摘要:SummaryDiet and bile play critical roles in shaping gut microbiota, but the molecular mechanism underlying interplay with intestinal microbiota is unclear. Here, we showed that lemon-derived exosome-like nanoparticles (LELNs) enhance lactobacilli toleration to bile. To decipher the mechanism, we usedLactobacillus rhamnosusGG (LGG) as proof of concept to show that LELNs enhance LGG bile resistance via limiting production of Msp1 and Msp3, resulting in decrease of bile accessibility to cell membrane. Furthermore, we found that decline of Msps protein levels was regulated through specific tRNAserUCCand tRNAserUCGdecay. We identified RNase P, an essential housekeeping endonuclease, being responsible for LELNs-induced tRNAserUCCand tRNAserUCGdecay. We further identified galacturonic acid-enriched pectin-type polysaccharide as the active factor in LELNs to increase bile resistance and downregulate tRNAserUCCand tRNAserUCGlevel in the LGG. Our study demonstrates a tRNA-based gene expression regulation mechanism among lactobacilli to increase bile resistance.Graphical abstractDisplay OmittedHighlights•LELN-derived pectin selectively enhances lactobacilli toleration to bile•LELNs enhance LGG bile resistance via limiting production of Msp1 and Msp3•LELNs decrease translation of Msps via specific tRNAserUCCand tRNAserUCGdecay•LELNs-mediated induction of RNase P is responsible for tRNAserUCCand tRNAserUCGdecayNanoparticles; Molecular biology; Microbiology