Characterization of the gut mycobiome in patients with non-alcoholic fatty liver disease and correlations with serum metabolome

BackgroundThe relationship between the gut mycobiome and non-alcoholic fatty liver disease (NAFLD) is largely unexplored. MethodsIn this study, we used a publicly available shotgun metagenomic sequencing dataset of fecal samples to compare the gut fungal communities of 90 NAFLD patients with those of 90 healthy controls. We examined their correlations with gut bacterial communities, host serum metabolite s, and the interactions of key taxa within these networks. ResultsOur results revealed a remarked dysbiosis in the gut mycobiome of NAFLD patients, cha racterized by a significant increase in four fungal taxa, including Pseudopithomyces sp. c174, Muc or sp. c176, Aspergillus sp. c25, and uncultured Ascochyta c213. Multi-omics analysis showed that the gut mycobiome significantly contributes to the host serum metabolome. Pseudopithomyces s p. c174 was notably associated with some beneficial blood metabolites, such as glycoursodeoxycholic acid and alpha-linolenic acid, whereas the NAFLD-enriched pro-inflammatory phenylacetic acid was linked to Aureobasidium sp. c170 and Basipetospora sp. c193. Network analysis revealed significant alterations in the gut microbiome of NAFLD patients, highlighting the potential roles of Alternaria alternata c42, Penicillium sp. c5, and uncultured Malassezia c303. Moreover, predictive models that integrated both bacterial and fungal taxa improved prediction accuracy, emphasizing the crucial role of gut fungi in NAFLD. ImportanceNon-alcoholic fatty liver disease (NAFLD) is a widespread liver condition with limited treatments. While gut bacteria have been extensively studied in NAFLD, the role of gut fungi (the mycobiome) remains poorly understood. This study fills that gap by characterizing gut fungal communities in NAFLD patients and linking these changes to their blood metabolite profiles. We found that NAFLD patients show distinct fungal imbalances, which correlate with key metabolic alterations in the host. These findings expand our understanding of NAFLD by spotlighting gut fungi as important contributors to disease progression. This insight opens new avenues for potential biomarkers and therapies targeting the gut-liver axis. ConclusionsOur findings provide a comprehensive understanding of the link between the gut mycobiome and NAFLD progression, which is essential for guiding future therapeutic research.