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Gut DNA viromes of Malawian twins discordant for severe acute malnutrition.
Proc Natl Acad Sci U S A 2015; 112(38):11941-6PN

Abstract

The bacterial component of the human gut microbiota undergoes a definable program of postnatal development. Evidence is accumulating that this program is disrupted in children with severe acute malnutrition (SAM) and that their persistent gut microbiota immaturity, which is not durably repaired with current ready-to-use therapeutic food (RUTF) interventions, is causally related to disease pathogenesis. To further characterize gut microbial community development in healthy versus malnourished infants/children, we performed a time-series metagenomic study of DNA isolated from virus-like particles (VLPs) recovered from fecal samples collected during the first 30 mo of postnatal life from eight pairs of mono- and dizygotic Malawian twins concordant for healthy growth and 12 twin pairs discordant for SAM. Both members of discordant pairs were sampled just before, during, and after treatment with a peanut-based RUTF. Using Random Forests and a dataset of 17,676 viral contigs assembled from shotgun sequencing reads of VLP DNAs, we identified viruses that distinguish different stages in the assembly of the gut microbiota in the concordant healthy twin pairs. This developmental program is impaired in both members of SAM discordant pairs and not repaired with RUTF. Phage plus members of the Anelloviridae and Circoviridae families of eukaryotic viruses discriminate discordant from concordant healthy pairs. These results disclose that apparently healthy cotwins in discordant pairs have viromes associated with, although not necessarily mediators, of SAM; as such, they provide a human model for delineating normal versus perturbed postnatal acquisition and retention of the gut microbiota's viral component in populations at risk for malnutrition.

Authors+Show Affiliations

Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63108; Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, MO 63108; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110; Department of Biological Sciences, Universidad de los Andes, Bogota, 111711 Colombia;Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63108; Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, MO 63108;Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110;Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110;Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110; Department of Community Health, University of Malawi, Blantyre, Malawi;Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110; Department of Pediatrics and Child Healthy, University of Malawi, Blantyre, Malawi;Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63108;Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110;Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110;Department of Biology, San Diego State University, San Diego, CA 92182.Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63108; Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, MO 63108; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110; jgordon@wustl.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Twin Study

Language

eng

PubMed ID

26351661

Citation

Reyes, Alejandro, et al. "Gut DNA Viromes of Malawian Twins Discordant for Severe Acute Malnutrition." Proceedings of the National Academy of Sciences of the United States of America, vol. 112, no. 38, 2015, pp. 11941-6.
Reyes A, Blanton LV, Cao S, et al. Gut DNA viromes of Malawian twins discordant for severe acute malnutrition. Proc Natl Acad Sci USA. 2015;112(38):11941-6.
Reyes, A., Blanton, L. V., Cao, S., Zhao, G., Manary, M., Trehan, I., ... Gordon, J. I. (2015). Gut DNA viromes of Malawian twins discordant for severe acute malnutrition. Proceedings of the National Academy of Sciences of the United States of America, 112(38), pp. 11941-6. doi:10.1073/pnas.1514285112.
Reyes A, et al. Gut DNA Viromes of Malawian Twins Discordant for Severe Acute Malnutrition. Proc Natl Acad Sci USA. 2015 Sep 22;112(38):11941-6. PubMed PMID: 26351661.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Gut DNA viromes of Malawian twins discordant for severe acute malnutrition. AU - Reyes,Alejandro, AU - Blanton,Laura V, AU - Cao,Song, AU - Zhao,Guoyan, AU - Manary,Mark, AU - Trehan,Indi, AU - Smith,Michelle I, AU - Wang,David, AU - Virgin,Herbert W, AU - Rohwer,Forest, AU - Gordon,Jeffrey I, Y1 - 2015/09/08/ PY - 2015/9/10/entrez PY - 2015/9/10/pubmed PY - 2015/12/22/medline KW - age/disease-discriminatory phage and eukaryotic viruses KW - assembly of the human gut DNA virome KW - childhood malnutrition KW - epidemiology KW - gnotobiotic mice SP - 11941 EP - 6 JF - Proceedings of the National Academy of Sciences of the United States of America JO - Proc. Natl. Acad. Sci. U.S.A. VL - 112 IS - 38 N2 - The bacterial component of the human gut microbiota undergoes a definable program of postnatal development. Evidence is accumulating that this program is disrupted in children with severe acute malnutrition (SAM) and that their persistent gut microbiota immaturity, which is not durably repaired with current ready-to-use therapeutic food (RUTF) interventions, is causally related to disease pathogenesis. To further characterize gut microbial community development in healthy versus malnourished infants/children, we performed a time-series metagenomic study of DNA isolated from virus-like particles (VLPs) recovered from fecal samples collected during the first 30 mo of postnatal life from eight pairs of mono- and dizygotic Malawian twins concordant for healthy growth and 12 twin pairs discordant for SAM. Both members of discordant pairs were sampled just before, during, and after treatment with a peanut-based RUTF. Using Random Forests and a dataset of 17,676 viral contigs assembled from shotgun sequencing reads of VLP DNAs, we identified viruses that distinguish different stages in the assembly of the gut microbiota in the concordant healthy twin pairs. This developmental program is impaired in both members of SAM discordant pairs and not repaired with RUTF. Phage plus members of the Anelloviridae and Circoviridae families of eukaryotic viruses discriminate discordant from concordant healthy pairs. These results disclose that apparently healthy cotwins in discordant pairs have viromes associated with, although not necessarily mediators, of SAM; as such, they provide a human model for delineating normal versus perturbed postnatal acquisition and retention of the gut microbiota's viral component in populations at risk for malnutrition. SN - 1091-6490 UR - https://www.unboundmedicine.com/medline/citation/26351661/Gut_DNA_viromes_of_Malawian_twins_discordant_for_severe_acute_malnutrition_ L2 - http://www.pnas.org/cgi/pmidlookup?view=long&pmid=26351661 DB - PRIME DP - Unbound Medicine ER -