Changes in tea exosome-like nanoparticles fermented by <i>Aspergillus cristatus</i> and the preventive effects on non-alcoholic fatty liver disease

Research on dark tea-derived exosome-like nanoparticles (TELNs) and microbial fermentation-mediated modifications of TELNs remains limited. To comprehensively explore the fermentation-induced alterations in TELNs' physical properties, metabolic composition, and biological functions, a systematic investigation was conducted in this study. Particle size distribution, zeta potential, protein content, and particle concentration of TELNs were characterized and compared before and after <i>Aspergillus cristatus</i> (AC) fermentation using nanoparticle tracking analysis (NTA), dynamic light scattering (DLS), and bicinchoninic acid assay (BCA), respectively. Untargeted metabolomics was employed to profile metabolic changes, while functional assessment was performed in a non-alcoholic fatty liver disease (NAFLD) mouse model. As a result, AC fermentation significantly reduced the particle size of TELNs and increased their yield. It altered the overall metabolite profile of TELNs, and a total of 30 differential metabolites were tentatively identified, mainly including flavonoids, alkaloids, and lipids. Meanwhile, AC fermentation enhanced the blood-lipid-lowering and anti-inflammatory abilities of TELNs in NAFLD mice. This study deepened the understanding of the molecular-level changes during tea fermentation, and offered a new perspective on the applications of dark tea or TELNs in the fields of food science and medical healthcare.