Abstract
Aims: Clinical studies showed that the use of probiotics during critical illness reduced nosocomial infection and improved clinical outcome. However, the functional mechanisms of probiotics is remains unclear. Therefore the aim of current study is to explore the protective effects and understand the underlying mechanisms for the beneficial effects of live combined Bacillus subtilis and Enterococcus faecium (LCBE) in cecal ligation puncture (CLP)-induced sepsis.Methods and Results: Seven-week-old C57BL/6J mice were divided into three groups: sham group (6 mice), CLP-control group (20 mice, pretreatment with saline for 7 days before CLP surgery) and CLP-probiotics group (14 mice, pretreatment with LCBE enteric-coated capsules for 7 days before CLP surgery). In survival experiment, mice were monitored for 7 days after CLP. After the procedure, mice were sacrificed, and, serum, and peritoneal lavage fluid were collected and intestinal ileal samples were harvested.Results: Our results showed that the mortality was significantly reduced in mice CLP-probiotics group vs. CLP-control group (P < 0.05). Also, treatment CLP-probiotics group decreased the injury scores CLP-probiotics group when compared to CLP-control group. Additionally, levels of pro-inflammatory cytokines IL-6 and TNF-α levels in the serum and intestinal ileal tissues of CLP-probiotics group were reduced when compared to CLP-control group (P < 0.05). However, no significant differences in anti-inflammatory levels of IL-10 and TGF-β1 were observed between CLP-control and CLP-probiotic groups. Furthermore, our experiments showed that that probiotic treatment suppressed the macrophage activation and transformation from M-type to M1-type, inhibited the mast cells (MCs) degranulation, and activation of AKT (kinase B) pathway.Conclusion: In conclusion, our data shows that probiotics have a protective role in CLP septic mice through reducing intestinal inflammation, altering macrophage polarization and MCs degranulation, and regulating AKT signaling.Significance and Impact of Study: This study demonstrated the protective effects and mechanisms involved in the protective role of live combined Bacillus subtilis and Enterococcus faecium (LCBE) in CLP-induced septic mice model.
Highlights
Sepsis is life threatening organ dysfunction caused by a dysregulated host response to infection, and continues to be the leading cause of mortality in the intensive care unit in developed countries (Hotchkiss et al, 2013; Vincent et al, 2013; Deutschman et al, 2016)
We examined the protective effects of probiotics in cecal ligation puncture (CLP)-induced sepsis, and studied their role in on macrophage activation and transformation, mast cells (MCs) degranulation, and AKT signaling activation
To determine whether live combined Bacillus subtilis and Enterococcus faecium (LCBE) enteric-coated capsules pretreatment could decrease mortality rate in CLP-induced septic mice, 14 mice with LCBE enteric-coated capsules pretreatment and 20 control mice were subjected to CLP surgery, and that six mice were subjected to sham surgery
Summary
Sepsis is life threatening organ dysfunction caused by a dysregulated host response to infection, and continues to be the leading cause of mortality in the intensive care unit in developed countries (Hotchkiss et al, 2013; Vincent et al, 2013; Deutschman et al, 2016). It is essential to study the underlying mechanisms of sepsisinduced gastrointestinal injury and develop novel therapeutic strategies to decrease the morbidity and mortality in septic patients. Numerous studies have reported that macrophages and mast cells (MCs) were implicated in the mediation of sepsis by the modulation of inflammatory and immune responses in a mouse cecal ligation puncture (CLP) model (Gautier et al, 2014; Gautier and Launay, 2015). The exact role of macrophages, remain unclear in sepsis
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