Plasma and stool metabolomics to identify microbiota derived-biomarkers of metabolic dysfunction-associated fatty liver disease: effect of PNPLA3 genotype.

Autor: Mazzini FN; Instituto de Medicina Traslacional e Ingeniería Biomédica (IMTIB) - CONICET - Instituto Universitario del Hospital Italiano (IUHI) - Hospital Italiano de Buenos Aires (HIBA), Potosí 4240, C1199ACL, Ciudad Autónoma de Buenos Aires, Argentina., Cook F; Analytical Sciences & Imaging (AS&I) Department, Novartis Institutes for Biomedical Research (NIBR), Cambridge, MA, USA., Gounarides J; Analytical Sciences & Imaging (AS&I) Department, Novartis Institutes for Biomedical Research (NIBR), Cambridge, MA, USA., Marciano S; Liver Unit of Hospital Italiano de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina., Haddad L; Liver Unit of Hospital Italiano de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina., Tamaroff AJ; Nutrition Department of Hospital Italiano de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina., Casciato P; Liver Unit of Hospital Italiano de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina., Narvaez A; Liver Unit of Hospital Italiano de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina., Mascardi MF; Instituto de Medicina Traslacional e Ingeniería Biomédica (IMTIB) - CONICET - Instituto Universitario del Hospital Italiano (IUHI) - Hospital Italiano de Buenos Aires (HIBA), Potosí 4240, C1199ACL, Ciudad Autónoma de Buenos Aires, Argentina., Anders M; Liver Unit of Hospital Alemán, Ciudad Autónoma de Buenos Aires, Argentina., Orozco F; Liver Unit of Hospital Alemán, Ciudad Autónoma de Buenos Aires, Argentina., Quiróz N; Instituto de Medicina Traslacional e Ingeniería Biomédica (IMTIB) - CONICET - Instituto Universitario del Hospital Italiano (IUHI) - Hospital Italiano de Buenos Aires (HIBA), Potosí 4240, C1199ACL, Ciudad Autónoma de Buenos Aires, Argentina., Risk M; Instituto de Medicina Traslacional e Ingeniería Biomédica (IMTIB) - CONICET - Instituto Universitario del Hospital Italiano (IUHI) - Hospital Italiano de Buenos Aires (HIBA), Potosí 4240, C1199ACL, Ciudad Autónoma de Buenos Aires, Argentina., Gutt S; Nutrition Department of Hospital Italiano de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina., Gadano A; Liver Unit of Hospital Italiano de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina., Méndez García C; Chemical Biology & Therapeutics (CBT) Department, NIBR, Cambridge, MA, USA., Marro ML; Cardiovascular and Metabolic Disease Area, NIBR, Cambridge, MA, USA., Penas-Steinhardt A; Laboratorio de Genómica Computacional, Departamento de Ciencias Básicas, Universidad Nacional de Luján, Luján, Buenos Aires, Argentina., Trinks J; Instituto de Medicina Traslacional e Ingeniería Biomédica (IMTIB) - CONICET - Instituto Universitario del Hospital Italiano (IUHI) - Hospital Italiano de Buenos Aires (HIBA), Potosí 4240, C1199ACL, Ciudad Autónoma de Buenos Aires, Argentina. julieta.trinks@hospitalitaliano.org.ar.
Jazyk: angličtina
Zdroj: Metabolomics : Official journal of the Metabolomic Society [Metabolomics] 2021 Jun 16; Vol. 17 (7), pp. 58. Date of Electronic Publication: 2021 Jun 16.
DOI: 10.1007/s11306-021-01810-6
Abstrakt: Introduction: 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.
Objectives: 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.
Methods: 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.
Results: 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.
Conclusion: 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.
Databáze: MEDLINE
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