The evidence for fungus in Crohn’s disease pathogenesis

Current evidence suggests the etiology of inflammatory bowel diseases (IBD) involves the confluence of host genetic, environmental, and microbial factors that lead to chronic, and often refractory, disease in susceptible individuals. The involvement of microbial triggers in IBD, including Crohn’s disease (CD), is increasingly evident with supporting data provided with advancements in metagenomic sequencing that have identified perturbations in microbial structure and function—broadly termed dysbiosis—in CD patients compared with healthy subjects. This concept is supported by the finding germ-free animals with CD genetic susceptibility fail to develop disease; demonstrating microorganisms are necessary but not sufficient for CD. The vast majority of CD microbiome research has focused on the complex bacterial communities and microbiome dysbiosis in the gut with 16S metagenomic sequencing. However, emerging data capturing eukaryotes suggest fungal opportunistic pathogens are also associated with IBD pathogenesis and chronicity. This hypothesis is further supported by historical observations that CD patient populations display elevated antibodies against fungal targets, even evident before disease diagnosis. This review discusses the current findings in the field, followed by historical and metagenomic evidence for fungal pathogens in the development and recurrence of CD in adult and pediatric populations.