|
|||||
|
|
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 |
|
| Authors: | María Florencia Mascardi Flavia Noelia Mazzini Bárbara Suárez Vera M. Ruda Sebastián Marciano Paola Casciato Adrián Narvaez Leila Haddad Margarita Anders Federico Orozco Ana Jesica Tamaroff Frank Cook John Gounarides Susana Gutt Adrián Gadano Celia Méndez García Martin L. Marro Alberto Penas Steinhardt Julieta Trinks |
| Affiliation: | 1. Instituto de Medicina Traslacional e Ingeniería Biomédica (IMTIB) — CONICET — Instituto Universitario del Hospital Italiano (IUHI) — Hospital Italiano de Buenos Aires (HIBA), Buenos Aires, Argentina Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina;2. Instituto de Medicina Traslacional e Ingeniería Biomédica (IMTIB) — CONICET — Instituto Universitario del Hospital Italiano (IUHI) — Hospital Italiano de Buenos Aires (HIBA), Buenos Aires, Argentina;3. Biotherapeutic and Analytical Technologies, Novartis Institutes for Biomedical Research (NIBR), Cambridge, Massachusetts, USA;4. Liver Unit of Hospital Italiano de Buenos Aires, Buenos Aires, Argentina;5. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina Liver Unit of Hospital Italiano de Buenos Aires, Buenos Aires, Argentina;6. Liver Unit of Hospital Alemán, Buenos Aires, Argentina;7. Nutrition Department of Hospital Italiano de Buenos Aires, Buenos Aires, Argentina;8. Analytical Sciences & Imaging Department, NIBR, Cambridge, Massachusetts, USA;9. Chemical Biology & Therapeutics Department, NIBR, Cambridge, Massachusetts, USA;10. Cardiovascular and Metabolic Disease Area, NIBR, Cambridge, Massachusetts, USA;11. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina Departamento de Ciencias Básicas, Laboratorio de Genómica Computacional, Universidad Nacional de Luján, Lujan, Buenos Aires, Argentina |
| Abstract: | 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. |
| Keywords: | fatty liver microbiota multi-omics network pnpla3 |