Molecular phenomics and metagenomics of hepatic steatosis in non-diabetic obese women

Hoyles, L. ORCID: 0000-0002-6418-342X, Fernández-Real, J.-M., Federici, M., Serino, M., Abbott, J., Charpentier, J., Heymes, C., Luque, J.L., Anthony, E., 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. and Dumas, M.-E., 2018. Molecular phenomics and metagenomics of hepatic steatosis in non-diabetic obese women. Nature Medicine, 24 (7), pp. 1070-1080. ISSN 1078-8956

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Abstract

The role of molecular signals from the microbiome and their coordinated interactions with those from the host in hepatic steatosis – notably in obese patients and as risk factors for insulin resistance and atherosclerosis – needs to be understood. We reveal molecular networks linking gut microbiome and host phenome to hepatic steatosis in a cohort of non diabetic obese women. Steatotic patients had low microbial gene richness and increased genetic potential for processing of dietary lipids and endotoxin biosynthesis (notably from Proteobacteria), hepatic inflammation and dysregulation of aromatic and branched-chain amino acid (AAA and BCAA) metabolism. We demonstrated that faecal microbiota transplants and chronic treatment with phenylacetic acid (PAA), a microbial product of AAA metabolism, successfully trigger steatosis and BCAA metabolism. Molecular phenomic signatures were predictive (AUC = 87%) and consistent with the gut microbiome making an impact on the steatosis phenome (>75% shared variation) and, therefore, actionable via microbiome-based therapies.

Item Type: Journal article
Publication Title: Nature Medicine
Creators: Hoyles, L., Fernández-Real, J.-M., Federici, M., Serino, M., Abbott, J., Charpentier, J., Heymes, C., Luque, J.L., Anthony, E., 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. and Dumas, M.-E.
Publisher: Springer Nature Limited
Date: July 2018
Volume: 24
Number: 7
ISSN: 1078-8956
Identifiers:
NumberType
10.1038/s41591-018-0061-3DOI
Divisions: Schools > School of Science and Technology
Depositing User: Jill Tomkinson
Date Added: 10 Aug 2018 11:21
Last Modified: 25 Dec 2018 03:00
URI: http://irep.ntu.ac.uk/id/eprint/34314

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