摘要：SummaryClostridioides difficile (C. diff)is the leading cause of antibiotic-associated colitis. Here, we report that lemon exosome-like nanoparticles (LELNs) manipulated probiotics to inhibitC. diffinfection (CDI). LELN-manipulatedLactobacillus rhamnosusGG (LGG) andStreptococcus thermophilusST-21 (STH) (LELN-LS) decrease CDI mortality via an LELN-mediated increase in bile resistance and gut survivability. LELN-LS treatment increases the AhR ligands indole-3-lactic acid (I3LA) and indole-3-carboxaldehyde (I3Ald), leading to induction of IL-22, and increases lactic acid leading to a decrease ofC. difffecal shedding by inhibitingC. diffgrowth and indole biosynthesis. A synergistic effect between STH and LGG was identified. The STH metabolites inhibit gluconeogenesis of LGG and allow fructose-1,6-bisphosphate (FBP) to accumulate in LGG; accumulated FBP then activates lactate dehydrogenase of LGG (LGG-LDH) and enhances production of lactic acid and the AhR ligand. Our findings provide a new strategy for CDI prevention and treatment with a new type of prebiotics.Graphical AbstractDisplay OmittedHighlights•LELNs-manipulated probiotics protect mice fromC. diffinfection•LELNs manipulation modulates gut metabolomics composition•Cross talk between LGG and STH enhances production of lactic acid and AhR ligandsNanoparticles; Microbial Metabolism; Dairy Microbiology
