An international team of researchers in Zurich and Oxford have identified a promising strategy to combat harmful bacteria in the gut using a combination of oral vaccines and microbiome-based competition. The approach could help eliminate antibiotic-resistant pathogens and reduce dependence on traditional antibiotics.
Led by Emma Slack, PhD, a professor at ETH Zurich and the University of Oxford’s Sir William Dunn School of Pathology, and Médéric Diard, PhD, a professor at the University of Basel, the team demonstrates how pairing immunization with beneficial bacteria can eliminate intestinal infections. Their findings were published in Science in a paper titled, “Vaccine-enhanced competition permits rational bacterial strain replacement in the gut.”
Using a concept rooted in microbial ecology, the team focused on replacing harmful bacteria with harmless strains that occupy the same niche in the intestine. “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 mouse models, the researchers tested a two-pronged strategy: oral vaccination followed by administration of competitor bacteria. For prophylactic treatment, they genetically engineered a Salmonella strain to outcompete nontyphoidal Salmonella strains. For therapeutic treatment, they selected a mixture of three naturally occurring E. coli strains to displace established E. coli infections.
“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,” Slack said.
Vaccination alone provided partial protection, and the introduction of competitor bacteria on their own also had a partial protective effect. Combining treatments resulted in a near-complete clearance of the pathogens from the intestine. “Both intact adaptive immunity and metabolic niche competition are necessary for efficient vaccine-enhanced competition,” the authors wrote.
With growing concerns over antibiotic resistance, there is an urgent need for alternatives to traditional antibiotics. The new method may provide a path forward, especially for immunocompromised patients at risk of severe infections, and may help pave the way for a reduction in the use of antibiotics.
In the long term, the goal is to create a simple treatment option—such as a capsule—that combines a targeted vaccine with specific competitor bacteria. While such applications are still several steps away, this study lays the foundation for further translational research into clinically relevant pathogens and human gut ecology.
“Our findings imply that mucosal antibodies have evolved to work in the context of gut microbial ecology by influencing the outcome of competition,” the researchers wrote. “This has broad implications for the elimination of pathogenic and antibiotic-resistant bacterial reservoirs and for rational microbiota engineering.”