A new topic – and vocabulary word – for The Biome Buzz: proteobiotics. You know that I am very enthused about research into using bacteriophages (viruses native to the human biome which target specific bacteria) as an old/new therapy to deal with infection. (You can read more about that here, as just one example.) However, I am now equally mesmerized with proteobiotics, which is defined as the metabolites of specific probiotic bacteria to alter the course of infection by pathogenic species.
I have been slowly making my way through bucket loads of papers I’ve saved on my computer, and over the weekend, finally got to one published last February on using proteobiotics as antimicrobial therapy.[i] The paper starts with a short synopsis of the history of antibacterial treatments, including this astounding fact: within 1 year of the invention of the first form of penicillin (G), “…the development of resistant strains capable of inactivating the drug emerged…” That is, it took only a year for drug-resistant bacteria to develop. This was not a one-off: the same happened when other new antibiotics were developed including tetracyclines, aminoglycodies, and cephalosporins: “…bacterial resistance against these antibiotics emerged within the same year that the antibiotic was introduced.”
It’s not a wonder then that in the USA alone, 2.8 million people are infected with antibiotic resistant bacteria every year, resulting in 38,000 deaths.
The paper describes some of what we know about how metabolites from our own gut bacteria help keep pathogens in check. Proteobiotics interrupt communication between pathogens and our cells, preventing what is known as “virulence”: the pathogen’s ability to cause an infection in the host. There are several known mechanisms of action, including one I’ll focus on for today’s post: quorum sensing. This is the ability of bacteria to recognize host cells’ signals that alert the bacteria that they are at the site of infection, i.e. there are chemical signals emitted by infected cells, which bacteria can sense. Pathogens are attracted to that area, increasing the strength of the infection. Proteobiotics can “…specifically interfere with the ability of the bacteria to recognize host signals that alert the bacteria that they are at the site of infection…” thereby reducing virulence. And because this does not directly kill pathogens, there is no potential for the development of antibiotic resistance.
The authors describe several experiments using proteobiotics to inhibit infection. Proteobiotics from Lactobacillus acidophilus have successfully suppressed the virulence of a pathogenic E.coli both in vitro and in animal models by suppressing quorum sensing in the bacteria. Two groups of mice were infected with a very pathogenic E.coli species. Those animals also given the proteobiotics fared far better: the mice had significantly less of the pathogen after 5 days, as opposed to the untreated animals who had far more of it. This latter group showed signs of physical deterioration too whereas the treated mice remained in “acceptable” health.
Proteobiotics from Lactobacillus acidophilus have also been shown to control the virulence of Clostridium difficile infection, which is particularly exciting considering how incredibly difficult this is to treat. (You can read more about it here.) This bacterium excretes toxins, which is its main “virulence factor.” In vitro, the proteobiotics down-regulated the toxin genes of the C.difficile, and experiments have confirmed that these bioactive molecules from L.acidophilus, “…have the ability to reduce toxin production.” Further experimentation found that the proteobiotics can also suppress quorum sensing in C.difficile.
Recent research has also shown that proteobiotics from Lactobacillus plantarium have anti-proliferative effect on cancer cells (i.e. stop them from reproducing), as well as inducing apoptosis (cell death) in malignant cells, while sparing normal cells. Holy cow, right?!
It turns out, unfortunately, that the only commercially available product with proteobiotics is formulated for pigs and dogs. The products are produced by MicroSintesis, Inc. The products apparently work great but – they are not available for people. Figures.
The conclusion – you guessed it: much more research is needed. But at least the outlook seems bright.