Imperial College London
Alternate

ProfessorElaineHolmes

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Professor of Chemical Biology
 
 
 
//

Contact

 

+44 (0)20 7594 3220elaine.holmes

 
 
//

Location

 

661Sir Alexander Fleming BuildingSouth Kensington Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Hoyles:2018:10.1038/s41591-018-0061-3,
author = {Hoyles, L and Fernández-Real, JM and Federici, M and Serino, M and Abbott, J and Charpentier, J and Heymes, C and Latorre, Luque J and Anthony, E and Barton, RH and Chilloux, J and Myridakis, A and Martinez-Gili, L and Moreno-Navarrete, JM and Rayah, F and Azalbert, V and Blasco-Baque, V and Puig, J and Xifra, G and Ricart, W and Tomlinson, C and Woodbridge, M and Cardellini, M and Davato, F and Cardolini, I and Porzio, O and Gentilieschi, P and Lopez, F and Foufelle, F and Butcher, SA and Holmes, E and Nicholson, JK and Postic, C and Burcelin, R and Dumas, ME},
doi = {10.1038/s41591-018-0061-3},
journal = {Nature Medicine},
pages = {1--17},
title = {Molecular phenomics and metagenomics of hepatic steatosis in non-diabetic obese women},
url = {http://dx.doi.org/10.1038/s41591-018-0061-3},
volume = {24},
year = {2018}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Hepatic steatosis is a multifactorial condition that is often observed in obese patients and is a prelude to non-alcoholic fatty liver disease. Here, we combine shotgun sequencing of fecal metagenomes with molecular phenomics (hepatic transcriptome and plasma and urine metabolomes) in two well-characterized cohorts of morbidly obese women recruited to the FLORINASH study. We reveal molecular networks linking the gut microbiome and the host phenome to hepatic steatosis. Patients with steatosis have low microbial gene richness and increased genetic potential for the processing of dietary lipids and endotoxin biosynthesis (notably from Proteobacteria), hepatic inflammation and dysregulation of aromatic and branched-chain amino acid metabolism. We demonstrated that fecal microbiota transplants and chronic treatment with phenylacetic acid, a microbial product of aromatic amino acid metabolism, successfully trigger steatosis and branched-chain amino acid metabolism. Molecular phenomic signatures were predictive (area under the curve = 87%) and consistent with the gut microbiome having an effect on the steatosis phenome (>75% shared variation) and, therefore, actionable via microbiome-based therapies.
AU  - Hoyles,L
AU  - Fernández-Real,JM
AU  - Federici,M
AU  - Serino,M
AU  - Abbott,J
AU  - Charpentier,J
AU  - Heymes,C
AU  - Latorre,Luque J
AU  - Anthony,E
AU  - Barton,RH
AU  - Chilloux,J
AU  - Myridakis,A
AU  - Martinez-Gili,L
AU  - Moreno-Navarrete,JM
AU  - Rayah,F
AU  - Azalbert,V
AU  - Blasco-Baque,V
AU  - Puig,J
AU  - Xifra,G
AU  - Ricart,W
AU  - Tomlinson,C
AU  - Woodbridge,M
AU  - Cardellini,M
AU  - Davato,F
AU  - Cardolini,I
AU  - Porzio,O
AU  - Gentilieschi,P
AU  - Lopez,F
AU  - Foufelle,F
AU  - Butcher,SA
AU  - Holmes,E
AU  - Nicholson,JK
AU  - Postic,C
AU  - Burcelin,R
AU  - Dumas,ME
DO  - 10.1038/s41591-018-0061-3
EP  - 17
PY  - 2018///
SN  - 1078-8956
SP  - 1
TI  - Molecular phenomics and metagenomics of hepatic steatosis in non-diabetic obese women
T2  - Nature Medicine
UR  - http://dx.doi.org/10.1038/s41591-018-0061-3
UR  - https://www.nature.com/articles/s41591-018-0061-3
UR  - http://hdl.handle.net/10044/1/57852
VL  - 24
ER  -
Download