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

Clinical Studies of Anti-fungal Therapies and Fungal Probiotics in IBD

With documented alterations in gut mycobiota on IBD activity based on data on mycobial profiling, detection and ASCA and quantitative PCR analysis,[30,43] modulation of the fungal community may offer therapeutic approaches to IBD. Fluconazole, an anti-fungal drug, is not a common treatment for IBD, and it is mostly used to eradicate fungal infection, candidiasis or candidaemia in immunocompromised IBD patients.[62,63] IBD patients with single nucleotide polymorphisms and mutations in the major genetic loci have altered function of pathogen-associated molecular patterns (PAMPs) and cytokine production and are more susceptible to fungal infections. Table 2 shows the genetic mutations and single nucleotide polymorphisms associated with increased susceptibility to fungi infections in IBD. In a study of 89 patients with UC, fluconazole was used to treat a group of 20 patients who have been diagnosed with significant fungal colonisation. The fluconazole-treated group showed a significant reduction in the UC activity index compared with other groups treated with mesalazine (mesalamine), azathioprine or probiotic lacidofil.[64] Three pilot studies showed that amphotericin B and itraconazole were promising to treat Histoplasma capsulatum infection in IBD.[65–67] Two studies showed that amphotericin B and itraconazole significantly reduced or completely eradicated H capsulatum in CD;[65,66] one study showed that itraconazole relieved symptoms and attained clinical and endoscopic remission among 67% of IBD patients.[67]

In addition to fungal eradication, replenishing fungal probiotics is another approach that modulates the gut mycobiota. A pilot study of 24 UC patients who had mild to moderate flares and were receiving mesalazine were additionally administrated 250mg of S boulardii three times per day for 4 weeks.[68] Overall, 17 of 24 patients achieved clinical and endoscopic remission at 4 weeks.[69] Two studies reported supplementing S boulardii to CD patients. In one study, 32 patients with CD in clinical remission were randomly assigned to either mesalazine alone or mesalazine plus a preparation of Saccharomyces boulardii 1 g daily for 6 months Clinical relapse based on CDAI was significantly lower in the mesalazine plus probiotic group compared with mesalazine only group (6% vs 38%).[70] A separate study showed that S boulardii significantly reduced stool frequency in 20 CD patients compared to baseline.[71] Table 3 shows the clinical studies of anti-fungal therapies and fungal probiotics in IBD.

Mechanistic studies showed that S boulardii reduced local inflammation by restricting movements of dendritic cells to inflammatory sites.[22,72,73]S boulardii also induced Interleukin 8 (IL-8), Interferon gamma (IFN-γ) and Transforming growth factor beta (TGF-β) secretion and helper T cells deposition in lymph nodes, thereby reducing the total number of T cells.[22,72,73] Another fungal probiotic—Saccharomycopsis fibuligera has emerged as a Saccharomyces strain that showed therapeutic effect in mice but this newly patented probiotic has not been applied to human studies.[22]

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