Citrus Exosome-like Nanoparticles Reversed High-Fat Diet-Induced Microbiota Dysbiosis and Associated Short-Chain Fatty Acid Production

Plant-derived exosome-like nanoparticles possess multifaceted therapeutic properties, such as attenuating inflammation, counteracting oxidative damage, and suppressing neoplastic growth. Nevertheless, their modulatory effects on the ecological dynamics of gut microbiota require further elucidation. In this research, citrus exosome-like nanoparticles (CELNs) were successfully isolated and purified, and their structure, composition, and properties were comprehensively characterized. To evaluate the influence of CELNs on gut microbial homeostasis disrupted by a high-fat diet, CELNs were administered orally at three different doses. The results revealed that CELNs significantly reduce the relative abundance of the pathogenic bacterium Prerotellamassilia timonensis while increasing beneficial bacterium ( Acetatifactor muris and Phocaeicola sartorii ) in HFD-fed mice. Concomitantly, CELN treatment elevated short-chain fatty acid (SCFA) concentrations. These findings provided compelling evidence for the potential use of CELNs as dietary supplements to modulate gut microbiota dysbiosis and enhance SCFA metabolism.