Integrated analysis of the transcriptome and its interaction with the metabolome in metabolic associated fatty liver disease: Gut microbiome signatures, correlation networks, and effect of PNPLA3 genotype

Interactions between communities of the gut microbiome and with the host could affect the onset and progression of metabolic associated fatty liver disease (MAFLD), and can be useful as new diagnostic and prognostic biomarkers. In this study, we performed a multi-omics approach to unravel gut microb...

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Published in:Proteomics (Weinheim) 2023-09, Vol.23 (18), p.e2200414
Main Authors: Mascardi, María Florencia, Mazzini, Flavia Noelia, Suárez, Bárbara, Ruda, Vera M, Marciano, Sebastián, Casciato, Paola, Narvaez, Adrián, Haddad, Leila, Anders, Margarita, Orozco, Federico, Tamaroff, Ana Jesica, Cook, Frank, Gounarides, John, Gutt, Susana, Gadano, Adrián, García, Celia Méndez, Marro, Martin L, Penas Steinhardt, Alberto, Trinks, Julieta
Format: Article
Language:English
Subjects:
Archaea
Bacteria
Biomarkers
Biopsy
Digestive system
Fatty liver
Genotypes
Intestinal microflora
Liver
Liver diseases
Metabolism
Metabolites
Metabolomics
Methanogenic archaea
Microbiomes
Microbiota
Microorganisms
Phages
Protozoa
Steatosis
Transcriptomes
Transcriptomics
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Summary:Interactions between communities of the gut microbiome and with the host could affect the onset and progression of metabolic associated fatty liver disease (MAFLD), and can be useful as new diagnostic and prognostic biomarkers. In this study, we performed a multi-omics approach to unravel gut microbiome signatures from 32 biopsy-proven patients (10 simple steatosis -SS- and 22 steatohepatitis -SH-) and 19 healthy volunteers (HV). Human and microbial transcripts were differentially identified between groups (MAFLD vs. HV/SH vs. SS), and analyzed for weighted correlation networks together with previously detected metabolites from the same set of samples. We observed that expression of Desulfobacteraceae bacterium, methanogenic archaea, Mushu phage, opportunistic pathogenic fungi Fusarium proliferatum and Candida sorbophila, protozoa Blastocystis spp. and Fonticula alba were upregulated in MAFLD and SH. Desulfobacteraceae bacterium and Mushu phage were hub species in the onset of MAFLD, whereas the activity of Fonticula alba, Faecalibacterium prausnitzii, and Mushu phage act as key regulators of the progression to SH. A combination of clinical, metabolomic, and transcriptomic parameters showed the highest predictive capacity for MAFLD and SH (AUC = 0.96). In conclusion, faecal microbiome markers from several community members contribute to the switch in signatures characteristic of MAFLD and its progression towards SH.
ISSN:1615-9853
1615-9861
1615-9861
DOI:10.1002/pmic.202200414