Basic nutritional investigationProbiotic Lactobacillus rhamnosus GG reduces mortality of septic mice by modulating gut microbiota composition and metabolic profiles
Introduction
Sepsis is considered a severe systemic infection triggered by a pathogenic organism [1]. Although current therapies like fluid resuscitation, antibiotics to ameliorate symptoms, and organ protection, there is no cure for this disease [2]. Therefore, the need for sensitive diagnostic techniques and new therapies for sepsis is compelling. Emerging evidence suggests that intestinal epithelial barrier disturbed and breached by sepsis-promoting bacteria escape to the blood, which results in an aggravation of sepsis [3]. Numerous studies have indicated that both richness and diversity of the microbiota in patients with sepsis are different from those of healthy controls [4,5], and probiotic treatment during sepsis is helpful to reduce the mortality induced by disease progression [6,7]. However, the exact effects and the mechanisms involved in probiotic application remain obscure.
At present, based on intestinal microbiota and metabolism analysis, the combination of 16 S ribosomal DNA gene sequencing and untargeted metabolomics technology is becoming a useful method for revealing the underlying mechanism(s) of diseases or treatments of diseases [8]. The 16 S rDNA gene sequencing technology can rapidly and accurately decipher microbiota profile and reveal the alteration of structure of the gut microbiota associated with diseases and different treatments [9]. Metabonomics, an important technology that provides a global metabolic profile of biological samples, detects metabolism changes caused by internal or external stimuli such as disease progression, pathophysiologic status, or drug treatments [10]. In this research, a 16 S rDNA gene sequencing technology and an ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) technology were combined to explore the therapeutic effects of LGG prophylaxis on the host co-microbiota and metabolism in mice with sepsis-induced colon microbiota dysbiosis.
Section snippets
Ethics statement
Male C57 BL6 mice (4 wk old) were purchased from Zhejiang University. The animal experiments were approved by the Animal Experiments Committee of the First Affiliated Hospital, Zhejiang University. Mice were given a standard mouse chow diet and sterile water under pathogen-free conditions.
Reagents and materials
Probiotic LGG (containing 20 × 1010 colony-forming unit (CFU) of live bacteria per capsule) were purchased from Culturelle corporation (ConAgra Foods, Omaha, NE, USA). Acetonitrile, formic acid, and
LGG prophylaxis reduces mortality and bacteremia in septic mice
Our formal research found that LGG prophylaxis was able to improve 7-d survival rate of septic mice (P = 0.029) [12]. There was no significant difference in total mortality between control and LGG-pretreated septic mice; however, the average days until death in LGG prophylaxis septic mice was significantly elevated (P < 0.05; Supplementary Table 1).
To test whether probiotic LGG can alleviate sepsis-induced bacteremia, we cultured the peripheral blood of mice in different treatment groups a 24 h
Discussion
Sepsis and its treatment lead to an adverse gastrointestinal microenvironment [13]. Administration of Lactobacilli was able to induce modifications in human gastrointestinal microbial ecosystem and therefore became a potential therapeutic approach in treatment of several diseases including sepsis [14], [15], [16]. However, few studies have indicated the potential risk for bacteremia after the administration of probiotic [17]. Thus, great care is required in choosing the proper species of
Conclusions
To our knowledge, this was the first study in which a 16 S rDNA gene sequencing technology and an UPLC-QTOF-MS technology were combined to explore the positive effect of LGG on sepsis. We found that prophylactic LGG treatment is able to reduce mortality through rebalancing the colon microbiome and host metabolism in septic mice. Septic mice had higher levels of secondary BA and lower levels of primary BA than LGG-treated mice. LGG alter the composition of bacteria related to BA metabolism, and
Acknowledgments
The authors acknowledge the State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, Medical College, Zhejiang University for their support in 16 S rDNA sequence analysis and UPLC-QTOF-MS manipulation.
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This work was supported by the National Natural Science Foundation of China (grant no: 81771498) and Zhejiang Traditional Chinese Medicine Administration (grant no: 2017-XK-A31). LC participated in the conceptualization and methodology of the study; the software, writing of the original draft, and reviewing and editing the final version. HL participated in the study methodology and formal analysis. YC participated in the visualization. YY participated in the supervision and funding acquisition.