BSA-chitosan nanocarrier shields dihydromyricetin from digestive degradation and reshapes gut microbiota and their metabolites in vitro

This study preliminarily confirmed that the primary cause for the low bioavailability of Dihydromyricetin (DHM) was its rapid structural alteration induced by pH fluctuation during digestion, using the in vitro digestion model with HPLC-ESI-MS/MS analysis. Thus, for stable gastrointestinal delivery, DHM was encapsulated using bovine serum albumin (BSA) - chitosan nanocarrier. Physicochemical characterization revealed spherical DHM loaded BSA-chitosan nanoparticles (DBC-NPs, 217.3 ± 3.2 nm) with high encapsulation efficiency (86.66%). In vitro stability tests confirmed their resistance to upper gastrointestinal pH variations and indicated the potential to reach the colon intact. Untargeted metabolomics and 16S rRNA sequencing were performed using in vitro colonic fermentation (three replicates in each group) of gut bacteria from the pooled stools of 6 donors, applying a statistical threshold of p-value <0.05. Furthermore, DBC-NPs modulated gut microbiota (increasing Dorea / Bifidobacterium / Akkermansia , reducing Escherichia-Shigella / Clostridium ) and their corresponding metabolites (such as promoting beneficial phenyllactic acid while inhibiting harmful metabolites such as 3-Oxocholic acid). This study revealed the capability of BSA-chitosan in protecting DHM integrity during digestion and regulative effect on the gut microbiome and their metabolites, offering new strategies for functional foods and precision nutrition interventions.