TY - JOUR
T1 - Growth dynamics of gut microbiota in health and disease inferred from single metagenomic samples
AU - Korem, Tal
AU - Zeevi, David
AU - Suez, Jotham
AU - Weinberger, Adina
AU - Avnit Sagi, Sagi, Tali
AU - Pompan-Lotan, Maya
AU - Matot, Elad
AU - Jona, Ghil
AU - Harmelin, Alon
AU - Cohen, Nadav
AU - Sirota-Madi, Alexandra
AU - Thaiss, Christoph Alexander
AU - Pevsner-Fischer, Meirav
AU - Sorek, Rotem
AU - Xavier, Ramnik J.
AU - Elinav, Eran
AU - Segal, Eran
N1 - We thank the members of the Segal and Elinav laboratories for fruitful discussions. T.K. and D.Z. are supported by the Ministry of Science, Technology, and Space, Israel. T.K. is the recipient of the Strauss Institute fellowship for nutritional research. C.A.T. is the recipient of a Boehringer Ingelheim Fonds Ph.D. Fellowship. E.E. is supported by Yael and Rami Ungar, Israel; Leona M. and Harry B. Helmsley Charitable Trust; the Gurwin Family Fund for Scientific Research; Crown Endowment Fund for Immunological Research; estate of Jack Gitlitz; estate of Lydia Hershkovich; the Benoziyo Endowment Fund for the Advancement of Science; Adelis Foundation; John L. and Vera Schwartz, Pacific Palisades; Alan Markovitz, Canada; Cynthia Adelson, Canada; CNRS (Centre National de la Recherche Scientifique); estate of Samuel and Alwyn J. Weber; Mr. and Mrs. Donald L. Schwarz, Sherman Oaks; grants funded by the European Research Council; the German-Israel Binational foundation; the Israel Science Foundation (ISF); the Minerva Foundation; and the Rising Tide foundation. E.E. is the incumbent of the Rina Gudinski Career Development Chair. This work was supported by grants from the European Research Council (ERC) and the ISF to E.S. The European Nucleotide Archive (ENA) accession number for the microbial shotgun sequences is PRJEB9718. The pipeline tool will be made publicly available at http://genie.weizmann.ac.il/software/bac_growth.html. All human studies were approved by the Tel Aviv Sourasky Medical Center Institutional Review Board, approval numbers TLV-0658-12, TLV-0050-13, and TLV-0522-10, and the Weizmann Institute of Science Bioethics and Embryonic Stem Cell Research oversight (ESCRO) committee. The trial was reported to https://clinicaltrials.gov, identifier NCT01892956. The study did not necessitate or involve randomization. Author contributions: T.K. and D.Z. conceived the project, designed and conducted the analyses, interpreted the results, and wrote the manuscript. J.S. devised and performed all experiments in mice, anaerobic, and pathogenic bacteria. A.W. directed some of the experiments and the production of libraries and sequencing from samples collected in this study and provided critical insights to the manuscript. T.K., D.Z., J.S., and A.W. equally contributed to this work. T.A.-S., M.P.-L., and E.M. performed experiments and extraction and sequencing of samples. M.P.-F. performed experiments. G.J. performed chemostat experiments. A.H. supervised germ-free mouse experiments. N.C. aided in the design of the computational pipeline and in conducting the analyses. A.S.-M. and R.J.X. directed the PRISM cohort. C.A.T. and E.E. directed the circadian experiments. R.S. and E.S. directed the dietary intervention study. E.E. and E.S. conceived and directed the project and analyses, designed experiments, interpreted the results, and wrote the manuscript.
PY - 2015/9/4
Y1 - 2015/9/4
N2 - Metagenomic sequencing increased our understanding of the role of the microbiome in health and disease, yet it only provides a snapshot of a highly dynamic ecosystem. Here, we show that the pattern of metagenomic sequencing read coverage for different microbial genomes contains a single trough and a single peak, the latter coinciding with the bacterial origin of replication. Furthermore, the ratio of sequencing coverage between the peak and trough provides a quantitative measure of a species' growth rate. We demonstrate this in vitro and in vivo, under different growth conditions, and in complex bacterial communities. For several bacterial species, peak-to-trough coverage ratios, but not relative abundances, correlated with the manifestation of inflammatory bowel disease and type II diabetes.
AB - Metagenomic sequencing increased our understanding of the role of the microbiome in health and disease, yet it only provides a snapshot of a highly dynamic ecosystem. Here, we show that the pattern of metagenomic sequencing read coverage for different microbial genomes contains a single trough and a single peak, the latter coinciding with the bacterial origin of replication. Furthermore, the ratio of sequencing coverage between the peak and trough provides a quantitative measure of a species' growth rate. We demonstrate this in vitro and in vivo, under different growth conditions, and in complex bacterial communities. For several bacterial species, peak-to-trough coverage ratios, but not relative abundances, correlated with the manifestation of inflammatory bowel disease and type II diabetes.
UR - http://www.scopus.com/inward/record.url?scp=84941368240&partnerID=8YFLogxK
U2 - 10.1126/science.aac4812
DO - 10.1126/science.aac4812
M3 - مقالة
SN - 0036-8075
VL - 349
SP - 1101
EP - 1106
JO - Science (New York, N.Y.)
JF - Science (New York, N.Y.)
IS - 6252
ER -