Probiotics VSL#3 are effective in reversing non-alcoholic steatohepatitis in a mouse model

Background:Probiotic VSL#3 is used to treat ulcerative colitis.This study examines the effect of VSL#3 in non-alcoholic steatohepatitis(NASH)that has liver carcinogenic potential.Methods:Western diet(WD)-fed wild-type(WT)mice that do not have hepatic inflammation with lymphocyte infiltration and carcinogenic potential were used for baseline comparison.Age-,sex-,and diet-matched bile acid(BA)receptor farnesoid X receptor(FXR)knockout(KO)mice,which developed severe NASH and had the potential for liver cancer development,were supplemented with and without VSL#3 for 7 months.All the mice were euthanized when they were 10 months old.Results:Supplementation with VSL#3 completely abolished hepatic lymphocyte infiltration,reduced hepatic fat content,and improved insulin sensitivity in WD-fed FXR KO mice.In addition,VSL#3 normalized dysregulated BA homoeostasis by inhibiting the classical BA synthesis pathway,inducing the alternative BA pathway,and activating ileal G-protein coupled BA receptor 1(GPBAR1)-regulated signaling.Moreover,VSL#3 reconstructed the gut microbiota by reducing Bacteroidaceae,Porphyromonadaceae,and Helicobacteraceae as well as increasing Lachnospiraceae.Further,VSL#3 enriched the abundance of Ruminococcus and Faecalibacterium,which generate butyrate,at the genus level.It also increased the copy number of the butyrate-producing genes bcoA and buk,suggesting their anti-inflammatory and metabolic effects.Conclusions:VSL#3 is useful in reversing NASH that occurred due to dysregulated BA synthesis and dysbiosis,suggesting its potential in liver cancer prevention.