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Candida albicans  is a commensal yeast present in the gut of most healthy individuals but with highly variable concentrations. However, little is known about the host factors that influence colonization densities. We investigated how microbiota, host lifestyle factors, and genetics could shape  C. albicans  intestinal carriage in 695 healthy individuals from the Milieu Intérieur cohort.  C. albicans  intestinal carriage was detected in 82.9% of the subjects using quantitative PCR. Using linear mixed models and multiway-ANOVA, we explored  C. albicans  intestinal levels with regard to gut microbiota composition and lifestyle factors including diet. By analyzing shotgun metagenomics data and  C. albicans  qPCR data, we showed that  Intestinimonas butyriciproducens  was the only gut microbiota species whose relative abundance was negatively correlated with  C. albicans  concentration. Diet is also linked to  C. albicans  growth, with eating between meals and a low-sodium diet being associated with higher  C. albicans  levels. Furthermore, by Genome-Wide Association Study, we identified 26 single nucleotide polymorphisms suggestively associated with  C. albicans  colonization. In addition, we found that the intestinal levels of  C. albicans  might influence the host immune response, specifically in response to fungal challenge. We analyzed the transcriptional levels of 546 immune genes and the concentration of 13 cytokines after whole blood stimulation with  C. albicans  cells and showed positive associations between the extent of  C. albicans  intestinal levels and  NLRP3  expression, as well as secreted IL-2 and CXCL5 concentrations. Taken together, these findings open the way for potential new interventional strategies to curb  C. albicans  intestinal overgrowth.

Unveiling Candida albicans intestinal carriage in healthy volunteers: the role of micro- and mycobiota, diet, host genetics and immune response