Hoyles, L ORCID: https://orcid.org/0000-0002-6418-342X, Fernández-Real, J-M, Federici, M, Serino, M, Abbott, J, Charpentier, J, Heymes, C, Luque, JL, Anthony, E, Barton, RH, Chilloux, J, Myridakis, A, Martinez-Gili, L, Moreno-Navarrete, JM, 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, SA, Holmes, E, Nicholson, JK, 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 |
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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: | Number Type 10.1038/s41591-018-0061-3 DOI |
Divisions: | Schools > School of Science and Technology |
Record created by: | Jill Tomkinson |
Date Added: | 10 Aug 2018 11:21 |
Last Modified: | 25 Dec 2018 03:00 |
URI: | https://irep.ntu.ac.uk/id/eprint/34314 |
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