John Mac
Senior Member (Voting Rights)
Abstract
Background
While bacterial dysbiosis and metabolic disruptions have been widely implicated in the pathogenesis of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), the contribution of the gut mycobiome remains largely unresolved, particularly in the context of host age.Results
Here, high-throughput internal transcribed spacer (ITS) sequencing was applied to fecal samples from 118 individuals (59 ME/CFS patients and 59 healthy matched controls), stratified into three age cohorts: young (18–34 years), middle-aged (35–55 years), and elderly (56–85 years).ME/CFS patients demonstrated significant alterations in gut fungal community composition and diversity compared to controls, with age-specific patterns emerging upon stratified analysis.
Reduced fungal amplicon sequence variant (ASV) richness was observed in ME/CFS patients within the young (P < 0.001) and middle-aged (P < 0.01) cohorts, while the elderly ME/CFS group unexpectedly exhibited increased alpha diversity.
Principal coordinate analyses based on Bray–Curtis and Jaccard distances robustly differentiated ME/CFS and control groups across all age strata, with the magnitude of separation exceeding that observed in age-unstratified analysis.
Age-dependent discriminatory taxa were identified, including Preussia, Endocarpon, Chlorocillium, and Verticillium in the young cohort; Preussia, Romagnesiella, Aspergillus, and Trichothecium in the middle-aged cohort; and Chaetomium, unclassified Ascomycota, and Chlorocillium in the elderly cohort.
Classification models based on fungal genera achieved an overall accuracy of 65.2% (AUC = 0.786) without age stratification, but predictive performance was markedly enhanced, yielding accuracies of 87.5% (AUC = 1.00), 100% (AUC = 0.911), and 100% (AUC = 1.00) in the young, middle-aged, and elderly cohorts, respectively.
Correlation analyses revealed that taxa positively associated with fatigue severity were consistently depleted in ME/CFS, whereas negatively associated genera were enriched, suggesting that these fungi function primarily as biomarkers of disease burden rather than as causal agents.
Conclusions
These findings underscore the critical importance of age-specific analyses in mycobiome research and highlight gut fungal profiles as promising diagnostic biomarkers for ME/CFS when age is explicitly accounted for.
Age-specific alterations of the gut mycobiome in patients with myalgic encephalomyelitis/chronic fatigue syndrome and identification of potential diagnostic biomarkers - BMC Microbiology
While bacterial dysbiosis and metabolic disruptions have been widely implicated in the pathogenesis of myalgic encephalomyelitis/chronic fatigue syndrome (
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