Lactobacillus casei Shirota reshapes the gut microbiota to alleviate excessive inflammation and metabolic disorders in preventing acute liver failure

Millions of people die from liver diseases annually, and liver failure is one of the three major outcomes. The gut microbiota plays a crucial role in liver diseases. This study aimed to explore the effects of Lactobacillus casei strain Shirota (LcS), a probiotic widely used worldwide, on acute liver failure (ALF) and the underlying mechanism. Sprague-Dawley rats were intragastrically administered LcS suspensions or placebo once daily for 7 days before induction of ALF by intraperitoneal injection of D-galactosamine. Histopathological examination and assessments of liver biochemicals, inflammatory cytokines, and the gut microbiota, metabolome and transcriptome were conducted to explore how LcS affects ALF. Our results showed that pretreatment with LcS reduced D-galactosamine-induced hepatic and intestinal damage, as indicated by H&E staining and electron microscope scanning, and reduced the D-galactosamine-induced elevation of serum GGT, TBA, IL-5, IL-10, G-CSF and RANTES. Bacterial 16S rDNA-targeted metagenomic sequencing of the gut microbiota showed that pretreatment with LcS alleviated D-galactosamine-induced depletion of some Bacteroidetes taxa and enrichment of some Firmicutes taxa and lowered the ratio of Firmicutes to Bacteroidetes. Fecal metabolome analysis showed that pretreatment with LcS reduced the D-galactosamine-induced enrichment of metabolites such as chenodeoxycholic acid, deoxycholic acid, lithocholic acid, D-talose and N-acetyl-glucosamine and the depletion of D-glucose and L-methionine. Transcriptome analysis showed that pretreatment with LcS significantly alleviated D-galactosamine-induced downregulation of retinol metabolism and PPAR signaling and upregulation of the pyruvate metabolism pathway in the liver. These results indicated the promising prospects of LcS in the treatment of liver diseases, particularly ALF.