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

Interaction Between Gut Fungi and Other Microbial Kingdoms in IBD

Polymicrobial Biofilm Formation

An in vitro model showed that S aureus and C albicans aggregate and cooperatively form a biofilm, resulting in increased vancomycin resistance and co-infection aided by C albicans' hyphae. A positive correlation in the abundance between trans-kingdom species C tropicalis, S marcescens and E coli in CD was observed using Ion Torrent sequencing.[58,101] A subsequent in vitro model further demonstrated the synergy between these three microbes by showing the orchestral effect in forming a polymicrobial biofilm.[58,101] These data highlighted that Candida species by themselves may not be the sole contributor to IBD development, but they play a regulatory role in linking microbes from different kingdoms in IBD pathogenesis.

Bacteria Modulates the Active Role of Gut Fungi

How different classes of antibiotics exert inhibitory effect on different bacterial genus spectrum, and how the affected spectrum genus cross-links to the active role of fungi in gut inflammation remains unclear. Two antibiotics, vancomycin and colistin, that target Gram-positive bacteria and Enterobacteriaceae, respectively, have been found to affect the activity of gut fungi and modulate the severity of colitis.[102] Vancomycin inhibited Gram-positive bacteria and provided full protection against colitis whereas colistin-treated mice with Enterobacteriaceae depletion were susceptible to colitis, coupled with silenced colitis-modulating functions of gut fungi.[102] Interestingly, when the gut was colonised by C albicans and S boulardii, Enterobacteriaceae regulated the pathogenic and protective roles of both fungi during the progression of colitis.[102] It was shown that the colonisation level of both fungi was enhanced in the presence of Enterobacteriaceae.[102]

Competition Between Bacteria and Fungi

Apart from the synergistic effect between bacteria and fungi, competition is also seen in the gut.[103,104] The commensal bacteria Bacteroides thetaiotamicron and Blautia producta had a negative correlation in their abundance with C albicans.[103,104] Both bacteria activated Hypoxia-inducible factor 1-alpha (HIF-1α), which is a regulator of innate immunity and cathelicidin LL-37 (an antimicrobial peptide) to oppose C albicans colonisation.[103,104] Commensal bacteria triggered a host response to oppose C albicans colonisation.[33,105] In a preclinical study using a mice model, the use of S cerevisiae CNCM I-3856 strain helped prevent adherent-invasive Escherichia coli (AIEC) from adhering to an inflamed intestinal mucosa, resulting in the amelioration of colitis.[106]

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