The gastrointestinal (GI) microbiota acts a natural barrier to the proliferation of opportunistic pathogens. Candida glabrata is an opportunistic yeast pathogen that has adapted to colonize all segments of the human GI tract. We observed an increase in Escherichia coli, Enterococcus faecalis, and Bacteroides vulgatus populations, and a decrease in Lactobacillus johnsonii, Bacteroides thetaiotaomicron, and Bifidobacterium animalis in mice with DSS-induced colitis. This reduction was more pronounced for L. johnsonii during C. glabrata overgrowth. In addition, C. glabrata overgrowth increased mouse mortality and inflammatory parameters, and modulated the expression of intestinal receptors and signaling pathways. The C. glabrata cell wall underwent various changes during the course of C. glabrata colonization, and showed a significant increase in chitin. C. glabrata deficient in chitin synthase-3 induced fewer inflammatory parameters than the parental strain during intestinal inflammation. Oral administration of chitin attenuated the impact of colitis, and reduced the number of aerobic bacteria and C. glabrata overgrowth, while chitinase-3-like protein-1 increased. This study provides evidence that inflammation of the gut alters the microbial balance and leads to C. glabrata cell wall remodeling through an increase in chitin, which is involved in promoting persistence of C. glabrata in the gut.

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 antiinflammatory 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. The gut microbiota plays a crucial role in protecting the host from colonization/infection by pathogens and in stimulating/modulating the immune system 1,2. Alterations to the gut microbiota can occur via changes in the diversity of the bacterial community or by microbiota-host interactions and can be directly correlated with several diseases, in particular inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC) 3. Ulceration from CD can occur anywhere in the gastrointestinal tract while the hallmark of UC is ulceration beginning in the rectum and limited to the colon 4. Although the pathogenesis of IBD is unknown, different studies have reported that changes in gut microbiota biodiversity, genetic susceptibility, environmental factors and the immune system are all involved 5-7. 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 Enterobacteria 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 concentrations 9. Additionally, ineffective bacterial clearance leads to excessive Toll-like receptor (TLR) stimulation, secretion of pro-inflammatory cytokines and activation of the immune response. In a model of dextran sulphate sodium (DSS)-induced colitis, overgrowth of Escherichia coli and Enterococcus faecalis populations, which are representative of the Enterobacteria and Proteobacteria phyla respectively, are associ...