Tryptophan metabolites alleviates Intestinal Candida albicans Infection by reduction of IL-22 releasing from colonic lamina propria group 3 innate lymphoid cells and gut microbiome modification

Abstract

Abstract Background: Invasive candidiasis may be caused by Candida albicans (C. albicans) colonisation of the intestinal tract. Therefore, protection against invasive C. albicansinfections requires a functional intestinal epithelial barrier. Mice infected with Candida albicans in the gut and healthy mice were sampled for faecal analysis. After C. albicans infection, we found significant changes in tryptophan metabolites-kynurenic acid (KynA) and indole acrylate (IA)compared with healthy mice. Results: We identify the mechanism by which KynA and IA ameliorate dextran sulphate sodium (DSS)-induced intestinal C. albicansinfection, based on a systematic analysis of the gut microbiota, metabolomics and transcriptome sequencing in mice. KynA and IA suppress inflammation, upregulate the expression of intestinal tight junctions and reduce IL-22 secretion of colonic lamina propria ILC3 in response of invasive Candida infection. Furthermore, we demonstrated that the gut barrier protection and ILC3 regulation mediated by KynA and IA were dependent on gut microbiota modification by transplanting faecal microbiota into ABX-treated C57BL/6J mice. Conclusion: Our study provides microbiome-to-metabolite alterations in C. albicans gut infection and identifies gut microbiome regulation and IL-22 derived from colonic lamina propria ILC3 as novel targets for C. albicans gut infection therapies.