Lentsch Verena, Woller Aurore, Rocker Andrea, Aslani Selma, Moresi Claudia, Ruoho Niina, Larsson Louise, Fattinger Stefan A, Wenner Nicolas, Barazzone Elisa Cappio, Hardt Wolf-Dietrich, Loverdo Claude, Diard Médéric, Slack Emma
Institute for Food, Nutrition and Health, ETH Zurich, Zurich, Switzerland.
Medical Research Council (MRC) Translational Immunology Discovery Unit, MRC Weatherall Institute of Molecular Medicine (WIMM), John Radcliffe Hospital, University of Oxford, Oxford, UK.
Science. 2025 Apr 4;388(6742):74-81. doi: 10.1126/science.adp5011. Epub 2025 Apr 3.
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 strains, or therapeutically to displace an established 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.
对于多种肠道致病细菌和机会致病细菌而言，肠腔定植先于侵袭性感染。我们发现，将口服疫苗与经过工程改造或筛选的生态位竞争菌株相结合，可在小鼠肠腔中实现病原体排除和菌株替代。这种方法既可以预防性应用，以防止非伤寒菌株的侵袭，也可以治疗性应用，以取代已定植的菌株。完整的适应性免疫和代谢生态位竞争对于有效的疫苗增强竞争都是必要的。我们的研究结果表明，黏膜抗体已进化为通过影响竞争结果在肠道微生物生态环境中发挥作用。这对于消除致病性和抗生素抗性细菌库以及合理的微生物群工程具有广泛的意义。
