Richness of human gut microbiome correlates with metabolic markers

Abstract

We are facing a global metabolic health crisis provoked by an obesity epidemic. Here we report the human gut microbial composition in a population sample of 123 non-obese and 169 obese Danish individuals. We find two groups of individuals that differ by the number of gut microbial genes and thus gut bacterial richness. They contain known and previously unknown bacterial species at different proportions; individuals with a low bacterial richness (23% of the population) are characterized by more marked overall adiposity, insulin resistance and dyslipidaemia and a more pronounced inflammatory phenotype when compared with high bacterial richness individuals. The obese individuals among the lower bacterial richness group also gain more weight over time. Only a few bacterial species are sufficient to distinguish between individuals with high and low bacterial richness, and even between lean and obese participants. Our classifications based on variation in the gut microbiome identify subsets of individuals in the general white adult population who may be at increased risk of progressing to adiposity-associated co-morbidities.

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Figure 1: Distribution of low and high gene count individuals (n = 292).
Figure 2: Bacterial species with different distribution among 292 HGC and LGC individuals.
Figure 3: Functional and phylogenetic shifts in the LGC microbiome.
Figure 4: Evolution of BMI in obese and non-obese LGC and HGC individuals (n = 265).

Accession codes

Accessions

European Nucleotide Archive

Data deposits

The raw Illumina read data for all samples has been deposited in the EBI European Nucleotide Archive under the accession number ERP003612.

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Acknowledgements

The authors wish to thank A. Forman, T. Lorentzen, B. Andreasen, G. J. Klavsen and M. M. Andersen for technical assistance; A. L. Nielsen, G. Lademann and M. M. H. Kristensen for management assistance, K. Kiil for discussions and assistance, and A. Walker for comments on the manuscript. This research has received funding from European Community’s Seventh Framework Program (FP7/2007-2013): MetaHIT, grant agreement HEALTH-F4-2007-201052. Additional funding came from The Lundbeck Foundation Centre for Applied Medical Genomics in Personalized Disease Prediction, Prevention and Care (LuCamp, http://www.lucamp.org), ANR MicroObes, the Metagenopolis grant ANR-11-DPBS-0001, Region Ile de France (CODDIM) and Fondacoeur. The Novo Nordisk Foundation Center for Basic Metabolic Research is an independent Research Center at the University of Copenhagen partially funded by an unrestricted donation from the Novo Nordisk Foundation (http://www.metabol.ku.dk).

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O.P. and S.D.E. designed the study, O.P., S.D.E., P.B., W.J., S.B., K.C., J.D., M.K., P.R., T.S.-P., W.M.d.V., T.H., J.R. and K.K. managed the study. T.N., K.B., T.H., N.G., T.J., I.B. and O.P. carried out patient phenotyping and clinical data analyses. T.N., K.B. and F.L. performed sample collection and DNA extraction. J.Q. and J.L. supervised DNA sequencing and gene profiling. S.D.E. and O.P. designed and supervised the data analyses. E.L.C., E.P., T.N., N.G., G.F., F.H., M.Al., M.Ar., J.-M.B., S.K., P.L., N.P., S.S., J.T., J.Q., J.L., J.-D.Z., S.R. and S.D.E. performed the data analyses. S.T. and E.G.Z. carried out HITChip analysis. M.B., A.S.J., H.B.N. and T.S.-P. carried out metagenomic array analyses. S.D.E., O.P., J.R. and P.B. wrote the paper. MetaHIT consortium members provided creative environment and constructive criticism throughout the study.

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Correspondence to Peer Bork or Jun Wang or S. Dusko Ehrlich or Oluf Pedersen.

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The authors declare no competing financial interests.

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Le Chatelier, E., Nielsen, T., Qin, J. et al. Richness of human gut microbiome correlates with metabolic markers. Nature 500, 541–546 (2013). https://doi.org/10.1038/nature12506

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