Plant-Derived Exosomal MicroRNAs Shape the Gut Microbiota

TLDR

Plant exosome‑like nanoparticles are absorbed by gut bacteria, and their lipid composition dictates bacterial uptake; the RNAs carried by these vesicles modulate bacterial gene expression, notably increasing Lactobacillus indole‑3‑carboxaldehyde production, which in turn stimulates IL‑22 and can ameliorate colitis. The study aims to uncover how plant‑derived exosome‑like nanoparticles influence gut bacterial communities and host physiology. Ginger exosome‑like nanoparticles are preferentially absorbed by Lactobacillaceae, delivering microRNAs that upregulate indole‑3‑carboxaldehyde production and trigger IL‑22 secretion, thereby improving intestinal barrier function and alleviating colitis in mice. These results suggest that plant products can be harnessed to modulate the microbiome and target host pathways for disease relief.

Abstract

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