Prevents Hepatic Damage in a Mouse Model of NASH Induced by a High-fructose High-fat Diet

Introduction: Nonalcoholic steatohepatitis (NASH) is an advanced nonalcoholic fatty liver disease characterized by chronic inflammation and fibrosis. A dysbiosis of the gut microbiota has been associated with the pathophysiology of NASH, and probiotics have proven helpful in its treatment and prevention. Although both traditional and next-generation probiotics have the potential to alleviate various diseases, studies that observe the therapeutic effect of next-generation probiotics on NASH are lacking. Therefore, we investigated whether a next-generation probiotic candidate, , contributed to the mitigation of NASH.

Methods: In this study, we conducted 16S rRNA sequencing analyses in patients with NASH and healthy controls. To test could alleviate NASH symptoms, we isolated four strains (EB-FPDK3, EB-FPDK9, EB-FPDK11, and EB-FPYYK1) from fecal samples collected from four healthy individuals. Mice were maintained on a high-fructose high-fat diet for 16 weeks to induce a NASH model and received oral administration of the bacterial strains. Changes in characteristic NASH phenotypes were assessed via oral glucose tolerance tests, biochemical assays, and histological analyses.

Results: 16S rRNA sequencing analyses confirmed that the relative abundance of reduced significantly in patients with NASH compared to healthy controls ( < 0.05). In the NASH mice, supplementation improved glucose homeostasis, prevented hepatic lipid accumulation, curbed liver damage and fibrosis, restored damaged gut barrier functions, and alleviated hepatic steatosis and liver inflammation. Furthermore, real-time PCR assays documented that the four strains regulated the expression of genes related to hepatic steatosis in these mice.

Discussion: Our study, therefore, confirms that the administration of bacteria can alleviate NASH symptoms. We propose that has the potential to contribute to the next-generation probiotic treatment of NASH.