Human gut microbes impact host serum metabolome and insulin sensitivity

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Item Type:	Article
Title:	Human gut microbes impact host serum metabolome and insulin sensitivity
Creators Name:	Pedersen, H.K., Gudmundsdottir, V., Nielsen, H.B., Hyotylainen, T., Nielsen, T., Jensen, B.A.H., Forslund, K., Hildebrand, F., Prifti, E., Falony, G., Le Chatelier, E., Levenez, F., Doré, J., Mattila, I., Plichta, D.R., Pöhö, P., Hellgren, L.I., Arumugam, M., Sunagawa, S., Vieira-Silva, S., Jørgensen, T., Holm, J.B., Trošt, K., Kristiansen, K., Brix, S., Raes, J., Wang, J., Hansen, T., Bork, P., Brunak, S., Oresic, M., Ehrlich, S.D. and Pedersen, O.
Abstract:	Insulin resistance is a forerunner state of ischaemic cardiovascular disease and type 2 diabetes. Here we show how the human gut microbiome impacts the serum metabolome and associates with insulin resistance in 277 non-diabetic Danish individuals. The serum metabolome of insulin-resistant individuals is characterized by increased levels of branched-chain amino acids (BCAAs), which correlate with a gut microbiome that has an enriched biosynthetic potential for BCAAs and is deprived of genes encoding bacterial inward transporters for these amino acids. Prevotella copri and Bacteroides vulgatus are identified as the main species driving the association between biosynthesis of BCAAs and insulin resistance, and in mice we demonstrate that P. copri can induce insulin resistance, aggravate glucose intolerance and augment circulating levels of BCAAs. Our findings suggest that microbial targets may have the potential to diminish insulin resistance and reduce the incidence of common metabolic and cardiovascular disorders.
Keywords:	Bacteroides, Branched-Chain Amino Acids, Cardiovascular Diseases, Fasting, Gastrointestinal Microbiome, Glucose Intolerance, Insulin Resistance, Metagenome, Netherlands, Prevotella, Serum, Animals, Mice
Source:	Nature
ISSN:	0028-0836
Publisher:	Nature Publishing Group
Volume:	535
Number:	7612
Page Range:	376-381
Date:	21 July 2016
Official Publication:	https://doi.org/10.1038/nature18646
PubMed:	View item in PubMed

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