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Plasma and stool metabolomics to identify microbiota derived-biomarkers of metabolic dysfunction-associated fatty liver disease: effect of PNPLA3 genotype
- Source :
- Metabolomics : Official journal of the Metabolomic Society. 17(7)
- Publication Year :
- 2021
-
Abstract
- Non-invasive biomarkers are needed for metabolic dysfunction-associated fatty liver disease (MAFLD), especially for patients at risk of disease progression in high-prevalence areas. The microbiota and its metabolites represent a niche for MAFLD biomarker discovery. However, studies are not reproducible as the microbiota is variable. We aimed to identify microbiota-derived metabolomic biomarkers that may contribute to the higher MAFLD prevalence and different disease severity in Latin America, where data is scarce. We compared the plasma and stool metabolomes, gene patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 single nucleotide polymorphism (SNP), diet, demographic and clinical data of 33 patients (12 simple steatosis and 21 steatohepatitis) and 19 healthy volunteers (HV). The potential predictive utility of the identified biomarkers for MAFLD diagnosis and progression was evaluated by logistic regression modelling and ROC curves. Twenty-four (22 in plasma and 2 in stool) out of 424 metabolites differed among groups. Plasma triglyceride (TG) levels were higher among MAFLD patients, whereas plasma phosphatidylcholine (PC) and lysoPC levels were lower among HV. The PNPLA3 risk genotype was related to higher plasma levels of eicosenoic acid or fatty acid 20:1 (FA(20:1)). Body mass index and plasma levels of PCaaC24:0, FA(20:1) and TG (16:1_34:1) showed the best AUROC for MAFLD diagnosis, whereas steatosis and steatohepatitis could be discriminated with plasma levels of PCaaC24:0 and PCaeC40:1. This study identified for the first time MAFLD potential non-invasive biomarkers in a Latin American population. The association of PNPLA3 genotype with FA(20:1) suggests a novel metabolic pathway influencing MAFLD pathogenesis.
- Subjects :
- medicine.medical_specialty
Genotype
Endocrinology, Diabetes and Metabolism
Clinical Biochemistry
Population
Single-nucleotide polymorphism
01 natural sciences
Biochemistry
Gastroenterology
03 medical and health sciences
Non-alcoholic Fatty Liver Disease
Internal medicine
medicine
Humans
Metabolomics
Biomarker discovery
education
030304 developmental biology
chemistry.chemical_classification
0303 health sciences
education.field_of_study
business.industry
Microbiota
010401 analytical chemistry
Fatty liver
Fatty acid
Membrane Proteins
Lipase
medicine.disease
0104 chemical sciences
chemistry
Steatosis
Steatohepatitis
business
Biomarkers
Subjects
Details
- ISSN :
- 15733890
- Volume :
- 17
- Issue :
- 7
- Database :
- OpenAIRE
- Journal :
- Metabolomics : Official journal of the Metabolomic Society
- Accession number :
- edsair.doi.dedup.....1646c618e54ecfc35c168b830af1ab94