Abstract

Vancomycin-resistant Enterococcus (VRE) infection is a serious challenge for clinical management and there is no effective treatment at present. Fecal microbiota transplantation (FMT) and probiotic intervention have been shown to be promising approaches for reducing the colonization of certain pathogenic bacteria in the gastrointestinal tract, however, no such studies have been done on VRE. In this study, we evaluated the effect of FMT and two Lactobacillus strains (Y74 and HT121) on the colonization of VRE in a VRE-infection mouse model. We found that both Lactobacilli strains reduced VRE colonization rapidly. Fecal microbiota and colon mRNA expression analyses further showed that mice in FMT and the two Lactobacilli treatment groups restored their intestinal microbiota diversity faster than those in the phosphate buffer saline (PBS) treated group. Administration of Lactobacilli restored Firmicutes more quickly to the normal level, compared to FMT or PBS treatment, but restored Bacteroides to their normal level less quickly than FMT did. Furthermore, these treatments also had an impact on the relative abundance of intestinal microbiota composition from phylum to species level. RNA-seq showed that FMT treatment induced the expression of more genes in the colon, compared to the Lactobacilli treatment. Defense-related genes such as defensin α, Apoa1, and RegIII were down-regulated in both FMT and the two Lactobacilli treatment groups. Taken together, our findings indicate that both FMT and Lactobacilli treatments were effective in decreasing the colonization of VRE in the gut.

Highlights

  • Vancomycin-resistant Enterococcus(VRE), which was first reported in 1988, has become one of the most important nosocomial pathogens due to the administration of broad-spectrum antibiotics and immunosuppressive agents worldwide (Leclercq et al, 1988; Uttley et al, 1988)

  • Our data showed that the Shannon index of phosphate buffer saline (PBS) group is significantly lower than that of control and Y74-treated mice infected with VRE (Y74) groups, suggesting that VRE infection reduced the diversity of the microbiota and FIGURE 1 | Treatments of Lactobacillus murinus Y74, Lactobacillus plantarum HT121-treated mice infected with VRE (HT121) and Fecal microbiota transplantation (FMT) all decreased the colonization of VRE in VRE-infected mice

  • Within the Bacillus family, antibiotic pretreated VRE infection increased the levels of the genera Enterococcus and Lactobacillus compared with uninfected mice, while FMT, Y74, or HT121 significantly reduced the levels of Enterococcus and Lactobacillus to the levels similar to those seen in uninfected mice (Figures 4C,D)

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Summary

Introduction

Vancomycin-resistant Enterococcus(VRE), which was first reported in 1988, has become one of the most important nosocomial pathogens due to the administration of broad-spectrum antibiotics and immunosuppressive agents worldwide (Leclercq et al, 1988; Uttley et al, 1988). Most VRE infections are caused by Enterococcus Faecium (Paganelli et al, 2015). Antibiotic treatment causes destruction of the healthy gut microbiota and consequent loss of colonization resistance, which in turn promotes VRE growth and allows it to thrive and undergo expansion in the gastrointestinal (GI) tract. Reducing VRE intestinal colonization can limit dissemination and systemic infection

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