Biosafety of hyperbranched polylysine and its regulatory effect on non-alcoholic fatty liver and gut microbiota

Hyperbranched polylysine (HBPL) has shown broad-spectrum antibacterial activity and cell adhesion promoting effect, which are inherited mainly from its ε- and α-structures, respectively. Although the effectiveness of HBPL in wound anti-infection, tissue regeneration and surface modification has been thoroughly demonstrated, its systematic biosafety evaluation and influence on bacterial cohorts in the gut remain unknown. In this study, the biosafety of HBPL was systematically analyzed via endotoxin detection, cytotoxicity test, and acute systemic toxicity test (oral and intravenous injection). On the basis of its excellent biocompatibility (i.e. endotoxin-free, low cytotoxicity, LD50 (oral) ≥ 5000 mg/kg and intravenous injection safety), HBPL was added to high-fat feed for mice. Serum biochemical and hepatic histopathological results revealed that feeding HBPL can significantly reduce lipid accumulation and thus improve mouse liver functions. Additionally, HBPL assists in optimizing gut microbiota via increasing the abundance of beneficial probiotics, including Akkermansia, Butyricicoccus and Romboutsia. These findings suggest that an appropriate dose of HBPL can significantly ameliorate NAFLD through simultaneous lipase inhibition and gut microbiota modulation, providing new insights into the potential application of HBPL in NAFLD treatment.