NEXT GENERATION PROBIOTIC, PHOCAECOLA DOREI, FOR THE TREATMENT OF NON-ALCOHOLIC FATTY LIVER DISEASE

초록

Background: Non-alcoholic fatty liver diseases (NAFLD) is one of most common liver disease, which has no approved treatment except life style modification or exercise. Gut microbiota plays a key role in the pathogenesis of NAFLD through the gut-liver axis and modification of microbiota has been known as a therapeutic target. Phocaeocola dorei showed therapeutic effects in our previous study. We demonstrated the effect of P. dorei on NAFLD and compared with human data. Methods: We used Western diet-induced NAFLD (12 wks) and STAM mice (15 wks). P. dorei, L. lactis and UDCA were administered to oral gavage at a concentration of 109 CFU/g twice a week. NAFLD severity was determined based on liver/body weight, pathology and biochemistry markers. Caecal samples were collected for the metagenomics by 16S rRNA sequencing. Metabolite profiles were obtained from caecum, liver and serum. Human stool samples (healthy control [n = 49] and NAFLD patients [n = 129]) were collected to investigate clinical characteristics of microbiome and biomarker. Results: P.dorei and L.lactis supplementation effectively normalized weight ratio, NAFLD activity score, biochemical markers. In western diet induced NAFLD mice model, P. dorei administration (P = 0.0111) significantly reduce the NAFLD activity score as like positive control L. lactis. The treatment with P. dorei improves α-diversity (Western, 332±27; P. dorei, 363±63) and increase Bacteroidetes (Western,18%; P. dorei, 25%), also shift the gut microbiome and functional biomarker towards control. P. dorei reduced the nuclear atypia (P<0.001) and stage grading (P=0.014). P. dorei increased the diversity at species level in STAM model. P. dorei (P<0.001) reduced TNF-α, CXCL3 (P=0.023), CXCL4 (P=0.006), and CXCL10 (P=0.026) expression compared to western group. The P. dorei administration significantly improved proliferation markers (CDC20 and CCNB2) and serum endotoxin level. Conclusion: P. dorei ameliorate NAFLD progression by modulating lipid accumulation, inflammation, and proliferation, hence P. dorei could be a promising new age probiotic which can be implemented for a new therapeutical approach to NAFLD.