.

Not all of the bacteriophages listed above are commercially available, and few are being used in medicine in Western countries. There simply isn’t profit in it. Doctors are also very hesitant to use something that does not have the liability backing of a drug company. If someone dies because phages were used, rather than the “standard of care”, antibiotics, then the doctor gets sued, not the drug company (even though phages won’t kill anyone, people can still die from their original infection). But the biggest reason phages aren’t being used is probably because there is no big pharmaceutical company advertising and promoting phage therapy; for better or worse, it is all about money.

“The rates of success (marked to complete recovery in conjunction with negative cultures) ranged from 75 to 100% (92% overall) and were even higher (94%) with the 518 patients for whom antibiotic therapy was ineffective… Staphylococcus aureus phages were used to treat patients having purulent disease of the lungs and pleura… Overall, complete recovery was observed in 82% of the patients in the phage-treated group as opposed to 64% of the patients in the antibiotic-treated group.” – PMID # PMC90351

“These recent studies have confirmed that phages can be highly effective in treating many different types of bacterial infections. The lethality and specificity of phages for particular bacteria, the ability of phages to replicate within infected animal hosts, and the safety of phages make them efficacious antibacterial agents.” – PMID # 11909002

“Prophylactic (preventative) use of bacteriophages resembles that described for bacterial probiotics. In essence, phages administered orally can eliminate diarrheic pathogens like Salmonella spp., Clostridium difficile and E. coli. They can also—if designed to do so—modulate the gastrointestinal microbiota composition in a preferred way, bringing further benefits for the host” – PMID # PMC5243869

“The results of this study have clearly shown the lytic activity of commercial bacteriophage cocktails on E. coli and K. pneumonia strains isolated from patients suffering from UTIs… In view of the high prevalence of UTIs, bacteriophages, as natural and self-amplifying antibacterial “drugs,” might offer a non-systemic effective therapeutic option” – PMID # PMC4826877

  • When phages remove bad bacteria from their environment (in this case the gut) it makes room for beneficial bacteria. The more that beneficial bacteria replace bad bacteria, the harder it is for the bad bacteria to return.
  • When phages lyse (explode) bad bacteria their cells become food for good bacteria.
  • Phage therapy can start working in just a few hours, not days or weeks, which is the case with antibiotics. However, treatment may have to be kept up for several months to completely eradicate an infection, rather than just control it.
  • Bacteriophages are very specific, targeting only one or a few strains of bacteria. Antibiotics, on the other hand, have more wide-ranging effect, killing both harmful bacteria and beneficial bacteria.
  • Works with most strains of good bacteria to boost their numbers throughout the gut.
  • Stimulates the colon to maintain a normal microflora
  • Found to be safe, with few if any side effects, in many independent studies, even when taken at many times the effective dose.

Future

I’m seeing a lot of interest in phage and “phage cocktails”. Right now there are several drug companies investigating phages and applying to the FDA to begin human studies. There is also interest in using phages to prevent meat spoilage at grocery stores and our supply chain.

There are currently a few phage products available and currently coming to market. Now that costs of development have come down I think we will start seeing far more new strains becoming available (remember, they’re GRAS so costly FDA approval is not required). The products will be inexpensive as they will not be patentable, but aspirin is not patentable and plenty of companies are making it. So I think the future of phage therapy is a bright one. The main hurtle is that they will not be allowed to be marketed and used as a “drug” unless they go through the multi-billion dollar FDA approval process. They can be used OTC as a “food supplement” or “prebiotic”.

“It’s the only medicine that grows” – Ryland Young, head of the Center for Phage Technology at Texas A&M University

A news story came out in May 2017 about a couple on vacation to Egypt in early 2016. The husband, Tom, became gravely ill and antibiotics were not helping. Turned out he had contracted a bacterial infection called Acinetobacter baumannii, it first infected his gut, but quickly spread to his blood and lungs. He was airlifted first to Frankfurt Germany and then to San Diego, where he was in an ICU for months and very near death most of that time. His wife, Steffanie Strathdee, is the director of UC San Diego’s Global Health Institute, and one of the world’s experts on how HIV spreads. She began a quest to find a last resort treatment for her husband, Tom. It’s an excellent story of love, courage, and persistence. In the end she worked with the U.S. Navy and Ryland Young of Texas A&M to isolate phages that can attack Acinetobacter baumannii. They went on a phage hunt collecting samples from sewage plants in Texas and located about 100 that might be able to help Tom. Getting FDA approval for a “compassionate” use of phages was no easy task, but because of Steffanie’s position and persistence, that approval was obtained. It took nine months of treatment but Tom was able to leave the hospital and go home, all due to one of the first uses of phages to treat a dying patient in decades!

We can only hope that the FDA will loosen the regulations around natural treatments and allow them to be used with the very costly FDA approval process. If they’re safe enough to use as a “supplement” they should be safe enough to save a dying, or very sick person under a doctor’s care.

Today

Other than treatments at specialized clinics in Romania are there any uses of Phages that are available now?

Yes, in fact there are. There is a phage complex being used as a “Prebiotic” in a supplement intended to promote gut health.

Since prebiotics are not used to treat disease and the phages are considered GRAS, they do not FDA approval as a drug if they qualify as a nutritional supplement or prebiotic. Here is how the FDA defines a prebiotic, “Prebiotics have been defined as nondigestible food ingredients that beneficially affect the host by selectively stimulating the growth and/or activity of one or a limited number of bacteria in the colon”. When phages kill bad bacteria the good bacteria consume the dead cells; several studies have shown that beneficial bacteria greatly benefit from the death of these competing bacteria.

One product you may want to investigate is “Phage Complete” by The Gut Protocol LLC.  This location includes more information and research studies on phages for gut health.

These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

 

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