Vaccine-enhanced competition permits rational bacterial strain replacement in the gut

• DOI: 10.1126/science.adp5011
• Publication Date: 2025-04-04T04:30:56Z
• Authors: Verena Lentsch; Aurore Woller; Andrea Rocker; Selma Aslani; Claudia Moresi; Niina Ruoho; Louise Larsson; Stefan A. Fattinger; Nicolas Wenner; Elisa Cappio Bara...; Wolf-Dietrich Hardt; Claude Loverdo; Médéric Diard; Emma Slack

Colonization of the intestinal lumen precedes invasive infection for a wide range of enteropathogenic and opportunistic pathogenic bacteria. We show that combining oral vaccination with engineered or selected niche-competitor strains permits pathogen exclusion and strain replacement in the mouse gut lumen. This approach can be applied either prophylactically to prevent invasion of nontyphoidal Salmonella strains, or therapeutically to displace an established Escherichia coli. Both intact adaptive immunity and metabolic niche competition are necessary for efficient vaccine-enhanced competition. Our findings imply that mucosal antibodies have evolved to work in the context of gut microbial ecology by influencing the outcome of competition. This has broad implications for the elimination of pathogenic and antibiotic-resistant bacterial reservoirs and for rational microbiota engineering.