Review Article

The Gut Microbiome in Inflammatory Bowel Disease—Avenues for Microbial Management

J. McIlroy; G. Ianiro; I. Mukhopadhya; R. Hansen; G. L. Hold

Disclosures

Aliment Pharmacol Ther. 2018;47(1):26-42. 

In This Article

The Role of the Mycobiome

Similar to virome analysis, fungi have long been suspected to play a role in IBD pathogenesis. Anti-Saccharomyces cerevisiae antibodies are well-known markers for CD. In mice, gut inflammation and antibiotic usage have been shown to promote fungal proliferation.[48] Other studies have shown that fungi can modulate susceptibility to inflammation in a negative (Candida albicans) or positive (Saccharomyces boulardii) manner.[49] Finally, mice lacking major genes involved in fungal sensing, such as Dectin-1 or Card9, have an increased fungal microbiota load and are more susceptible to colitis, with human genetic studies also confirming a role for CARD 9.[50,51] Recently, the pace of investigation has gathered momentum, although most clinical studies to date involve small patient cohorts and therefore lack definitive power.

Looking at fungal diversity, the consensus of findings indicates that the 2 major fungal phyla detected in the human gut are Ascomycota and Basidiomycota[50,52–54] and that, numerically, fungal DNA is not a major constituent of the microbiome, with 99.1% of the genetic catalogue from the gut lumen being of bacterial origin, whereas fungal DNA accounts for around 0.02% of the entire mucosa-associated microbiota.[55–58] Mukhopadhya et al were the first to look at the mycobiome in de novo paediatric inflammatory bowel disease patients and noted that there was an overwhelming predominance of the Basidomycota phylum in IBD patients, although sample size was limited, and each patient demonstrated a unique fungal signature.[4] Interestingly, the study was undertaken on mucosal biopsy samples rather than faecal samples. Higher levels of Basidiomycota were recently reported in mucosal biopsies from a treatment naïve paediatric CD cohort from Saudi Arabia compared to control patients.[59] Interestingly, the mycobiome diversity analysis of faecal samples from the same cohort did not show the same fungal profile, highlighting similar findings to bacterial diversity studies which clearly demonstrate differing microbial consortia between mucosal and luminal samples. A mucosa-based study on 23 CD adult patients also demonstrated similar findings.[60]

Sokol et al recently published a larger faecal-based adult inflammatory bowel disease study comprising 235 well-phenotyped inflammatory bowel disease subjects and 38 healthy subjects.[61] They identified a disease-specific fungal dysbiosis with shifts in composition involving the 2 dominant fungal phyla, and several fungal species including S. cerevisiae, Malassezia sympodialis and C. albicans. Bacterial biodiversity was investigated and shown to decrease in both CD and ulcerative colitis; however, fungal biodiversity was decreased only in ulcerative colitis, indicating that a CD -specific gut environment may favour fungi at the expense of bacteria. They explored the equilibrium between bacterial and fungal diversity in the gut and determined that the fungi-to-bacteria diversity ratio was increased in IBD, particularly in ileal CD and flares. Interestingly, an increase in Basidomycota abundance was associated with disease flare, matching the findings of the de novo paediatric studies, which exclusively assessed active disease. Inter-kingdom analysis (bacterial and fungal) was also conducted by Sokol et al, and this demonstrated correlations between bacterial and fungal components with differences seen between inflammatory bowel disease and healthy subjects, suggesting the existence of disease-specific inter-kingdom alterations.

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