Researchers combined a vaccine and a probiotic supplement to tend the microbial garden inside the intestines of mice, protecting the rodents from harmful infections or treating them if they’ve already caught a nasty bug as scientists continue to seek a future alternative to antibiotics.
The technique, which the researchers call vaccine-enhanced competition, uses an oral vaccine to wipe out the bad bacteria and then seeds the gut with beneficial microbes to take their place. The researchers, led by immunologist Emma Slack, Ph.D., of ETH Zurich in Switzerland, published their results in Science on April 3.
Because the technique can remove bacteria without antibiotics, the researchers hope the vaccine-probiotic combo can one day reduce antibiotic use and prevent the spread of antibiotic-resistant bacteria.
“Although we can decimate pathogenic bacteria with a vaccine, we need harmless microorganisms to fill the resulting niche in the intestinal ecosystem in order to achieve long-term success,” Slack said in an April 3 release about the results. “It’s like gardening. If you want to avoid weeds in an area of the garden, you have to plant other plants there after weeding. If you leave the soil empty, the weeds will just grow back.”
To see whether the technique could be used to prevent a Salmonella gut infection, the researchers first genetically engineered a strain of Salmonella bacteria to be harmless. They then gave mice an oral vaccine, consisting of inactivated pathogenic Salmonella cells, to trigger the immune system to recognize an infection. Alongside the vaccine, mice received the harmless Salmonella strain as a probiotic.
When treated with both the vaccine and the harmless bacteria, mice exposed to pathogenic Salmonella days later didn’t develop infections. Control mice, which didn’t receive either the vaccine or the probiotic, came down with a Salmonella infection in their guts. The vaccine and the probiotic alone could both help suppress infection, but not as well as they did as a combo.
A similar combo treatment, consisting of an oral vaccine and three harmless E. coli strains, was able to clear a pathogenic E. coli infection from mice.
“We have identified a mechanism to prevent Salmonella colonization and achieve E. coli strain replacement in the gut,” the researchers wrote in their paper. “These results lay the foundation for targeted treatments for bacterial infections in mammals, promising advancements in medical science.”
The strains of Salmonella and E. coli used in the study are not the same as the ones that infect humans. Slack and her team next hope to apply the technique to mice infected with the same strains of bacteria that infect humans and eventually progress to studies in infected humans themselves, according to the release.