Trillions of microbes live in and on our bodies. Scientists are trying to use this so-called microbiome to ward off diseases. They have altered the genomes of bacteria that live on the skin, creating microbes that can prevent or even treat cancer. This seems to work for mice. And with humans?
“I think this is really a big breakthrough,” says Julie Segre, a geneticist and skin biologist at the National Human Genome Research Institute in Bethesda, Maryland, who was not involved with the research. The idea of harnessing microbes to treat cancer and potentially other diseases is “a very exciting new avenue for the microbiome,” she says.
Our coexistence with microbes
Most research on the microbiome has focused on the trillions of microbes that live in our guts. But our skin is also home to a large number of microbial ecosystems. The ecosystem in the armpit can look very different than that on the eyelids. It’s still unclear exactly what these microbes do, but they appear to feed on human secretions and may be able to produce some useful secretions of their own to protect us from infection.
The microbiome seems to influence how our immune system works. Research suggests that microbes that live in and on our bodies can increase or decrease the immune response to something that could potentially harm us, whether it’s an infection, a tumor or something more benign.
Even the mere introduction of a microbe into an animal’s skin can trigger an immune response — albeit one that doesn’t produce the usual signs of infection, such as pain, fever, or nausea. That’s a little surprising, says Stanford University microbiologist Michael Fischbach, because these microbes aren’t usually harmful: “They’re our friends.” For example, putting a microbe on the skin of a mouse can have a similar effect as vaccinating the same mouse.
Modified Microbes
Fischbach and his colleagues wondered whether they could use this effect to specifically influence the immune response. Their results were recently published in the journal “Science”.
The team began their investigation by choosing a microbe commonly found on human skin: Staphylococcus epidermidis. The bacterium is believed to be a part of the human microbiome that does not normally cause disease. The microbes the researchers used were originally collected from behind the ear of a human volunteer, Fischbach explains.
The researchers modified these microbes by inserting a new gene into them. The gene encodes a protein found on the surface of some cancer cells. If the immune system creates cells that recognize the microbe, those cells will also recognize tumors. The team then applied these ‘designer bacteria’ to mice by wiping them over the animals’ heads with a cotton swab. A comparison group were normal, unaltered samples of S. epidermidis smeared on the head.
In both cases, the microbes quickly colonized the mice’s skin, Fischbach says. At the same time, the mice were injected with skin cancer cells. These cells were derived from other mice that had cancer, so they carried the target protein on their cell surface.
target of the tumor
In the days and weeks that followed, these cancer cells grew into tumors in the mice that received the regular microbe. However, in the mice given the engineered microbe, the progression of the cancer slowed significantly. “You could see these huge tumors growing on the side of the mice that had the normal one S. epidermidis But nothing could be seen in the mice given the modified microbes. The scientist points out that this particular type of cancer in mice is known to be aggressive and difficult to treat.
“We were surprised by the extent of the reaction,” says Fischbach. “It’s surprisingly strong considering how mild the treatment is.” The treatment also worked in mice that had previously developed tumors. The tumors appeared to shrink in the animals coated with the engineered microbes. Fischbach and his colleagues still have a lot of work to do before they can test the artificial microbes on humans. First, they need to find a good candidate microbe. It is unclear whether S. epidermidis triggers the same immune response in humans as in mice. Another microbe may work better.
hope of human experimentation
In addition, the researchers have to select a suitable cancer protein as a target. This has proven to be a challenge in developing anti-cancer mRNA vaccines, which also rely on eliciting an immune response to a cancer protein. Unlike many infectious diseases, there is often no obvious candidate.
As soon as the researchers have found out which microbe they will change and how, they want to test their safety using animal experiments. Michael Fischbach hopes to be able to carry out experiments with designer microbes on people with cancer in the next few years. Although the team’s focus is on cancer, the modified bacteria could also be used to treat other diseases and allergies, write Elaine Fuchs of Rockefeller University in New York and her colleagues in an accompanying comment in Science magazine. Further exploration of the use of modified microbes “could pave the way to safer, more effective and widely applicable therapeutics,” the team writes.
“What excites us is the idea that you could just rub that behind someone’s ear and walk away,” says Fischbach. “And then, ten days later, you could see a strong immune response that basically lasts indefinitely.”
(jl)