Growth dynamics of gut microbiota in health and disease inferred from single metagenomic samples

Tal Korem1,†, David Zeevi1,† , Jotham Suez2,† , Adina Weinberger1,† , Tali Avnit-Sagi1, Maya Pompan-Lotan1, Elad Matot1, Ghil Jona3, Alon Harmelin4, Nadav Cohen1, Alexandra Sirota-Madi5, Christoph A. Thaiss2, Meirav Pevsner-Fischer2,Rotem Sorek6, Ramnik Xavier5, Eran Elinav2,*, Eran Segal1,*

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.

Correspondence to: Eran Elinav2 and Eran Segal1
1 Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel.
2 Immunology Department, Weizmann Institute of Science, Rehovot, Israel
3 Department of Biological services, Weizmann Institute of Science, Rehovot, Israel.
4 Department of Veterinary Resources, Weizmann Institute of Science, Rehovot, Israel.
5 Center for Computational and Integrative Biology, Massachusetts General Hospital, Harvard Medical School and Broad Institute.
6 Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
These authors contributed equally to this work.

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