When it comes to the human body’s trillions of microbial inhabitants, sorting the good from the bad is critical. Antibiotics are powerful weapons for obliterating nasty, disease-causing germs, but they can also take out microbial chums as collateral damage. The loss of those invisible allies can have long-term, cascading health effects, including opening opportunities for invasions by enemy microbes, such as Clostridium difficile and Vancomycin-resistant Enterococcus faecium (VRE).

Fixing such a culled, out-of-whack microbial community in the human body—a condition called dysbiosis—is hard. Scientists still don’t have a firm hold on the recipe for a “healthy” microbiome, let alone know how to mend one that appears imbalanced. The closest researchers have come to such a feat is with the use of fecal transplants to restore gut communities—essentially a wholesale replacement of a wrecked microbial community with a functional one.

But now researchers may be on to a way to prevent dysbiosis in the first place.

By duping the immune system of mice into fighting off a nonexistent virus, researchers were able to protect the rodents’ gut microbiomes by blocking VRE from moving in after an antibiotic treatment. The finding, published Wednesday in Science Translational Medicine, hints at future combination drug treatments with antibiotics that could dodge dysbiosis and the need for fecal transplants and other microbiome restorations.

The researchers, led by immunologists at the Memorial Sloan Kettering Cancer Center, got started on the idea of harnessing a viral decoy knowing that such germs normally manipulate and prune the gut microbiome. The community of viruses that bustle in human guts—called the virome or microvirome—trigger anti-microbial immune responses that can put the microbial communities on lock down, preventing new microbes from colonizing.

Such a state of “colonization resistance” in the gut could thwart harmful germs from moving in, particularly when the microbiome is imbalanced and vulnerable after antibiotic treatments, the researchers hypothesized—and they found they were right.

As in humans, antibiotics mangle the gut microbe communities in mice. In a study from the 1960s, scientists reported that a single dose of an antibiotic left mice nearly a million-fold more susceptible to infection by a disease-causing Salmonella. Likewise, when the researchers of the new study gave mice an antibiotic and then exposed them to VRE, the infectious germ quickly colonized and took over. Such dense populations of VRE in human guts cause severe infections that can break through to the bloodstream and cause sepsis—a dangerous, full-body immune response to an infection. And, because VRE is resistant to some drugs, it’s difficult to treat.

When the researchers repeated the experiment with the antibiotic-treated mice and VRE—but this time also infecting them with the mouse version of norovirus—VRE colonization was stymied.

Still, infecting patients with a disease-causing virus is "clinically impractical,” the authors acknowledged. Instead, they looked for a molecular component of the virus that could work as a drug with the same overall effect. They found it in a molecule called resiquimod (R848), which is a previously created, synthetic chemical that mimics virus-derived, single-stranded RNA and sparks the same immune responses.

In subsequent tests in antibiotic-treated mice, R848 was even better at thwarting VRE infections than the virus. And, the researchers found, it triggered the same “colonization resistant” immune responses, which, notably, have clear analogues to responses in the human immune system.

While the animal study data is promising, there’s a long way to a treatment in humans, the authors caution. A particular concern is that the virus-mimicking particles could spur overblown immune responses that would do more harm than good. Still, the authors conclude, the data suggests that such drugs may one day "limit infection by intestinal pathogens in antibiotic-exposed, susceptible individuals.”

Science Translational Medicine, 2015. DOI: 10.1126/scitranslmed.aad6663 (About DOIs).