Risk assessment with gut microbiome and metabolite markers in NAFLD development

Howell Leung, Xiaoxue Long, Yueqiong Ni*, Lingling Qian, Emmanouil Nychas, Sara Leal Siliceo, Dennis Pohl, Kati Hanhineva, Yan Liu, Aimin Xu, Henrik B. Nielsen, Eugeni Belda, Karine Clément, Rohit Loomba, Huating Li*, Weiping Jia*, Gianni Panagiotou*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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A growing body of evidence suggests interplay between the gut microbiota and the pathogenesis of nonalcoholic fatty liver disease (NAFLD). However, the role of the gut microbiome in early detection of NAFLD is unclear. Prospective studies are necessary for identifying reliable, microbiome markers for early NAFLD. We evaluated 2487 individuals in a community-based cohort who were followed up 4.6 years after initial clinical examination and biospecimen sampling. Metagenomic and metabolomic characterizations using stool and serum samples taken at baseline were performed for 90 participants who progressed to NAFLD and 90 controls who remained NAFLD free at the follow-up visit. Cases and controls were matched for gender, age, body mass index (BMI) at baseline and follow-up, and 4-year BMI change. Machine learning models integrating baseline microbial signatures (14 features) correctly classified participants (auROCs of 0.72 to 0.80) based on their NAFLD status and liver fat accumulation at the 4-year follow up, outperforming other prognostic clinical models (auROCs of 0.58 to 0.60). We confirmed the biological relevance of the microbiome features by testing their diagnostic ability in four external NAFLD case-control cohorts examined by biopsy or magnetic resonance spectroscopy, from Asia, Europe, and the United States. Our findings raise the possibility of using gut microbiota for early clinical warning of NAFLD development.

Original languageEnglish
Article numbereabk0855
JournalScience Translational Medicine
Issue number648
Number of pages14
Publication statusPublished - 2022


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