Ecological patterns of the gut mycobiome and microbiome in ulcerative colitis across life stages

Introduction: Age-related variations in the gut microbial communities may influence immune regulation and inflammatory processes in inflammatory bowel diseases (IBD). However, distinguishing age effects from differences in clinical characteristics remains challenging. Methods: We investigated life-stage-associated patterns of the gut microbiome and mycobiome while accounting for clinical heterogeneity between paediatric and adult ulcerative colitis (UC) populations. We analysed 73 targeted metagenomes of bacteria and 69 targeted metagenomes of fungi from 26 paediatric and 47 adult patients with UC. Microbial diversity metrics and multivariate analyses were applied to evaluate community variation, and mucosal immune markers were assessed by ELISA. Clinical variables, including disease activity, duration, and treatment exposure, were considered when interpreting age-related microbial differences. Results: Fungal communities exhibited higher richness in adults and formed distinct age-related clusters in beta-diversity analyses, whereas bacterial composition remained largely comparable across age groups. Children were enriched in inflammation-associated fungi (Saccharomycetes, Aureobasidium, Cladosporium) and depleted in taxa commonly linked to gut health (Clavispora, Vishniacozyma, Betamyces). Stratification by life stage identified young adults as displaying the most pronounced dysbiosis, characterised by Basidiomycota/Ascomycota and Firmicutes/Bacteroidota ratios, and reduced Faecalibacterium prausnitzii abundance. Age-associated immune patterns were observed, with lysozyme levels increasing across life stages, correlating with sIgA, and positively associating with F. prausnitzii, although declining with increasing disease severity. Discussion: Age-related variation was more evident in fungal than bacterial communities, suggesting that host developmental and immunological factors contribute to mycobiome configuration beyond clinical imbalance alone. Together, these findings indicate that life stage is linked to ecological variation of the gut mycobiome and mucosal immune responses in UC, while bacterial communities appear primarily shaped by disease-related factors. The transition from childhood to adulthood may represent a critical window of host-fungal interaction relevant for age-tailored microbiome-based strategies.