Risk assessment with gut microbiome and metabolite markers in NAFLD development
Open accessAbstract
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.
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MASH fibrosis is linked to a unique gut microbiome.
“MASH fibrosis is linked to a unique gut microbiome (193-197), and specific microbiome signatures can distinguish human MASH from MASLD (4, 198, 199).”
From Found in translation—Fibrosis in metabolic dysfunction–associated steatohepatitis (MASH) (2023) · cites this paper as [193]
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- Authors
- Leung, H., Long, X., Ni, Y., Qian, L., Nychas, E., Siliceo, S. L., Pohl, D., Hanhineva, K., Liu, Y., Xu, A., Nielsen, H. B., Belda, E., Clément, K., Loomba, R., Li, H., Jia, W., & Panagiotou, G.
- Affiliations
- Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie e. V. - Hans-Knöll-Institut (HKI) (DE)
- Shanghai Jiao Tong University (CN)
- Novo Nordisk Foundation (DK)
- University of Turku (FI)
- University of Hong Kong (HK)
- Clinical Microbiomics (Denmark) (DK)
- Inserm (FR)
- University of California San Diego (US)
- Corresponding author
- Leung, Howell
- Long, Xiaoxue
- Ni, Yueqiong
- Li, Huating
- Jia, Weiping
- Panagiotou, Gianni
- ORCID
- Venue
- Science Translational Medicine
- Published
- 2022-06-08
- Volume
- 14
- Issue
- 648
- Pages
- eabk0855-eabk0855
- ISSN
- 1946-6234 (ISSN-L)
- 1946-6242
- PMC
- PMC9746350
- OpenAlex
- W4282920696
- Cited by
- 152
- References
- 110
- Citations by year
- 2026: 29 · 2025: 49 · 2024: 39 · 2023: 31 · 2022: 4
- FWCI
- 10.04
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science Translational Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- HAL (submittedVersion)
- Technical University of Denmark, DTU Orbit (Technical University of Denmark, DTU) (submittedVersion, other-oa)
- Chalmers Research (Chalmers University of Technology) (submittedVersion)
- Funders
- Innovative Research Team of High-level Local University in Shanghai
- AstraZeneca
- Arrowhead Pharmaceuticals
- Deutsche Forschungsgemeinschaft (H2020-MSCA-ITN-2018 813781, EXC 2051—, 82022012, 390713860)
- National Natural Science Foundation of China (SHSMU-ZDCX20212700, 81561128016, 82022012, 81870598)
- Assistance Publique - Hôpitaux de Paris
- Shanghai Jiao Tong University
- Direction Générale de l’offre de Soins
- Assistance publique-Hôpitaux de Paris
- National Institutes of Health (UL1TR001442)
- Horizon 2020 Framework Programme (MSCA‐ITN‐2018, 813781, H2020-MSCA, H2020-MSCA-ITN-2018, H2020-MSCA-ITN)
- National Health and Medical Research Council (81561128016)
- School of Medicine, Shanghai Jiao Tong University (20191830)
- National Key Research and Development Program of China (2018YFA0800402, SHSMU-ZDCX20212700)
- National Institute on Alcohol Abuse and Alcoholism (U01AA029019)
- National Heart, Lung, and Blood Institute (P01HL147835)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK124318, R01DK121378, R01DK106419, P30DK120515, U01DK061734, U01DK130190)
- National Center for Advancing Translational Sciences
- HORIZON EUROPE Marie Sklodowska-Curie Actions (H2020-MSCA-ITN, H2020, H2020-MSCA-ITN-2018, 813781)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Keywords
- non-alcoholic fatty liver disease, gut microbiota, metabolic biomarkers, early detection, NAFLD risk prediction, hepatic lipid accumulation, metagenomics, metabolomics, machine learning classification, NAFLD progression
- MeSH terms
- Gastrointestinal Microbiome, Humans, Prospective Studies, Biomarkers, Risk Assessment, Non-alcoholic Fatty Liver Disease
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