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Lemon Exosome-like Nanoparticles-Manipulated Probiotics Protect Mice from C. diff Infection

ABSTRACT: Summary Clostridioides difficile (C. diff) is the leading cause of antibiotic-associated colitis. Here, we report that lemon exosome-like nanoparticles (LELNs) manipulated probiotics to inhibit C. diff infection (CDI). LELN-manipulated Lactobacillus rhamnosus GG (LGG) and Streptococcus thermophilus ST-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 of C. diff fecal shedding by inhibiting C. diff growth 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 Abstract Highlights • LELNs-manipulated probiotics protect mice from C. diff infection• LELNs manipulation modulates gut metabolomics composition• Cross talk between LGG and STH enhances production of lactic acid and AhR ligands Nanoparticles; Microbial Metabolism; Dairy Microbiology

SUBMITTER: Lei C

PROVIDER: S-EPMC7530291 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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