Imperial College London
Alternate

ProfessorElaineHolmes

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Professor of Chemical Biology
 
 
 
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Contact

 

+44 (0)20 7594 3220elaine.holmes

 
 
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Location

 

661Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@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 Gentilieshci, P and Lopez, F and Foufelle, F and Postic, C and Butcher, SA and Holmes, E and Nicholson, JK and Burcelin, R and Dumas, MD},
title = {Integrated systems biology to study non-alcoholic fatty liver disease in obese women},
type = {Poster},
url = {http://isappscience.org/2017-annual-meeting/},
year = {2017}
}
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RIS format (EndNote, RefMan)

TY  - GEN
AB  - Metagenomic (faecal microbiome), transcriptomic (liver biopsy), metabonomic (plasma and urine, 1H-NMR) and clinical (28 variables) data were collected for 56 morbidly obese (BMI >35) women from Italy (n = 31) and Spain (n = 25) who elected for bariatric surgery. Data were integrated to evaluate the contribution of the gut microbiome to the molecular phenome (hepatic transcriptome, plasma and urine metabonome) of NAFLD independent of clinical confounders (age, BMI, cohort) using partial Spearman’s correlation. NAFLD activity score (NAS) 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 (BCAA) metabolism and gut-derived microbial metabolites resulting from metabolism of amino acids. NAFLD-associated hepatic transcriptomes were associated with BCAA metabolism, endoplasmic reticulum/phagosome, and immune responses associated with non-specific microbial infections. Molecular phenomic signatures were stable and predictive regardless of sample size, and consistent with the microbiome making a significant contribution to the NAFLD phenome. There is disruption of the gut– liver axis in NAFLD, which can be seen in the gut microbiome, hepatic transcriptome and urinary and plasma metabonomes. Consistency of phenome signatures strongly supports a relationship between microbial amino acid metabolism and microbial gene richness, hepatic gene expression and biofluid metabonomes, and ultimately NAS.
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  - Gentilieshci,P
AU  - Lopez,F
AU  - Foufelle,F
AU  - Postic,C
AU  - Butcher,SA
AU  - Holmes,E
AU  - Nicholson,JK
AU  - Burcelin,R
AU  - Dumas,MD
PY  - 2017///
TI  - Integrated systems biology to study non-alcoholic fatty liver disease in obese women
UR  - http://isappscience.org/2017-annual-meeting/
UR  - http://hdl.handle.net/10044/1/52671
ER  -
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