Additional Candida albicansadministration enhances the severity of dextran sulfate solution induced colitis mouse model through leaky gut-enhanced systemic inflammation and gut-dysbiosis but attenuated by Lactobacillus rhamnosusL34

ABSTRACTCandida albicansis abundant in the human gut mycobiota but this species does not colonize the mouse gastrointestinal tract. C. albicansadministration in dextran-sulfate solution (DSS) induced-colitis mouse model (DSS+Candida) might resemble more to human condition, therefore, a DSS colitis model with Candidaadministration was studied; first, to test the influence of fungi in DSS model and second, to test the efficacy of Lactobacillus rhamnosusL34. We demonstrated serum (1→3)-β-D-glucan (BG) elevation in patients with IBD and endoscopic moderate colitis in clinical remission, supporting the possible influence of gut fungi toward IBD in human. Then, in mouse model, Candidagavage was found to worsen the DSS model indicated by higher mortality rate, more severe colon histology and enhanced gut-leakage (FITC-dextran assay, endotoxemia, serum BG and blood bacterial burdens) but did not affect weight loss and diarrhea. DSS+Candidainduced higher pro-inflammatory cytokines both in blood and in intestinal tissue. Worsened systemic pro-inflammatory cytokine responses in DSS+Candidacompared with DSS alone was possibly due to the more severe translocation of LPS, BG and bacteria (not fungemia) from gut into systemic circulation. Interestingly, bacteremia from Pseudomonas aeruginosawas more frequently isolated from DSS+Candidathan DSS alone. In parallel, P. aeruginosawas also isolated from fecal culture in most of the mice in DSS+Candidagroup supported by prominent Gammaproteobacteriain fecal microbioata analysis. However, L. rhamnosusL34 attenuated both DSS+Candidaand DSS model through the attenuation of gut local inflammation (cytokines and histology), gut-leakage severity, fecal dysbiosis (culture method and microbiome analysis) and systemic inflammation (serum cytokines). In conclusion, gut Candidain DSS model induced fecal bacterial dysbiosis and enhanced leaky-gut induced bacteremia. Probiotic treatment strategy aiming to reduce gut-fungi and fecal dysbiosis could attenuate disease severity. Investigation on gut fungi in patients with IBD is highly interesting.