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Acknowledgements This work was supported by the Government of Ireland National Development Plan by way of a Department of Agriculture Food and Marine, and Health Research Board FHRI award to the ELDERMET project, as well as by a Science Foundation Ireland award to the Alimentary Pharmabiotic Centre. M.J.C. is funded by a fellowship from the Health Research Board of Ireland. We thank K. O’Donovan and P. Egan for clinical assistance, staff in Cork City and County hospitals for facilitating subject recruitment, S. Wong and B. Clayton for supercomputer access. Author Contributions All authors are members of the ELDERMET consortium (http:// eldermet.ucc.ie). P.W.O.T., E.M.O.C., S.Cu. 1 and R.P.R. managed the project; D.v.S., G.F.F., C.S., J.R.M., F.S., C.H., R.P.R. and PWOT designed the analyses; M.J.C., I.B.J., S.Co. 3 , E.M.O.C., H.M.B.H., M.C., B.L., O.O.S., A.P.F., S.E.P., M.W. and L.B. performed the analyses; J.D. performed DNA extraction and PCR; M.W. and L.B. performed NMR metabolomics; M.O.C., N.H., K.O.C. and D.O.M. performed clinical analyses; M.J.C., I.B.J., S.Co. 3 , E.M.O.C., L.B., J.R.M., A.P.F., R.P.R., C.H., F.S. and P.W.O.T. wrote the manuscript. AuthorInformation Ampliconsequencedata,andshotgunsequencedata,contigs,genes and annotations, have been deposited in MG-RAST under the Project ID 154 (http:// metagenomics.anl.gov/linkin.cgi?project154). Reprints and permissions information is available at www.nature.com/reprints. The authors declare no competing financial interests. Readers are welcome to comment on the online version of this article at www.nature.com/nature. Correspondence and requests for materials should be addressed to P.W.O.T. (pwotoole@ucc.ie).

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