Lactobacillus rhamnosus GG treatment improves intestinal permeability and modulates microbiota dysbiosis in an experimental model of sepsis.

Abstract

Decrease of 'health-benefiting' microbes and increase of pathogenic bacteria (a condition termed dysbiosis) in intensive care unit patients is considered to induce or aggravate sepsis (gut-origin sepsis). Orally administered probiotics have been effective in the prevention of nosocomial infections. However, the mechanisms of probiotic-induced anti-infection and anti-sepsis remain to be explored. In the present study, 4-week-old C57BL6 mice were orally administrated with Lactobacillus rhamnosus GG (LGG) or normal saline (control) 4 weeks prior to cecal ligation and puncture (CLP). A subset of the mice were sacrificed at 24 h post-CLP, and the others were used for survival studies. Ileum tissues, blood and fecal samples were collected. The survival rate of septic mice pretreated with LGG was significantly improved compared with untreated mice. The levels of inflammatory cytokines were reduced in LGG-pretreated septic mice. A decrease of colonic proliferation and epithelial tight junctions and an increase of colonic apoptosis were observed in control septic CLP+saline mice. LGG pretreatment reversed the colonic proliferation, apoptosis and expression of tight junction proteins to the levels of the sham group. LGG pretreatment improved the richness and diversity of intestinal microbiota in septic mice. The principal coordinates analysis clustering plots revealed a significant separate clustering in microbiota structure between three groups. Bacteria associated with energy consumption, including Bacteroidetes, with opportunistic infection, including Proteobacteria, Staphylococcaceae and Enterococcaceae, lipopolysaccharide producers, including Enterobacteriaceae, and facultative anaerobes, such as Bacteroidaceae and Erysipelotrichaceae, increased in septic mice. By contrast, bacteria associated with energy harvest, including Firmicutes, intestinal barrier function regulators, including Akkermansia, hepatic function regulators, including Coprococcus and Oscillospira, and obligate anaerobes, including Prevotellaceae, decreased in septic mice. With LGG pretreatment, the sepsis-induced microbiota dysbiosis was reversed. The present results elucidated the potential mechanism of LGG treatment in sepsis, by improving intestinal permeability and modulating microbiota dysbiosis.