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  • 1
    Publication Date: 2015-08-01
    Description: 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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Korem, Tal -- Zeevi, David -- Suez, Jotham -- Weinberger, Adina -- Avnit-Sagi, Tali -- Pompan-Lotan, Maya -- Matot, Elad -- Jona, Ghil -- Harmelin, Alon -- Cohen, Nadav -- Sirota-Madi, Alexandra -- Thaiss, Christoph A -- Pevsner-Fischer, Meirav -- Sorek, Rotem -- Xavier, Ramnik J -- Elinav, Eran -- Segal, Eran -- New York, N.Y. -- Science. 2015 Sep 4;349(6252):1101-6. doi: 10.1126/science.aac4812. Epub 2015 Jul 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel. Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel. ; Immunology Department, Weizmann Institute of Science, Rehovot, Israel. ; Department of Biological services, Weizmann Institute of Science, Rehovot, Israel. ; Department of Veterinary Resources, Weizmann Institute of Science, Rehovot, Israel. ; Center for Computational and Integrative Biology, Massachusetts General Hospital, Harvard Medical School and Broad Institute, Cambridge, MA, USA. ; Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel. ; Immunology Department, Weizmann Institute of Science, Rehovot, Israel. eran.elinav@weizmann.ac.il eran.segal@weizmann.ac.il. ; Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel. Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel. eran.elinav@weizmann.ac.il eran.segal@weizmann.ac.il.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26229116" target="_blank"〉PubMed〈/a〉
    Keywords: Bacteria/classification/genetics/*growth & development ; Diabetes Mellitus, Type 2/*microbiology ; Gastrointestinal Tract/*microbiology ; Genome, Bacterial ; Humans ; Inflammatory Bowel Diseases/*microbiology ; Metagenome ; Metagenomics ; Microbiota/genetics/*physiology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2018-03-23
    Description: Obesity, diabetes, and related manifestations are associated with an enhanced, but poorly understood, risk for mucosal infection and systemic inflammation. Here, we show in mouse models of obesity and diabetes that hyperglycemia drives intestinal barrier permeability, through GLUT2-dependent transcriptional reprogramming of intestinal epithelial cells and alteration of tight and adherence junction integrity. Consequently, hyperglycemia-mediated barrier disruption leads to systemic influx of microbial products and enhanced dissemination of enteric infection. Treatment of hyperglycemia, intestinal epithelial–specific GLUT2 deletion, or inhibition of glucose metabolism restores barrier function and bacterial containment. In humans, systemic influx of intestinal microbiome products correlates with individualized glycemic control, indicated by glycated hemoglobin levels. Together, our results mechanistically link hyperglycemia and intestinal barrier function with systemic infectious and inflammatory consequences of obesity and diabetes.
    Keywords: Immunology, Physiology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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