Beyond Bacteria: The Emerging Role of the Gut Virome and Mycobiome in Celiac Disease.

Background/

Objectives

Celiac disease (CeD) is a complex autoimmune enteropathy triggered by gluten intake in genetically predisposed individuals. While the bacterial microbiome has been extensively studied in CeD, the role of the gut virome and mycobiome is less well defined. Emerging evidence suggests that viruses and fungi may influence mucosal immunity, intestinal permeability and gluten tolerance, acting as potential environmental cofactors in the onset of this disease.

Methods

A narrative review of the literature was conducted to summarize current knowledge of the composition, development and function of the gut virome and mycobiome and to explore their potential involvement in CeD pathogenesis.

Results

The gut virome shows high interindividual variability and dynamic maturation early in life. Multiple studies have associated early enterovirus or parechovirus infections with an increased risk of celiac autoimmunity, supporting a virus-gluten "double hit" model. Viral dysbiosis in CeD has been reported to include an enrichment of human polyomavirus 2 (JC polyomavirus) and of specific enterobacterial phages. The mycobiome, although less abundant, also displays disease-associated alterations: cross-sectional mycobiome studies have reported higher relative abundance of Saccharomyces, Candida, and Tricholomataceae and lower relative abundance of Pichia and Pneumocystis taxa in children with CeD.

Conclusions

Current evidence, although preliminary, supports associations between selected viral exposures and CeD-related immune alterations, whereas current phageome and mycobiome findings mainly describe cross-sectional compositional differences. These data do not establish temporal direction or causality, and further longitudinal and mechanistic investigations are required before preventive or therapeutic implications can be considered.