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Biology subjects

Kreulen, I. A. M.

Publications and source records attributed to Kreulen, I. A. M..

2 recordsLinked to original sources

Typing of feces-derived Candida albicans strains using a novel seven-locus microsatellite panel reveals associations with yeast phenotype in individuals with inflammatory bowel disease

Inflammatory diseases of the human gastrointestinal tract are affected by the microbes that reside in the mucosal surfaces along this tract. Patients with inflammatory bowel diseases (IBD) have altered bacterial and fungal intestinal compositions, including higher levels of fecal Candida yeasts. Ongoing research indicates that genetic and phenotypic diversity of Candida albicans may be linked with disease severity. In this study, we set out to investigate feces-derived C. albicans strains from individuals with Crohns disease, ulcerative colitis, and healthy volunteers through microsatellite-based genotyping and phenotypic assays. A seven-locus microsatellite panel was applied, of which six loci were newly developed. Combined interpretation of minimum spanning networks and principal component analysis (PCA) led to indications that there is no specific lineage of C. albicans that is associated with IBD, but rather that the three study populations do have distinguishable distributions of genotypes. In addition, phenotypic characterization by means of enzyme release assays revealed trends between genotypes and virulence-related enzyme activity. Furthermore, correlations were observed between the clinical inflammation biomarker fecal calprotectin and serum anti- Saccharomyces cerevisiae antibodies, as well as between lipase activity of feces-derived C. albicans strains and serum 1,3-{beta}-glucan levels. We thus show that microsatellite typing can describe genetic diversity of feces-derived C. albicans strains, and that phenotypic diversity of these strains may indeed correlate with fungal genotype or disease. This study opens further possibilities to investigate fecal fungi in relation to severity of inflammation in IBD or in other (intestinal) diseases.

microbiology↗

The epithelial-specific ER stress sensor IRE1β enables host-microbiota crosstalk to affect colon goblet cell development

Epithelial cells lining mucosal surfaces of the gastrointestinal and respiratory tracts uniquely express IRE1{beta} (Ern2), a paralogue of the most evolutionarily conserved endoplasmic reticulum stress sensor IRE1. How IRE1{beta} functions at the host-environment interface and why a second IRE1 paralogue evolved remain incompletely understood. Using conventionally raised and germ-free Ern2-/- mice, we found that IRE1{beta} was required for microbiota-induced goblet cell maturation and mucus barrier assembly in the colon. This occurred only after colonization of the alimentary tract with normal gut microflora, which induced IRE1{beta} expression. IRE1{beta} acted by splicing Xbp1 mRNA to expand ER function and prevent ER stress in goblet cells. Although IRE1 can also splice Xbp1 mRNA, it did not act redundantly to IRE1{beta} in this context. By regulating assembly of the colon mucus layer, IRE1{beta} further shaped the composition of the gut microbiota. Mice lacking IRE1{beta} had a dysbiotic microbial community that failed to induce goblet cell development when transferred into germ-free wild type mice. These results show that IRE1{beta} evolved at mucosal surfaces to mediate crosstalk between gut microbes and the colonic epithelium required for normal homeostasis and host defense.

cell biology↗