Faecalibacterium Prausnitzii extracellular vesicles regulating macrophage differentiation via homologous recombination repair in colitis model.

Abstract

Inflammatory Bowel Disease (IBD) is characterized by chronic inflammation influenced by the depletion of beneficial gut microbiota, a critical factor in disease onset and progression. This study investigates the therapeutic potential of extracellular vesicles (EVs) derived from Faecalibacterium prausnitzii (F.p EVs), a commensal bacterium whose reduction is linked to IBD. Our research demonstrates that F.p EVs are preferentially taken up by macrophages, where they exert their anti-inflammatory effects through the enhancement of homologous recombination (HR) repair mechanisms. Specifically, F.p EVs upregulate the expression of key proteins involved in HR repair, such as BRCA1 and BRCA2, thereby reducing DNA damage and inhibiting the cGAS-STING pathway, which is central to the inflammatory response. This modulation of macrophage function results in decreased pro-inflammatory cytokine production and enhanced intestinal barrier integrity. By elucidating these mechanisms, our study provides a clear understanding of how F.p EVs can be used to target fundamental aspects of IBD pathology, laying the groundwork for the development of more effective and targeted therapies.