Lactobacillus paracasei CNCM I-3689 reduces vancomycin-resistant Enterococcus persistence and promotes Bacteroidetes resilience in the gut following antibiotic challenge

Mélanie Foulon,Lionel Rigottier-Gois,Claire Cherbuy,Muriel Derrien,Johan E T Van Hylckama Vlieg,Benjamin Chalin,Laureen Crouzet,Gianfranco Grompone,Sandra Plancade,Pascale Serror

doi:10.1038/s41598-018-23437-9

Abstract

Enterococci, in particular vancomycin-resistant enterococci (VRE), are a leading cause of hospital-acquired infections. Promoting intestinal resistance against enterococci could reduce the risk of VRE infections. We investigated the effects of two Lactobacillus strains to prevent intestinal VRE. We used an intestinal colonisation mouse model based on an antibiotic-induced microbiota dysbiosis to mimic enterococci overgrowth and VRE persistence. Each Lactobacillus spp. was administered daily to mice starting one week before antibiotic treatment until two weeks after antibiotic and VRE inoculation. Of the two strains, Lactobacillus paracasei CNCM I-3689 decreased significantly VRE numbers in the feces demonstrating an improvement of the reduction of VRE. Longitudinal microbiota analysis showed that supplementation with L. paracasei CNCM I-3689 was associated with a better recovery of members of the phylum Bacteroidetes. Bile salt analysis and expression analysis of selected host genes revealed increased level of lithocholate and of ileal expression of camp (human LL-37) upon L. paracasei CNCM I-3689 supplementation. Although a direct effect of L. paracasei CNCM I-3689 on the VRE reduction was not ruled out, our data provide clues to possible anti-VRE mechanisms supporting an indirect anti-VRE effect through the gut microbiota. This work sustains non-antibiotic strategies against opportunistic enterococci after antibiotic-induced dysbiosis.

Highlights

The human gastrointestinal (GI) tract is colonised by a dense and diverse microbial community referred to as the gut microbiota
We used this model to examine the effect of the strains L. paracasei CNCM I-3689 and L. rhamnosus CNCM I-3690 on the colonisation and persistence of E. faecalis V583 according to the experimental protocol depicted in Supplementary Figure S1
After an adaptation period (D0), mice received a daily dose of 109 colony-forming units (CFU) of strain L. paracasei CNCM I-3689, L. rhamnosus CNCM I-3690 or control solution for the duration of the experiment (D21)

Summary

Introduction

The human gastrointestinal (GI) tract is colonised by a dense and diverse microbial community referred to as the gut microbiota This highly complex microbial ecosystem is involved in many host physiological processes including improvement of the intestinal epithelial barrier, education of the immune system, and nutrient acquisition[1]. We previously adapted an E. faecalis colonisation model in mice with conventional microbiota as developed by Donskey et al.[34,35] In this model, mice are pre-treated with clindamycin that causes an imbalance of the gut microbiota including an increase of endogenous enterococci and allows transient colonisation of E. faecalis V583 strain, a representative of the leading hospital adapted lineage of E. faecalis in the United States and in several European countries[36,37]. The effect of this strain on the gut microbiota and on the expression of a selection of host genes was analysed leading us to propose that part of the L. paracasei CNCM I-3689 anti-VRE effect may rely on a faster recovery of members of the phylum Bacteroidetes

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