Immunobiotic bacteria attenuate hepatic fibrosis through the modulation of gut microbiota and the activation of aryl-hydrocarbon receptors pathway in Non-alcoholic steatohepatitis mice. mouse gut metagenome

Probiotics have beneficial roles in reducing intestinal inflammation and gut-associated diseases, but their effects and mechanisms beyond the gut in attenuating the progression of LF are remains unclear. In the present study, a diet-induced NASH/LF mouse model was used to examine the therapeutic potential of immunobiotics on the attenuation of LF and the underlying mechanisms ameliorating the progression of LF. The results showed that a methionine-choline deficient (MCD) diet resulted in hepatic inflammation, steatosis, increased triglyceride and lipid accumulation, inflammatory immune cells, and fibrosis. The MCD diet reduced gut-barrier integrity, mucin production, and inflammatory cytokines and altered the gut microbiota composition that could be restored by immunobiotics. Overall, these results demonstrate a novel insight into the mechanisms through which immunobiotic administration improves the gut barrier integrity, modulates the gut microbial composition, increases AhR activation, and reduces gut dysbiosis, bacterial translocation, LPS, and inflammatory cytokines levels, which in turn in increases the AhR pathway and inhibits HSCs activation and fibrosis progression beyond the gut in the liver tissue of NASH/LF mice.