A decrease in populations of Bacteroides thetaiotaomicron and Lactobacillus johnsonii is observed during the development of colitis and fungal overgrowth, while restoration of these populations reduces inflammatory parameters and fungal overgrowth in mice. This study investigated the effect of two fatty acids from B. thetaiotaomicron and L. johnsonii on macrophages and Caco-2 cells, as well as their impact on the inflammatory immune response and on Candida glabrata overgrowth in a murine model of dextran sulfate sodium (DSS)-induced colitis. Oleic acid (OA) and palmitic acid (PA) from L. johnsonii and B. thetaiotaomicron were detected during their interaction with epithelial cells from colon samples. OA alone or OA combined with PA (FAs) reduced the expression of proinflammatory mediators in intestinal epithelial Caco-2 cells challenged with DSS. OA alone or FAs increased FFAR1, FFAR2, AMPK, and IL-10 expression in macrophages. Additionally, OA alone or FAs decreased COX-2, TNFα, IL-6, and IL-12 expression in LPS-stimulated macrophages. In the DSS murine model, oral administration of FAs reduced inflammatory parameters, decreased Escherichia coli and Enterococcus faecalis populations, and eliminated C. glabrata from the gut. Overall, these findings provide evidence that OA combined with PA exhibits anti-inflammatory and antifungal properties.

The gastrointestinal (GI) microbiota acts a natural barrier to the proliferation of opportunistic pathogens.Candida glabratais an opportunistic yeast pathogen that has adapted to colonize all segments of the human GI tract. We observed an increase inEscherichia coli,Enterococcus faecalis, andBacteroides vulgatuspopulations, and a decrease inLactobacillus johnsonii,Bacteroides thetaiotaomicron, andBifidobacterium animalisin mice with DSS-induced colitis. This reduction was more pronounced forL. johnsoniiduringC. glabrataovergrowth. In addition,C. glabrataovergrowth increased mouse mortality and inflammatory parameters, and modulated the expression of intestinal receptors and signaling pathways. TheC. glabratacell wall underwent various changes during the course ofC. glabratacolonization, and showed a significant increase in chitin.C. glabratadeficient 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 andC. glabrataovergrowth, while chitinase-3-like protein-1 increased. This study provides evidence that inflammation of the gut alters the microbial balance and leads toC. glabratacell wall remodeling through an increase in chitin, which is involved in promoting persistence ofC. glabratain the gut.

The intestinal microbiota plays a crucial role in the maintenance of gut homeostasis. Changes in crosstalk between the intestinal epithelial cells, immune cells and the microbiota are critically involved in the development of inflammatory bowel disease. In the experimental mouse model, the development of colitis induced by dextran sulfate sodium (DSS) promotes overgrowth of the opportunistic yeast pathogen Candida glabrata. Conversely, fungal colonization aggravates inflammatory parameters. In the present study, we explored the effect of C. glabrata colonization on the diversity of the gut microbiota in a DSS-induced colitis model, and determined the impact of soluble β-glucans on C. glabrata-host interactions. Mice were administered a single inoculum of C. glabrata and were exposed to DSS treatment for 2 weeks in order to induce acute colitis. For β-glucan treatment, mice were administered with soluble β-glucans purified from C. glabrata (3 mg per mouse), orally and daily, for 5 days, starting on day 1. The number of C. glabrata colonies and changes in microbiota diversity were assessed in freshly collected stool samples from each tagged mouse, using traditional culture methods based on agar plates. An increase in Escherichia coli and Enterococcus faecalis populations and a reduction in Lactobacillus johnsonii and Bacteroides thetaiotaomicron were observed during colitis development. This decrease in L. johnsonii was significantly accentuated by C. glabrata overgrowth. Oral administration of β-glucans to mice decreased the overgrowth of aerobic bacteria and IL-1β expression while L. johnsonii and B. thetaiotaomicron populations increased significantly. β-glucan treatment increased IL-10 production via PPARγ sensing, promoting the attenuation of colitis and C. glabrata elimination. This study shows that the colonic inflammation alters the microbial balance, while β-glucan treatment increases the anaerobic bacteria and promotes colitis attenuation and C. glabrata elimination.

Candidiasis, caused by the opportunistic yeast Candida albicans, is the most common fungal infection today. Resistance of C. albicans to current antifungal drugs has emerged over the past decade leading to the need for novel antifungal agents. Our aim was to select new antifungal compounds by library-screening methods and to assess their antifungal effects against C. albicans. After screening 90 potential antifungal compounds from JUNIA, a chemical library, two compounds, 1-(4-chlorophenyl)-4-((4-chlorophenyl)amino)-3,6-dimethylpyridin-2(1H)-one (PYR) and (Z)-N-(2-(4,6-dimethoxy-1,3,5-triazin-2-yl)vinyl)-4-methoxyaniline (TRI), were identified as having potential antifungal activity. Treatment with PYR and TRI resulted in a significant reduction of C. albicans bioluminescence as well as the number of fungal colonies, indicating rapid fungicidal activity. These two compounds were also effective against clinically isolated fluconazole- or caspofungin-resistant C. albicans strains. PYR and TRI had an inhibitory effect on Candida biofilm formation and reduced the thickness of the mannan cell wall. In a Caenorhabditis elegans infection model, PYR and TRI decreased the mortality of nematodes infected with C. albicans and enhanced the expression of antimicrobial genes that promote C. albicans elimination. Overall, PYR and TRI showed antifungal properties against C. albicans by exerting fungicidal activities and enhancing the antimicrobial gene expression of Caenorhabditis elegans.

Resistance of the opportunistic pathogen Candida albicans to antifungal drugs has increased significantly in recent years. After screening 55 potential antifungal compounds from a chemical library, 2,3-dihydroxy-4-methoxybenzaldehyde (DHMB) was identified as having potential antifungal activity. The properties of DHMB were then assessed in vitro and in vivo against C. albicans overgrowth and intestinal inflammation. Substitution on the aromatic ring of DHMB led to a strong decrease in its biological activity against C. albicans. The MIC of DHMB was highly effective at eliminating C. albicans when compared to that of caspofungin or fluconazole. Additionally, DHMB was also effective against clinically isolated fluconazole- or caspofungin-resistant C. albicans strains. DHMB was administered to animals at high doses. This compound was not cytotoxic and was well-tolerated. In experimental dextran sodium sulphate (DSS)-induced colitis in mice, DHMB reduced the clinical and histological score of inflammation and promoted the elimination of C. albicans from the gut. This finding was supported by a decrease in aerobic bacteria while anaerobic bacteria populations were re-established in mice treated with DHMB. DHMB is a small organic molecule with antifungal properties and anti-inflammatory activity by exerting protective effects on intestinal epithelial cells.