Plant-Derived Exosomal MicroRNAs Shape the Gut Microbiota

Highlights•Plant exosome-like nanoparticles (ELNs) are taken up by gut bacteria•The lipid composition of ELNs determines uptake by specific bacteria•ELN RNAs affect bacterial genes, notably affecting Lactobacillus production of I3A•ELN-mediated I3A alterations affect IL-22 production, resulting in ameliorated colitisSummaryThe gut microbiota can be altered by dietary interventions to prevent and treat various diseases. However, the mechanisms by which food products modulate commensals remain largely unknown. We demonstrate that plant-derived exosome-like nanoparticles (ELNs) are taken up by the gut microbiota and contain RNAs that alter microbiome composition and host physiology. Ginger ELNs (GELNs) are preferentially taken up by Lactobacillaceae in a GELN lipid-dependent manner and contain microRNAs that target various genes in Lactobacillus rhamnosus (LGG). Among these, GELN mdo-miR7267-3p-mediated targeting of the LGG monooxygenase ycnE yields increased indole-3-carboxaldehyde (I3A). GELN-RNAs or I3A, a ligand for aryl hydrocarbon receptor, are sufficient to induce production of IL-22, which is linked to barrier function improvement. These functions of GELN-RNAs can ameliorate mouse colitis via IL-22-dependent mechanisms. These findings reveal how plant products and their effects on the microbiome may be used to target specific host processes to alleviate disease.Graphical abstract