Inflammatory bowel disease (IBD) is a chronic relapsing-remitting disorder of the gastrointestinal tract characterized by immune dysregulation, epithelial barrier dysfunction, and microbial imbalance. While bacterial dysbiosis, including depletion of short-chain fatty acid (SCFA) producers and enrichment of pathobionts, is well characterized, the gut virome and mycobiome remain comparatively neglected. Both exhibit high variability and are constrained by sequencing bias, contamination, and incomplete reference databases, leaving much of the viral and fungal diversity unresolved. Emerging evidence links fungal and viral dysbiosis to IBD pathogenesis, including Candida overgrowth, loss of Saccharomyces, expansion of Caudoviricetes phages, and detection of eukaryotic viruses such as Cytomegalovirus and Epstein-Barr virus in inflamed mucosa. These alterations disrupt barrier integrity, modulate immune signaling, and interact with bacteria and archaea in cross-kingdom networks that amplify inflammation. Translationally, the virome and mycobiome are now recognized as therapeutic targets, inspiring interventions from pre/probiotics and synbiotics to precision phage therapy and microbiota-based transplantation, including fecal virome transplantation (FVT) and fecal microbiota transplantation (FMT). This review recognizes the challenges and opportunities of studying these neglected kingdoms, reframes IBD dysbiosis and highlights new directions for biomarker discovery and multikingdom microbiota-directed therapies.
Houshyar et al. (Thu,) studied this question.