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

Abstract

Candida albicans; Colonization resistance; Metagenomics

Candida albicans; Resistència a la colonització; Metagenòmica

Candida albicans; Resistencia a la colonización; Metagenómica

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.

This work was supported by a grant from Agence Nationale de la Recherche (FunComPath ANR-14-IFEC-0004), the French Government’s Investissement d’Avenir program (Laboratoire d’Excellence Integrative Biology of Emerging Infectious Diseases [ANR10-LABX-62-IBEID], and [ANR-10-LABX-69-01]), the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie action, Innovative Training Network (FunHoMic; Grant No. 812969), and the European Union’s Horizon 2020 Research and Innovation Program (HDM-FUN, Grant No. 847507). AWW and the Rowett Institute (University of Aberdeen) received core funding support from the Scottish Government’s Rural and Environmental Sciences and Analytical Services (RESAS).