Review Article

Fungal Alterations in Inflammatory Bowel Diseases

Siu Lam; Tao Zuo; Martin Ho; Francis K. L. Chan; Paul K. S. Chan; Siew C. Ng


Aliment Pharmacol Ther. 2019;50(11):1159-1171. 

In This Article

Polymorphic Plasticity of C Albicans in Health and Diseased Animal Models

In the mammalian gut, environmental and nutritional stresses cause C albicans to undergo morphological transformation.[88] The healthy intestinal environment triggers a phenotypic transformation of C albicans by up-regulating the transcription factor White-opaque regulator 1 (WOR1), which is exclusive to Candida species.[88] The adapted form of C albicans is termed Gastrointestinal-indUced Transition (GUT)[88] (Figure 2). Compared to the original yeast form, the GUT form is able to up-regulate genes responsible for fatty acid and N-acetylglucosamine metabolisms whilst down-regulating genes for iron uptake and glycolysis.[88] The polymorphic plasticity allows C albicans to thrive in blood and GI niches, and also allows C albicans to possess an evolvable iron regulatory network to switch between commensalism and virulence depending on its niche.[89] The evolutionary insertion of this transcriptional activator Sef1 promotes iron uptake and virulence in the bloodstream, whereas the indigenous Sfu1 transcriptional repressor allows C albicans to repress iron uptake and avoid iron toxicity in GI niches.[89] It can be inferred that when the GUT form is present, fatty acids are utilised, glycolytic rate is decreased to reduce energy expenditure, and iron toxicity is avoided.[88–90] To date, only C albicans has been reported as the only fungus to possess such characteristics in the mammalian gut, and the presence of GUT form may account for the dominance of C albicans in the gut amongst other intestinal fungi.[88–90] In a healthy mammalian gut, C albicans is exclusively in the GUT form[88,91,92] (Figure 2). While in an immunocompromised host, C albicans is found to be in its hyphal form which preferentially colonises and invades the host mucosa by secretion of aspartyl proteases.[91–93] Expression of enhanced filamentous growth protein 1 (EFG1), a transcription factor responsible for yeast-to-hyphal transition, was found to be significantly elevated in the immunocompromised gastrointestinal (GI) tract, indicating that the condition of host immunity is linked to the morphological state of C albicans.[60,91,92] A recent study also showed that the transformation of C albicans from yeast to hyphae overexpresses candidalysin, a fungal peptide toxin associated with mucosal damage.[94] There remains a lack of data to describe the morphological plasticity of C albicans or other fungi in IBD.

Figure 2.

Candida albicans polymorphic transformation. C albicans passage from oral cavity to gastrointestinal tract along with phenotypical transformation via switching from yeast to Gastrointestinal-indUced Transition (GUT) form. While leaving the gut, it switches back to yeast form, suggesting that the GUT form is adaptive to the human gastrointestinal tract milieu in response to indigestible fatty acid, iron and N-acetylglucosamine (GlcNAc) present in the distal bowel. While the host switches its immunity into an immunocompromised condition, C albicans transforms into its hyphal form that expresses virulence factors and digestive enzymes leading to mucosal damage. Transformation of C albicans is linked to immunity conditions and environmental nutrients, but it is not known if C albicans induces phenotypical transformation in response to inflammatory condition in the gut