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The evidence for fungus in Crohn's disease pathogenesis
Jun Miyoshi1, Mark Anthony Sofia1, Joseph Francis Pierre2
1Section of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, The University of Chicago, Chicago, USA.
Abstract:
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.
Insights
Inflammatory bowel diseases (IBD), like Crohn's disease (CD), involve genetic, environmental, and microbial factors. Emerging evidence highlights the role of fungal pathogens in IBD development and recurrence.
Area of Science:
- Gastroenterology and Microbiology
- Immunology
Background:
- Inflammatory bowel diseases (IBD), including Crohn's disease (CD), result from complex interactions between host genetics, environment, and microbial factors.
- Microbial dysbiosis in the gut is increasingly recognized as a key factor in IBD pathogenesis, with bacterial communities extensively studied.
- Recent research suggests a potential role for eukaryotic microorganisms, specifically fungi, in IBD development and chronicity.
Purpose of the Study:
- To review current findings on the role of microbial factors in IBD.
- To explore historical and emerging metagenomic evidence implicating fungal pathogens in Crohn's disease.
- To discuss the contribution of fungi to disease development and recurrence in both adult and pediatric populations.
Main Methods:
- Review of existing literature on IBD etiology and microbiome research.
- Analysis of historical serological data linking fungal targets with CD.
- Examination of metagenomic sequencing data for fungal signatures in CD patients.
Main Results:
- While bacterial dysbiosis is well-documented in CD, emerging evidence points to the involvement of fungi.
- Elevated antibodies against fungal targets have been observed in CD patients, even preceding diagnosis.
- Metagenomic data increasingly supports the association of specific fungi with CD pathogenesis.
Conclusions:
- Microorganisms are necessary but not sufficient for CD development, as shown in germ-free animal models.
- Fungal opportunistic pathogens represent a significant, yet understudied, factor in IBD pathogenesis and chronicity.
- Further research into the fungal microbiome is crucial for understanding and potentially treating IBD in diverse populations.