LAUSR

Summary Diet 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 used Lactobacillus rhamnosus GG (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 tRNAserUCC and tRNAserUCG decay. We identified RNase P, an essential housekeeping endonuclease, being responsible for LELNs-induced tRNAserUCC and tRNAserUCG decay. We further identified galacturonic acid-enriched pectin-type polysaccharide as the active factor in LELNs to increase bile resistance and downregulate tRNAserUCC and tRNAserUCG level in the LGG. Our study demonstrates a tRNA-based gene expression regulation mechanism among lactobacilli to increase bile resistance.