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

Impact of Fungal Alterations on IBD Diagnosis and Disease Activity

Disease Diagnosis

Mycobial profiling can potentially help to identify and differentiate fungal compositions between IBD patients and healthy controls. Upon targeting the responsible fungi from the sequencing profile, mycobiota-based IBD diagnosis may become possible. Currently, the antibody—Anti-Saccharomyces cerevisiae antibody (ASCA) has been used to target S cerevisiae cell wall antigens, mannose alpha 1,3 mannose, for the diagnosis of CD.[41] Nevertheless, C albicans also express common β-glucan epitopes similar to that of S cerevisiae, suggesting that ASCA as a diagnostic tool may not be specific enough to detect individual fungi.[27,42,43] Various sources of microbes and receptors that express these ubiquitous epitopes might also affect ASCA affinity binding, including mycobacteria M paratuberculosis and the fimH receptor on GP2 on M cells, all of which likely contain the mannose alpha 1,3 mannose epitope for ASCA.[44–47] When serological markers are considered individually, ASCA has the best combined sensitivity and specificity for CD; and pANCA for UC. It has been demonstrated that these two antibodies in combination are more accurate in differentiating CD from UC than when used in isolation.[48]The specificity of ASCA is particularly high in CD, around 41%-76%,[43,49,50] and it is often used to differentiate between CD and UC when the diagnosis is unclear. ASCA is also found more commonly in CD patients with a family history of IBD,[43,49,50] single nucleotide polymorphisms in CARD9 or dectin-1 could be applied to diagnose susceptibility loci in potential subjects.[22,51,52]C albicans is more likely to colonise CD patients (44%) and their first-degree healthy relatives (FDR) (38%) compared to healthy individuals (22%).[43] Although CD patients and their FDR have a higher burden of C albicans colonisation, it is reflected by a higher prevalence of ASCA but not a significant elevation of total antibody level. It is unclear if the increased C albicans colonisation directly contributes to disease activity.[43]S cerevisiae detection in faecal samples based on quantitative PCR was found to be decreased in IBD and during IBD flare but increased in faecal samples of healthy control and IBD subjects in remission.[30] Compared to C albicans, S cerevisiae has a more substantial role in IBD activity.[30]

Disease Activity or Severity

Overall, CD patients experience a higher fungal burden during the inflammatory process, while UC patients have a decreased diversity of gut fungi.[30,53–55] In CD, altered ileal physiology in the terminal ileum impairs the inhibitory effect of antimicrobial peptides on bacteria and bile acid reabsorption.[30,53–55] This altered ileal physiology in CD, which is not present in UC, may facilitate fungal colonisation in the terminal ileum.[30,53–55] This may explain why an increased load of Candida species is a distinctive feature in CD; this increase also correlated with disease activity and severity.

Compared to healthy individuals, the total fungal load was more prominent in the mucosa of CD patients with a 40-fold increase during disease flare.[31] The diversity of genus Dioszegia and Candida was also increased, particularly the expansion of Candida glabrata in the inflamed mucosa; and a concurrent increase in S cerevisiae abundance in the non-inflamed mucosa. The genera Leptosphaeria and Trichosporon were decreased[31] (Table 1).[33,43,56,57] In addition, Filobasidium uniguttulatum were elevated in the non-inflamed mucosa, whereas Xylariales were increased in the inflamed mucosa of CD.[33] Increased relative abundance of S cerevisiae and C glabrata was observed,[33] and a positive correlation between Candida tropicalis and familial CD was also reported.[58] Similar alterations of these two commensal fungi have been reported in patients with immunocompromised gastrointestinal (GI) tract or Irritable bowel syndrome.[59–61]

What remains unknown is whether changes in gut fungi diversity are a cause or a consequence in IBD. Such insights require mechanistic studies in animals, and future work should investigate factors that affect gut fungal colonisation in the gut.