Modulation of gut microbiota is emerging as a potential strategy to alleviate various gastrointestinal disorders. Two new papers report bacterial-based interventions that prevent virulent Vibrio cholerae infection in animal models. Hubbard et al. engineered a live, orally administered cholera vaccine candidate, HaitiV, by introducing nine genetic modifications into the Haitian outbreak strain of V. cholerae to delete known factors associated with virulence, reactogenicity and drug resistance, and to prevent reversion. Administration of HaitiV to an infant rabbit model of cholera protected against lethal doses of virulent V. cholerae strains given 24 hours later. Killed HaitiV did not confer such resistance, suggesting that the rapid protection may result from a probiotic effect. Meanwhile, Mao et al. demonstrate that oral administration of Lactococcus lactis — which is used as a probiotic to promote general health — to infant mice at the same time or 5 hours before V. cholerae exposure reduced V. cholerae burden and substantially increased survival through the production of lactic acid. The authors bioengineered L. lactis to produce L. lactis CSL that detects quorum-sensing signals of V. cholerae in the gut and triggers expression of an enzymatic reporter, which could be detected in faecal samples of mice to diagnose cholera.