Lacticaseibacillus paracasei 36 attenuates D-GalN/LPS-induced acute liver injury in mice via suppressing the TLR4/NF-κB/MAPK pathway and NLRP3 inflammasome activation through modulating the intestinal microbiota
Abstract
INTRODUCTION: Acute liver injury (ALI) is a severe clinical syndrome with high mortality, often triggered by toxins, viruses, or immune-mediated injury. The gut-liver axis serves as a key mediator in the progression of hepatic disorders, and probiotics are considered viable treatment options owing to their impact on modulating intestinal microbiota, reducing inflammation, and alleviating oxidative stress.
OBJECTIVES: This study was designed to elucidate the hepatoprotective mechanisms of L. paracasei 36 against D-GalN/LPS-induced ALI in mice, with a specific focus on its roles in inflammation, oxidative stress, apoptosis, and intestinal microbiota regulation.
METHODS: The mice were pretreated with L. paracasei 36 for three weeks prior to the D-GalN/LPS challenge. Serum biomarkers, oxidative damage indicators, inflammatory cytokines, and apoptosis-related genes were measured. Intestinal microbiota composition was analyzed via 16S rRNA sequencing, and hepatic transcriptomics and metabolomics were performed to identify key pathways and metabolites.
RESULTS: L. paracasei 36 pretreatment significantly reduced serum AST, ALT, and TBil levels, alleviated histopathological damage, and decreased oxidative stress and inflammatory cytokine production. It inhibited hepatocyte apoptosis by modulating Bcl-2/Bax expression and suppressed NLRP3 inflammasome activation. L. paracasei 36 restored intestinal microbiota balance, increasing beneficial genera (Ligilactobacillus, Akkermansia) and…
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