Diarrheal microbiota-derived extracellular vesicles drive intestinal homeostasis dysfunction via miR-125b/NF-κB-mediated macrophage polarization.

ABSTRACT: Gut microbiota-derived extracellular vesicles (EVs) are emerging mediators of microbiota-host crosstalk, but their roles in diarrheal diseases remain poorly understood. Here, we revealed that EVs isolated from diarrheal donors' intestinal microbiota trigger pro-inflammatory macrophage polarization and compromise intestinal epithelial barrier integrity in both conventional and pseudo-germ-free mice, demonstrating their intrinsic pathogenicity independent of viable microbes. miRNAs sequencing analysis identified miR-125b as a highly enriched miRNA in diarrheal microbiota-derived EVs, which directly targets the 3' untranslated region of NF-κBIA, leading to its degradation and subsequent activation of the NF-κB signaling pathway. This molecular cascade drives macrophages toward a pro-inflammat

SUBMITTER: Song M 

PROVIDER: S-EPMC12320886 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature