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@misc{Hoyles:2017,
author = {Hoyles, L and Fernández-Real, JM and Federici, M and Serino, M and Azalbert, V and Blasco, V and Abbott, J and Barton, RH and Puig, J and Xifra, G and Ricart, W and Woodbridge, M and Tomlinson, C and Cardellini, M and Davato, F and Cardolini, I and Porzio, O and Gentilieschi, P and Lopez, F and Foufelle, F and Postic, C and Butcher, SA and Holmes, E and Nicholson, JK and Burcelin, R and Dumas, ME},
title = {Integrated systems biology to study non-alcoholic fatty liver disease in obese women},
type = {Poster},
url = {http://hdl.handle.net/10044/1/52674},
year = {2017}
}

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TY  - GEN
AB  - Objectives: To integrate metagenomic (faecal microbiome), transcriptomic, metabonomic and clinical data to evaluate the contribution of the gut microbiome to the molecular phenome (hepatic transcriptome, plasma and urine metabonome) of non-alcoholic fatty liver disease (NAFLD) independent of clinical confounders in morbidly obese women recruited to the FLORINASH study.Methods: Faecal, liver biopsy, blood and urine samples and data for 28 clinical variables were collected for 56 obese [body mass index (BMI) >35] women from Italy (n = 31) and Spain (n = 25) who elected for bariatric surgery. Confounder analyses of clinical data were done using linear modeling. Histological examination of liver biopsies was used to grade NAFLD (NAFLD activity score: 0, 1, 2, 3). Faecal metagenomes were generated and analysed using the Imperial Metagenomics Pipeline. Differentially expressed genes were identified in hepatic transcriptomes, and analysed using Enrichr, network analyses and Signaling Pathway Impact Analysis. 1H-NMR data were generated for plasma and urinary metabonomes. Clinical, metagenomic, transcriptomic and metabonomic data were integrated using partial Spearman’s correlation, taking confounders (age, body mass index and cohort) into account.Results: NAFLD activity score was anti-correlated with microbial gene richness, and correlated with abundance of Proteobacteria. KEGG analyses of metagenomic data suggested increased microbial processing of dietary lipids and amino acids, as well as endotoxin-related processes related to Proteobacteria. Metabonomic profiles highlighted imbalances in choline metabolism, branched-chain amino acid metabolism and gut-derived microbial metabolites resulting from metabolism of amino acids. NAFLD-associated hepatic transcriptomes were associated with branched-chain amino acid metabolism, endoplasmic reticulum/phagosome, and immune responses associated with microbial infections. Molecular phenomic signatures were stable and predic
AU  - Hoyles,L
AU  - Fernández-Real,JM
AU  - Federici,M
AU  - Serino,M
AU  - Azalbert,V
AU  - Blasco,V
AU  - Abbott,J
AU  - Barton,RH
AU  - Puig,J
AU  - Xifra,G
AU  - Ricart,W
AU  - Woodbridge,M
AU  - Tomlinson,C
AU  - Cardellini,M
AU  - Davato,F
AU  - Cardolini,I
AU  - Porzio,O
AU  - Gentilieschi,P
AU  - Lopez,F
AU  - Foufelle,F
AU  - Postic,C
AU  - Butcher,SA
AU  - Holmes,E
AU  - Nicholson,JK
AU  - Burcelin,R
AU  - Dumas,ME
PY  - 2017///
TI  - Integrated systems biology to study non-alcoholic fatty liver disease in obese women
UR  - http://hdl.handle.net/10044/1/52674
ER  -

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