Cholelithiasis with chronic
cholecystitis is prevalent and threatens human health. Most
cholecystitis caused by
bacterial infection or biofilms is accompanied by
gallstones in the clinic, making gallbladder removal the only effective
solution. Here, we provide a strategy to eliminate
gallstone biofilms and dissolve
gallstones by
oral administration of a supernatant derived from nanoscale
iron sulfide (nFeS supernatant). First, by using
gallstones obtained from the clinic, we simulated biofilm formation on
gallstones and tested the antibacterial activity of a nFeS supernatant in vitro. We found that the supernatant kills bacteria with a 5-log reduction in viability and destroys the biofilm structure. Smashed
gallstones coincubated with E. coli biofilms promote
gallstone formation, while nFeS supernatant can inhibit this process. Second, by using a murine (C57BL/6) model of
cholelithiasis and
cholecystitis, we tested the antibacterial efficacy and
therapeutic effects of nFeS supernatant on
cholelithiasis in vivo. Animal experimental data show that
oral administration of nFeS supernatant can reduce 60% of bacteria in the gallbladder and, remarkably, remove
gallstones with 2 days of treatment compared with clinical
drug combinations (chenodeoxycholid
acid and
ciprofloxacin). Third, by performing
protein abundance analysis of L02 cells and mouse livers, we observed the changes in CYP7a1, HMGCR, and SCP2 expression, indicating that the nFeS supernatant can also regulate
cholesterol metabolism to prevent
gallstone formation. Finally, hematologic biochemistry analysis and high-throughput sequencing technology show that the nFeS supernatant possesses high biocompatibility. Therefore, our work demonstrates that the nFeS supernatant may be a potential regimen for the treatment of
cholelithiasis and
cholecystitis by
oral administration.