Multi-Omics Analysis Reveals the Potential Preventive Mechanism of Lactobacillus salivarius Li01 Against L-Arginine-Induced Acute Pancreatitis in Mice.

Abstract

Acute pancreatitis (AP) pathogenesis involves gut microbiota dysbiosis. Although Lactobacillus salivarius Li01 (Li01) is a well-characterised probiotic strain, its specific role in AP via the 'gut-pancreas axis' remains unclear. Li01 pretreatment via oral gavage was assessed in an L-arginine-induced AP mouse model. The gut microbiota composition and abundance were analysed via 16S rRNA sequencing, complemented by untargeted faecal metabolomics and pancreatic transcriptomics analyses. Li01 pretreatment significantly alleviated histopathological damage to the pancreas and reduced serum amylase activity in AP model mice. Pancreatic transcriptomic analysis revealed that Li01 modulated the expression of 89 differentially expressed genes (DEGs), thereby impacting key immune-related signalling pathways, including the TNF-α signalling pathway. Furthermore, Li01 mitigated gut microbiota dysbiosis in AP mice, notably by increasing the relative abundance of bacteria such as Paramuribaculum. Faecal metabolomics analysis indicated that Li01 intervention significantly increased the levels of metabolites involved in steroid hormone biosynthesis, including 17α-estradiol. Li01 may alleviate AP by modulating the gut microbiota composition, increasing the relative abundance of bacteria such as Paramuribaculum, and regulating faecal metabolite profiles, particularly those involved in the steroid hormone biosynthesis pathway. These modulations, in turn, appear to influence pancreatic inflammation-related signalling pathways, including the TNF signalling pathway.