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

Disclosures

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

In This Article

Fungal Alterations in Faecal and Mucosa Samples in IBD

Several fungal taxa appeared to be consistently altered during chronic intestinal inflammation. The first human study investigating gut fungal composition of IBD in 2008 used denaturing gradient gel electrophoresis (DGGE)[34] and found an increased diversity of fungi in faecal samples of CD patients. However, the study could not link individual fungal species to IBD due to the lack of sequencing resolution.[34] In 2015, high-throughput 16S ribosomal RNA and Internal transcribed spacer 2 (ITS2) sequencing were performed to evaluate the fungal composition in paediatric IBD faecal samples[27,35] and these studies consistently showed an elevated abundance of Candida species.[27,35] More recently, fungal composition of the faecal microbiota of 235 patients with IBD and 38 healthy subjects was determined using ITS2 sequencing[30] to show an increase in Basidiomycota-to-Ascomycota ratio. One of the most striking features was the increased abundance of Basidiomycota in IBD and particularly during disease flare, which was balanced by an equivalent decrease in Ascomycota.[30] Basidiomycota and Ascomycota abundances exhibited a strong negative correlation with each other.[30] Although Ascomycota was skewed in this ratio, the relative abundance of C albicans under the Ascomycota phyla was increased as its absolute quantity was stably unchanged as shown by quantitative PCR reaction.[30] This result suggested that despite a substantial proportional reduction of Ascomycota, C albicans exist in this phylum and colonise normally during inflammation.[30] Table 1 describes the fungal species that have been reported to be associated with IBD.

Interestingly, there was a negative correlation between the abundance of S cerevisiae and C albicans in faecal samples of IBD subjects, suggesting a competition between the two species in the gut.[30]S cerevisiae has been shown to compete with the colonisation and adhesion of C albicans and by suppressing the expression of secreted aspartyl proteases (SAPs) - 2 and 6 in C albicans, it prevents C albicans from transforming into its invasive hyphal form.[36,37]

The abundance change of gut fungi is not only restricted to the faecal microbiome but also occurs in the diseased-mucosa.[38] A mucosa-associated fungus called Malassezia restricta (M restricta) that normally presents in skin and gut mucosa was found in CD mucosa.[38]M restricta has been found to worsen gut inflammation particularly in CD patients who have Caspase recruitment domain-containing protein (CARD)-9S12N polymorphism, suggesting that CARD9 signalling is critical for M restricta sensing.[38] This hypothesis is supported by exacerbated colitis progression when M restricta was colonised in wild type and germ-free mice.[38] Various C-type lectin receptors, Mincle, CARD9 and Dectin-2 have been found to be responsible for M restricta recognition,[38–40] but the function of CARD9S12N remains unknown, and it was found to be associated with several autoimmune diseases, such as IBD and asthma.[38,40] CARD9S12N can facilitate interleukin 5 (IL-5) secretion in alveolar macrophages for a type II immune response but its central role in CD pathogenesis is not understood.[38,40]

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