Probiotic Lactobacillus rhamnosus GG reduces mortality of septic mice by modulating gut microbiota composition and metabolic profiles.

Abstract

The use of probiotics to reduce mortality of sepsis was supported by a series of clinical research subjects. However, the exact mechanisms underlying protective effects of probiotic in sepsis has not been elucidated clearly. The aim of this study was to explore the therapeutic effects of Lactobacillus rhamnosus GG (LGG) prophylaxis on the host co-microbiota and metabolism in mice with sepsis-induced colon microbiota dysbiosis. Mice were fed either probiotic LGG or saline 4 wk before cecum ligation and puncture (CLP) operation. Fecal samples were collected and analyzed by 16S rDNA sequencing and ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS)-based metabolomics. LGG treatment could noticeably reduce the mortality of sepsis and reverse gut microbiota dysbiosis caused by sepsis. Specifically, LGG reduced conditional pathogenic bacteria, such as Proteobactria and Deferribacteres; lipopolysaccharide producers like Enterobacteriaceae, facultative anaerobes, including Bacteroidaceae and Erysipelotrichaceae, and increased the abundance of bacteria related to energy harvest, such as Firmicutes; colon barrier restorers like Akkermansia; and liver function regulators like Coprococcus and Sutterella. Furthermore, the changes in fecal metabolites were prevented by LGG. These changes were found mainly to be correlated with the bile acid and metabolism pathways, lysophosphatidylcholines metabolism, and eicosatetraenoic acid metabolism. Finally, correlation analysis shown that microbiota dysbiosis was closely related to metabolic imbalance. Probiotic LGG may has a positive effect on reducing mortality of sepsis through rebalancing the metabolic profiles and gut microbiota.