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

Abstract Objective The use of probiotics to reduce mortality of sepsis was supported by a series of clinical research subjects. However, the exactly mechanisms underlying protective effects of probiotic in sepsis has not been elucidated clearly. Methods Mice were fed either probiotic Lactobacillus rhamnosus GG (LGG) 1 or saline 4 weeks before cecum ligation and puncture (CLP) 2 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) 3 -based metabolomics. Results LGG treatment could noticeably reduce mortality of sepsis as well as reverse gut microbiota dysbiosis caused by sepsis. Specifically, LGG reduced conditional pathogenic bacteria, such as Proteobactria and Deferribacteres, LPS producer, like Enterobacteriaceae, facultative anaerobes, including Bacteroidaceae and Erysipelotrichaceae, while increased the abundance of bacteria related to energy harvest, such as Firmicutes, colon barrier restorer, like Akkermansia, liver function regulator, like Coprococcus and Sutterella. Furthermore, the changes in fecal metabolites were prevented by LGG, these changes were found to mainly be correlated with the following pathways: bile acid metabolism, lysophosphatidylcholines metabolism and eicosatetraenoic acid metabolism. Finally, correlation analysis shown that microbiota dysbiosis was closely related to metabolic imbalance. Conclusions Probiotic LGG may has a positive effect on reducing mortality of sepsis through rebalancing the metabolic profiles and gut microbiota.