Are phage bacteria slayers the new antibiotics?
It doesn’t seem right to think of a virus as a friend — especially given the adversarial relationship between viruses and our immune system. But now comes research that blows a hole in the idea that viruses are always the bad guys.
They’re called phages (short for bacteriophage), viruses that specifically infect and often kill harmful bacteria but do not injure humans. Smaller than bacteria, phages are ubiquitous viruses found wherever bacteria exist. There are, for example, an estimated 1031 — ten million trillion trillion — phages on Earth, more than every other organism, including bacteria, put together. The average teaspoon of seawater, for instance, contains five times as many phages as there are people in Rio de Janeiro.
In natural ecosystems, phages are powerful regulators of bacterial populations. Phages also invade the human body in such massive numbers that they are the most numerous group in the human virome, the collection of viruses in and on the human body.
Phages colonize all niches of the body, including the skin, oral cavity, lungs, gut, and urinary tract. They enter through food and water, through the air we breathe and even just rubbing up against things.
An Australian study in November found that people absorb up to 30 billion phages every day through their intestines, many of which shadow and target harmful microbes in our gut microbiome. According to this study and others, the sea of phages within our bodies – a “phageome” – might very well be influencing our physiology, most likely by regulating our immune systems.
Other research published in the National Center for Biotechnology Information (NCBI) concludes that metagenomic studies of microbiota at various tissue sites have revealed that many of the viruses associated with healthy human tissues are phages. And that phages likely have a profound impact on the composition and functional properties of the bacterial microbiota, which in turn could shape development and function of the immune system. This most likely is accomplished through the predation of susceptible bacterial strains.
It shouldn’t be surprising that researchers now believe phages impact our immune systems. Studies show that our gastrointestinal tract is loaded with about 3 pounds worth of both bacteria (beneficial and harmful) and viruses (both beneficial and harmful). Collectively these 100 trillion microbes are known as the microbiome.
It’s now known that microbiome bacteria produce chemicals called neurotransmitters (such as serotonin) that significantly impact the central nervous system – especially our mental well-being.
“In the human gastrointestinal tract, good bacteria aid in digestion and helps produce vitamins,” says Dr. Jerry Kanellos, chief operating officer for Australian biotech company Immuron. “It also helps with immunity, making the body less hospitable to bad bacteria and other harmful pathogens.”
Essentially, the immune system is the main link between our gut microbiota and its influence on our health and disease.
“The bacteria in your gut communicate directly with the immune system and the brain,” says microbiology professor Holly Ahern. “Certain members of the gut microbiota are known to ‘train’ the immune system in terms of what to attack and what to leave alone.”
Dr. Amesh Adalja is a board-certified infectious disease physician and Senior Scholar at the Johns Hopkins Center for Health Security. Adalja believes the gut microbiome plays an “essential role” in our immune function.
“Disruptions to the gut microbiome have cascading effects to the immune system that can be deleterious,” says Adalja.
Primal health coach Susan Hoff characterizes the gut microbiome as “incredibly complex.” She believes a strong immune system requires a microbiome “as balanced as possible,” which means having the right amount of good bacteria while “populating more rare bacteria and decreasing levels of bad bacteria.”
In other words, achieving homeostasis, something phages help with by “taking out” specific strains of bad bacteria.
Vampire Slayers And Body Snatchers
Phages are different from other viruses because they infect bacteria. In fact their full name, “bacteriophage,” literally means “bacteria eater.” But like all viruses, phages must infect a host cell in order to reproduce. The steps that make up the infection process are collectively called the phage life cycle and are either lytic or lysogenic.
The lytic life cycle is somewhat reminiscent of how vampires vaporize when they’re killed. It could also be looked at as an exploding water balloon. The assassin phage injects its double-stranded DNA genome into the cytoplasm of the targeted bacterium. Eventually the doomed bacterium takes on water and bursts in a process known as lysis. The evanescing bacterium dies but not before releasing hundreds of new phages, which can find and infect other host cells nearby.
The lysogenic method of phage reproduction has a body snatching feel about it. As with the lytic approach, the attacking phage injects its DNA into the host. But instead of killing the hapless bacterium, the phage uses it by combining its DNA with a particular region of the bacterial chromosome. This causes the phage DNA to be integrated into the chromosome, which creates an integrated phage DNA, called a prophage. Then, each time the host cell divides, the prophage DNA is copied along with the host DNA. In this way, the phage virus reproduces every time the bacterium does.
Is This Just A Phage We’re Going Through?
While the phage/immune system research provides new insights into how prey and predator microbes coexist in the same microbiome, are there really any practical applications here?
The answer is absolutely.
Dr. Kenny Fine is an internationally renowned intestinal researcher, professor and founder of the nonprofit Intestinal Health Institute. According to Fine, researchers are looking for ways to use phages as a way of manipulating the bacterial flora in our colon for positive therapeutic gain.
“It is possible that the concept of probiotics in the near future will incorporate both bacteria and phages,” says Fine.
Probiotics are supplements that introduce friendly bacteria in the digestive tract to promote healthy gut function. The addition of phages to a probiotic mix could be beneficial, especially phages that hunt down specific harmful bacteria.
A number of scientists have also been looking into ways to use phages to clean hospitals or industrial surfaces, since they can destroy undesirable bacteria like disinfectants do.
It might also be possible to include phages in foods as a biotech preservative. The phages would wait in the food until some harmful bacteria contaminated it. This would trigger the phages to kill the bacteria.
But the overwhelming interest among researchers is in the area of phage therapy, the application of bacteria-specific viruses (phages) to combat uncontrolled and undesired bacteria such as those associated with infectious disease. As our time with antibiotics is running out due to superbug resistance, some advocates believe phages are the best replacement for fighting bacterial diseases.
In fact, phages as antibiotics have already been used to save lives in non-Food and Drug Administration (FDA) approved experimental treatments, according to a Harvard University report.
One such case involved a man named Tom Patterson who was infected by a multidrug-resistant strain of Acinetobacter baumannii bacteria while on vacation in Egypt. He was flown back to California and treated with antibiotics for more than 100 days, but Patterson did not improve and then fell into a coma. As a last resort, he was saved by a cocktail of a specific variety of purified phage discovered in Texas sewage.
But even if superbugs from overuse of antibiotics had never developed, phages might still be a better choice since they only infect a few strains of a bacterial species versus x, y and z. Consider also that antibiotics rip apart our gut microbiome (and immunity) by destroying good and bad bacteria.
Really, What Do We Know?
In a way, the enigma of the night sky is similar to the unfathomable mystery of the microbial world within us. Astronomers tell us there are something like a trillion galaxies each composed of 100 thousand million stars. Microbiologists say we have between 50 to 70 trillion gut microbes – more than all the stars in the Milky Way galaxy.
As reported by the Human Microbiome Project (HMP), we are mostly microbes. Our human genes are outnumbered at least 150 to 1 by the genes of our microbes. We are completely dominated by the microbes in and on our bodies – so much so that it is more accurate to imagine ourselves as clouds of microbes with a few human cells along for the ride.
Another way of putting it, we aren’t really who we thought we were. And as far as our immune system, it also isn’t what we thought it was.
“Much more is unknown than is known on this subject,” says Dr. RJ Oenbrink DO of Appalachian Wellness. “Most practicing physicians don’t believe yet in the concept of leaky gut much less all of the problems that stem from that condition.”
Or in the words of microbiologist Ahern:
“I think it is safe to say that science overall only understands a fraction of what makes human physiology work. Especially now in the age of the microbiome, where we’re realizing that human physiology is partly based on us but also based on the physiology of our microbial inhabitants.”
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