LC2767 Alleviates Cholestatic Liver Injury and Fibrosis in Bile Duct‐Ligated Mice
Dong‐Yun Lee, Hyo‐Min Jang, Jung‐Woo Shin, Yoon‐Jung Shin, Sung Hye Kim, Seung‐Won Han, Dong‐Hyun KimABSTRACT
Background
LC2767, a mix of
Lactiplantibacillus plantarum
LC27 and
Methods
Mice with cholestatic liver injury were prepared by bile duct ligation (BDL). Biomarker levels were measured by enzyme‐linked immunosorbent assay, quantitative real‐time polymerase chain reaction, immunoblotting, or immunofluorescence staining. The gut microbiota composition was analyzed using the Illumina iSeq 100 platform.
Results
Bile duct ligation (BDL) significantly elevated alanine aminotransferase (ALT), bile acid, and lipopolysaccharide (LPS) levels, accompanied by hepatic inflammation and fibrosis, gut inflammation, and gut microbiota dysbiosis. Oral administration of LC2767 significantly attenuated BDL‐induced elevations in liver injury markers, bile acid, and LPS levels in the blood, collagen‐1, α‐smooth muscle actin, tumor necrosis factor (TNF)‐α, and cytochrome P450 family 7 subfamily A member 1 (CYP7A1) expression, NF‐κB + F4/80 + cell number, and steatosis and fibrosis scores in the liver and TNF‐α expression in the colon. In parallel, LC2767 restored BDL‐suppressed small heterodimer partner (SHP, NR0B2) and farnesoid X receptor (FXR, NR1H4) expression in the liver and colon. LC2767 partially alleviated BDL‐induced gut dysbiosis: It increased BDL‐suppressed Anaerotignaceae and Dehalobacterium _f populations and decreased BDL‐induced AC160630_f and PAC001446_f populations. LC2767 also decreased BDL‐induced LPS levels in the blood and feces.
Conclusion
LC2767 may alleviate cholestatic liver injury and fibrosis, accompanied by changes in FXR/SHP expression, NF‐κB activation, and gut microbiota composition.