Abstract

Alterations to the gut microbiota can cause an amplification of the inflammatory response to intestinal pathogens. We assessed the effect of Bacteroides thetaiotaomicron and Lactobacillus johnsonii on the elimination of Candida species and whether restoration of these two anaerobic bacteria could attenuate the development of colitis in mice. In this study, L. johnsonii and B. thetaiotaomicron interacted directly with Candida species and induced a degradation of the fungal cell wall, mediated via chitinase-like and mannosidase-like activities, which promoted the inhibition of Candida species growth. In the DSS-induced colitis model, oral administration of L. johnsonii and B. thetaiotaomicron to mice reduced the overgrowth of Escherichia coli, Enterococcus faecalis and Candida glabrata populations and resulted in a significant reduction in inflammatory parameters. L. johnsonii and B. thetaiotaomicron decreased pro-inflammatory mediators and enhanced the anti-inflammatory cytokine response with high TLR9 expression and chitinase-like protein-1 activation, which promoted the elimination of C. glabrata from the gut. Overall, these findings provide evidence that L. johnsonii and B. thetaiotaomicron decrease the development of colitis mediated by TLR9 and promote the elimination of C. glabrata from the gut via chitinase-like and mannosidase-like activities.

Highlights

  • Alterations to the gut microbiota can cause an amplification of the inflammatory response to intestinal pathogens

  • Based on our previous observations that intestinal inflammation and Candida species promoted a significant decrease in anaerobic bacteria in a murine model of dextran sulphate sodium (DSS)-induced colitis, in particular B. thetaiotaomicron and L. johnsonii, we first assessed whether B. thetaiotaomicron + L. johnsonii could inhibit the growth of C. albicans and C. glabrata, which are the two most frequent causes of human yeast ­infections[14,15]

  • Intestinal inflammation promotes an increase in release of haemoglobin carrying oxygen and reactive oxygen species into the intestinal lumen which creates a microenvironment for facultative anaerobes and a reduction in obligate anaerobes that leads to increased inflammation

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Summary

Introduction

Alterations to the gut microbiota can cause an amplification of the inflammatory response to intestinal pathogens. In the DSS-induced colitis model, oral administration of L. johnsonii and B. thetaiotaomicron to mice reduced the overgrowth of Escherichia coli, Enterococcus faecalis and Candida glabrata populations and resulted in a significant reduction in inflammatory parameters. L. johnsonii and B. thetaiotaomicron decreased pro-inflammatory mediators and enhanced the antiinflammatory cytokine response with high TLR9 expression and chitinase-like protein-1 activation, which promoted the elimination of C. glabrata from the gut. Numerous studies have shown that the quality and composition of the microbiota are altered in IBD patients, with a reduction of Firmicutes and Bacteroidetes and an increase in Proteobacteria and E­ nterobacteria[8] These alterations to the gut microbiota can cause an amplification of the inflammatory response to intestinal pathogens and trigger a range of mechanisms including increased epithelial permeability and decreased luminal IgA c­ oncentrations[9]. In addition to the DSS-colitis model, the direct effect of these two bacteria on C. glabrata growth/viability were analysed in vitro

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