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Bifidobacterium adolescentis prevents diabetes-induced liver injury via pyroptosis attenuation
Seyed Mohammadmahdi Meybodi1, Mohammad Javad Rezazadeh Khabaz2, Andia Vojdani3
1Faculty of Veterinary Medicine, Tabriz Branch, Islamic Azad University, Tabriz, Iran; Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran.
Background:
Non-alcoholic fatty liver disease (NAFLD), along with non-alcoholic steatohepatitis (NASH), lacks definitive therapy and typically remains asymptomatic until reaching advanced stages. Lipid metabolism and inflammation management using probiotics such as Bifidobacterium adolescentis is suggested to alleviate or suppress NAFLD development. Hence, this study aims to investigate the effects of Bifidobacterium adolescentis treatment on mitigating pyroptosis, an inflammatory cell death pathway, in the liver of rats with NAFLD induced by high-fat diet (HFD) and streptozotocin (STZ) administration.
Methods:
Forty 8-week adult male Sprague Dawley rats were divided into four groups. Bifidobacterium adolescentis was administered for 8 and 16 weeks at 4 × 1010 CFU/day to rats fed a high-fat diet (HFD). Subsequently, the mRNA expression levels of pyroptotic-related genes including Cas1, Cas3, Cas11, NLRP3, GSDMD, IL-1β, and NF-κB were quantified in liver tissue using quantitative polymerase chain reaction (qPCR). Histopathological alterations and stereological changes in liver structure, as well as lipid profile (FBG, TG, TC, HDL, LDL), and liver indices (ALT, AST, ALP, LDH), were also evaluated across the different groups.
Results:
Bifidobacterium adolescentis administration significantly reduced the expression levels of NF-κB and pyroptotic-related genes. Additionally, this probiotic effectively reversed the adverse effects of the high-fat diet (HFD) on liver volume, Kupffer cell numbers, and hepatocyte nuclei. Furthermore, it improved the lipid profile and liver indices of rats fed with the HFD.
Conclusion:
This study demonstrates that B. adolescentis supplementation prevents diabetes-induced liver injury by attenuating pyroptosis. These findings suggest that Bifidobacterium adolescentis may be a promising therapeutic approach for managing NAFLD and its associated complications, primarily by modulating key genes associated with pyroptosis and inflammation in rats fed with a high-fat diet.
