The Anti-fibrotic Effects of Heat-Killed Akkermansia muciniphila MucT on Liver Fibrosis Markers and Activation of Hepatic Stellate Cells

Hepatic stellate cell (HSC) activation is a key phenomenon in development of liver fibrosis. Recently, Akkermansia muciniphila has been introduced as a next-generation microbe residing in the mucosal layer of the human gut. Due to the probable risks associated with the use of live probiotics, the tendency to use heat-killed bacteria has been raised. Herein, we investigated the potential anti-fibrotic effects of heat-killed A. muciniphila MucT on activation of HSCs. The human LX-2 cells were stimulated by various concentrations of LPS to evaluate the optimal concentration for HSC activation. Cell viability of LX-2 cells treated with LPS and heat-killed A. muciniphila MucT was measured by MTT assay. Scanning electron microscopy was used to analyze the morphology of heat-killed bacteria. Quiescent and LPS-stimulated LX-2 cells were coinfected with heat-killed A. muciniphila MucT. The gene expression of α-SMA, TIMP, Col1, TGF-β, TLR4, and PPARγ was analyzed using quantitative real-time PCR. Our results showed that LPS treatment led to a significant increase in fibrosis markers in a concentration-independent manner ( P