GUT METATRANSCRIPTOMICS AND METABOLOMICS REVEAL ASSOCIATION OF CYSTEINE AND PURINE METABOLISMS WITH METABOLIC ASSOCIATED FATTY LIVER DISEASE (MAFLD)

MAZZINI F; MASCARDI MF; RUDA V; SHILPA P; MANSUR L; WANG Y; COOK F; GOUNARIDES J; MARCIANO S; HADDAD L; TAMAROFF AJ; CASCIATO P; NARVAEZ A; ANDERS M; OROZCO F; GUTT S; GADANO A; MENDEZ GARCIA C; MARRO M; PENAS STEINHARDT A; TRINKS J

Congreso; XXVI Congreso de la Asociación Latinoamericana de Enfermedades del Hígado (ALEH) 2021; 2021

Asociación Latinoamericana de Enfermedades del Hígado (ALEH)

BACKGROUND: Gut microbiome represents a niche for biomarkers discovery to risk-stratify MAFLD patients. However, each population may have unique microbiome signatures. Therefore, studies are needed in Latin America where MAFLD prevalence and severity are high.AIMS: To identify gut metatranscriptome and metabolome signatures associated with MAFLD and steatohepatitis (SH) in Argentina.METHODS: Stool samples, diet, demographic and clinical data were obtained from 33 biopsy-proven patients (12 simple steatosis -SS- and 21 SH) and 19 healthy volunteers (HV). PNPLA3 rs738409 SNP was genotyped. HPLC, flow injection analysis with MS/MS in tandem and MetaboAnalyst-v4.0 were used for metabolomics. RNA-seq was performed in NovaSeq6000®. bioBakery-v1.8 and Maaslin2-v1.2.0 were used for data analysis. RESULTS: BMI was higher in MAFLD, particularly among SH (q=4.49e-06). PNPLA3 GG genotype was more prevalent among SH (q=0.02). After adjusting for BMI, 89 and 53 gene family clusters were differentially expressed between HV and MAFLD and between SS and SH, respectively (q