We have heard of friendly gut bacteria that help us digest food and are thought to be essential for gut development, but now, in a new breakthrough study, scientists in the US suggest we also carry friendly viruses that shield us from infection by dangerous bacteria like E. coli.
First author Jeremy Barr, a biology post-doctoral Fellow at San Diego State University, and colleagues, write about this previously undocumented “immune system” in a paper published online in the Proceedings of the National Academy of Sciences this week.
The researchers believe their discovery could change the way we treat a number of diseases.
Nasty bugs cause infection by penetrating surfaces of the body that are exposed to the environment, such the lungs which take in air and the guts which take in food.
That is why these exposed surfaces, in all animals, from corals to fish to humans, have protective layers of mucus that serve as a defence against infection, and are home for beneficial microbes, including fungi, bacteria and viruses.
Recently, scientists revealed just how extensive these microbial populations that live inside us are, and how at 3.3 million, gut flora genes vastly outnumber the 23,000 genes in the human genome.
Now Barr and colleagues have discovered that mucus also contains a population of viruses called bacteriophages that actively protect their hosts from dangerous bacteria by destroying them.
But they don’t do this for nothing, because in return, they are exposed to a continuous supply of microbes to feast on.
In a report of the study by Nature NEWS, Rotem Sorek, a microbial geneticist at the Weizmann Institute of Science in Israel, describes this relationship between virus and animal as a “unique form of symbiosis”.
For this latest study, Barr and colleagues sampled mucus from a variety of animals, ranging from a sea anemone to a mouse to a human, and found bacteriophages sticking to the mucus layer of all of them.
They put bacteriophages on a layer of mucus-producing tissue and saw how they formed bonds with sugars in the mucus, which helped them stick to the surface.
In further experiments they presented the mucus cells with E. coli bacteria and found the bacteriophages in the mucus attacked and killed the bacteria in the mucus, behaving like an anti-microbial barrier that protects hosts from infections.
They then confirmed their findings by carrying out the same experiments with non-mucus-producing cells. They challenged them with both bacteriophage and E. coli and found the samples with no mucus had three times more cell death.
In a statement, Barr refers to the discovery as a new kind of immune system:
“Taking previous research into consideration, we are able to propose the Bacteriophage Adherence to Mucus — or BAM — is a new model of immunity, which emphasizes the important role bacteriophage play in protecting the body from invading pathogens”.
Frederic Bushman, a microbiologist from the University of Pennsylvania calls the study “groundbreaking”. He says in the Nature NEWS report that “the idea that phage can be viewed as part of the innate immune system is original and exciting”.
Barr says the research could be applied to any mucus surface.
“We envision BAM influencing the prevention and treatment of mucosal infections seen in the gut and lungs, having applications for phage therapy and even directly interacting with the human immune system,” he adds.
Another interesting feature of this study is not only that bacteriophages can be viewed as a new kind of immune system, but that they are “not host-derived” but recruited from the environment to live in mutually beneficial partnership, in symbiosis, with their hosts.
Senior study author Forest Rohwer, a microbial ecologist at San Diego State, who has been studying mucus from many different animal species for some time, had noticed that mucus contains significantly more bacteriophages than mucus-free areas.
He and his colleagues became curious: how was it, for example, that saliva, which is right next to the gums, contains about 5 bacteriophages to every bacterial cell, but on the mucus surrounding the gum itself, this ratio is more like 40 to 1?
Barr says in a report on the study in Science NOW, this made them ask the question:
“What are these phages doing? Are they protecting the host?”
With their study they showed once recruited from environment, the bacteriophage naturally sticks to the various mucus layers in the body including the mouth and gut. It then starts protecting its host, accumulating and attacking bacteria on its own.
But Barr believes these viruses even go a stage further. He says some bacteriophages don’t kill bacteria, they genetically modify them (by inserting their genetic material into the microbe’s genome) to protect them against other phages.
He suggests this might be how mucus-borne bacteriophages actively protect host-friendly bacteria, and destroy the harmful ones.
There are numerous types of disease, such as inflammatory bowel disease (IBD), which includes Crohn’s disease and ulcerative colitis, that are caused by a breakdown in the mucus lining of the gut. The microbe ecosystems in the guts of patients with IBD have a different mix of dominant species compared to healthy individuals.
This “novel take on the whole microbiome-host relationship”, suggests “a failure in phage-based immunity” could be an important clue about what links these diseases, says Michael McGuckin, a mucosal biologist from Mater Research in Australia, in the Science NOW report of the study.
Barr suggests this symbiotic relationship between animal and bacteriophage has been going on ever since mucus was first produced. The BAM model he and his colleagues propose, suggests that “mucosal surfaces and phage coevolve to maintain phage adherence”.
He expects the discovery will “have a significant impact across numerous fields”. The team now wants to explore implications for human health.
For instance, Barr thinks it may be possible to line a person’s gut with bacteriophages that target specific disease-causing bacteria.
The National Institutes of Health helped to fund the study.
In 2011, in an astonishing study published in Nature, researchers in Germany described finding evidence that multiple sclerosis (MS) is triggered by friendly gut bacteria.
Written by Catharine Paddock PhD