Molecular phenomics and metagenomics of hepatic steatosis in non-diabetic obese women
Lesley Hoyles
1
,
Jose Manuel Fernández Real
2
,
Massimo Federici
3
,
Matteo Serino
4, 5
,
James Abbott
1
,
Julie Charpentier
4, 5
,
Christophe Heymes
4, 5
,
Jessica Latorre
2
,
Élodie Anthony
6
,
Richard H Barton
1
,
Julien Chilloux
1
,
Antonis Myridakis
1
,
Laura Martinez Gili
1
,
José María Moreno-Navarrete
2
,
Fadila Benhamed
6
,
Vincent Azalbert
4, 5
,
Vincent Blasco Baque
4, 5
,
Josep Puig
2
,
Gemma Xifra
2
,
Wifredo Ricart
2
,
Christopher Tomlinson
1
,
Mark Woodbridge
1
,
Marina Cardellini
3
,
Francesca Davato
3
,
Iris Cardolini
3
,
Ottavia Porzio
7, 8
,
Paolo Gentileschi
7
,
Frédéric Lopez
4, 5
,
Fabienne FOUFELLE
9
,
Sarah A Butcher
1
,
Elaine Holmes
1
,
Jeremy K Nicholson
1
,
Catherine Postic
6
,
Rémy Burcelin
4, 5
,
M. Dumas
1
2
6
8
Department of Laboratory Medicine, Bambino Gesù Children’s Hospital, Rome, Italy
|
Publication type: Journal Article
Publication date: 2018-06-25
scimago Q1
wos Q1
SJR: 18.333
CiteScore: 82.4
Impact factor: 50.0
ISSN: 10788956, 1546170X, 17447933
PubMed ID:
29942096
General Biochemistry, Genetics and Molecular Biology
General Medicine
Abstract
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. Metabolic activity of specific human gut microorganisms contributes to liver steatosis in obese women.
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Total citations:
585
Citations from 2024:
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GOST
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Hoyles L. et al. Molecular phenomics and metagenomics of hepatic steatosis in non-diabetic obese women // Nature Medicine. 2018. Vol. 24. No. 7. pp. 1070-1080.
GOST all authors (up to 50)
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Hoyles L., Fernández Real J. M., Federici M., Serino M., Abbott J., Charpentier J., Heymes C., Latorre J., Anthony É., Barton R. H., Chilloux J., Myridakis A., Martinez Gili L., Moreno-Navarrete J. M., Benhamed F., Azalbert V., Blasco Baque V., Puig J., Xifra G., Ricart W., Tomlinson C., Woodbridge M., Cardellini M., Davato F., Cardolini I., Porzio O., Gentileschi P., Lopez F., FOUFELLE F., Butcher S. A., Holmes E., Nicholson J. K., Postic C., Burcelin R., Dumas M. Molecular phenomics and metagenomics of hepatic steatosis in non-diabetic obese women // Nature Medicine. 2018. Vol. 24. No. 7. pp. 1070-1080.
Cite this
RIS
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TY - JOUR
DO - 10.1038/s41591-018-0061-3
UR - https://doi.org/10.1038/s41591-018-0061-3
TI - Molecular phenomics and metagenomics of hepatic steatosis in non-diabetic obese women
T2 - Nature Medicine
AU - Hoyles, Lesley
AU - Fernández Real, Jose Manuel
AU - Federici, Massimo
AU - Serino, Matteo
AU - Abbott, James
AU - Charpentier, Julie
AU - Heymes, Christophe
AU - Latorre, Jessica
AU - Anthony, Élodie
AU - Barton, Richard H
AU - Chilloux, Julien
AU - Myridakis, Antonis
AU - Martinez Gili, Laura
AU - Moreno-Navarrete, José María
AU - Benhamed, Fadila
AU - Azalbert, Vincent
AU - Blasco Baque, Vincent
AU - Puig, Josep
AU - Xifra, Gemma
AU - Ricart, Wifredo
AU - Tomlinson, Christopher
AU - Woodbridge, Mark
AU - Cardellini, Marina
AU - Davato, Francesca
AU - Cardolini, Iris
AU - Porzio, Ottavia
AU - Gentileschi, Paolo
AU - Lopez, Frédéric
AU - FOUFELLE, Fabienne
AU - Butcher, Sarah A
AU - Holmes, Elaine
AU - Nicholson, Jeremy K
AU - Postic, Catherine
AU - Burcelin, Rémy
AU - Dumas, M.
PY - 2018
DA - 2018/06/25
PB - Springer Nature
SP - 1070-1080
IS - 7
VL - 24
PMID - 29942096
SN - 1078-8956
SN - 1546-170X
SN - 1744-7933
ER -
Cite this
BibTex (up to 50 authors)
Copy
@article{2018_Hoyles,
author = {Lesley Hoyles and Jose Manuel Fernández Real and Massimo Federici and Matteo Serino and James Abbott and Julie Charpentier and Christophe Heymes and Jessica Latorre and Élodie Anthony and Richard H Barton and Julien Chilloux and Antonis Myridakis and Laura Martinez Gili and José María Moreno-Navarrete and Fadila Benhamed and Vincent Azalbert and Vincent Blasco Baque and Josep Puig and Gemma Xifra and Wifredo Ricart and Christopher Tomlinson and Mark Woodbridge and Marina Cardellini and Francesca Davato and Iris Cardolini and Ottavia Porzio and Paolo Gentileschi and Frédéric Lopez and Fabienne FOUFELLE and Sarah A Butcher and Elaine Holmes and Jeremy K Nicholson and Catherine Postic and Rémy Burcelin and M. Dumas},
title = {Molecular phenomics and metagenomics of hepatic steatosis in non-diabetic obese women},
journal = {Nature Medicine},
year = {2018},
volume = {24},
publisher = {Springer Nature},
month = {jun},
url = {https://doi.org/10.1038/s41591-018-0061-3},
number = {7},
pages = {1070--1080},
doi = {10.1038/s41591-018-0061-3}
}
Cite this
MLA
Copy
Hoyles, Lesley, et al. “Molecular phenomics and metagenomics of hepatic steatosis in non-diabetic obese women.” Nature Medicine, vol. 24, no. 7, Jun. 2018, pp. 1070-1080. https://doi.org/10.1038/s41591-018-0061-3.