The gut, the bad and the harmless: Candida albicans as a commensal and opportunistic pathogen in the intestine

Abstract

Candida albicans is a regular member of the intestinal microbiota in the majority of the human population. This underscores C. albicans' adaptation to life in the intestine without inducing competitive interactions with other microbes, or immune responses detrimental to its survival. However, specific conditions such as a dysbalanced microbiome, a suppression of the immune system, and an impaired intestinal barrier can predispose for invasive, mostly nosocomial, C. albicans infections. Colonization of the intestine and translocation through the intestinal barrier are fundamental aspects of the processes preceding life-threatening systemic candidiasis. Insights into C. albicans' commensal lifestyle and translocation can thus help us to understand how patients develop candidiasis, and may provide leads for therapeutic strategies aimed at preventing infection. In this review, we discuss the commensal lifestyle of C. albicans in the intestine, the role of morphology for commensalism, the influence of diet, and the interactions with bacteria of the microbiota.

Fig. 1:

The key mechanisms preventing a commensal-to-pathogen shift of C. albicans.

Fig. 2:

Mechanisms which contribute to a commensal versus pathogenic life style of C. albicans. A healthy diet feeds a healthy microbiome, which antagonizes colonization and hyphal formation of C. albicans via modulation of chemical, nutritional and physiological conditions. However, C. albicans cells also seem to self-regulate a commensal growth (via the “GUT” phenotype or transcriptional down-regulation of hyphal growth) and some gut niches may be colonized by hypha, which potentially show a near-pathogenic behaviour. Mucus production inhibits hyphal formation and keeps the fungus in distance from epithelial cells, which show resistance to occasionally invading hypha, supported by a healthy immune response. In contrast, treatment with antibiotics and a Western diet can cause a dysbiosis of the microbiome and fungal overgrowth. This normally does not lead to fungal pathogenicity in the gut and the microbiome will return to a balanced state, for example after antibiotic therapy is terminated. However, overgrowth may favour the formation of invasive hypha and further predisposing conditions may lead to translocation through the epithelial barrier. This often includes a lack of epithelial fitness and proliferation as a result of cytostatic therapy or physical damage of the epithelial barrier. Further, a compromised status of the innate immune system can cause a failure of the final line of resistance against invasion into the bloodstream and dissemination to vital organs.