@article{2281803b26744f319af3003481b9af17,
title = "Gut bacteria that prevent growth impairments transmitted by microbiota from malnourished children",
abstract = "Undernourished children exhibit impaired development of their gut microbiota. Transplanting microbiota from 6- and 18-month-old healthy or undernourished Malawian donors into young germ-free mice that were fed a Malawian diet revealed that immature microbiota from undernourished infants and children transmit impaired growth phenotypes. The representation of several age-discriminatory taxa in recipient animals correlated with lean body mass gain; liver, muscle, and brain metabolism; and bone morphology. Mice were cohoused shortly after receiving microbiota from healthy or severely stunted and underweight infants; age- and growth-discriminatory taxa from the microbiota of the former were able to invade that of the latter, which prevented growth impairments in recipient animals. Adding two invasive species, Ruminococcus gnavus and Clostridium symbiosum, to the microbiota from undernourished donors also ameliorated growth and metabolic abnormalities in recipient animals. These results provide evidence that microbiota immaturity is causally related to undernutrition and reveal potential therapeutic targets and agents.",
author = "Blanton, {Laura V.} and Charbonneau, {Mark R.} and Tarek Salih and Barratt, {Michael J.} and Siddarth Venkatesh and Olga Ilkaveya and Sathish Subramanian and Manary, {Mark J.} and Indi Trehan and Jorgensen, {Josh M.} and Fan, {Yue Mei} and Bernard Henrissat and Leyn, {Semen A.} and Rodionov, {Dmitry A.} and Osterman, {Andrei L.} and Maleta, {Kenneth M.} and Newgard, {Christopher B.} and Per Ashorn and Dewey, {Kathryn G.} and Gordon, {Jeffrey I.}",
note = "Funding Information: We are indebted to the parents and children from Malawi for their participation in this study. We thank S. Wagoner, D. O''Donnell, M. Karlsson, and J. Serugo for their assistance with gnotobiotic mouse husbandry; D. Leib and M. Silva for their assistance with bone morphology assays; J. Guruge for help with anaerobic microbiology; B. Dankenbring for assistance with maintenance of the biospecimen repository; and M. Meier, S. Deng, and J. Hoisington-Lopez for their contribution to various facets of the DNA sequencing pipeline. This work was supported by the Bill and Melinda Gates Foundation and the NIH (grant DK30292). Additional funding was provided by the Office of Health, Infectious Diseases and Nutrition, Bureau for Global Health, U.S. Agency for International Development under the terms of cooperative agreement no. AID-OAA-A-12-00005, through the Food and Nutrition Technical Assistance III Project managed by FHI 360. Data management and statistical analysis for the iLiNS-DYAD-M clinical study were also funded by the Academy of Finland (grant 252075) and the Medical Research Fund of Tampere University Hospital (grant 9M004). Micro-CT analysis was performed in the Washington University Musculoskeletal Research Center, which is supported by NIH grant P30 AR057235. L.V.B. received stipend support from NIH predoctoral training grants NIH T32 AI007172 and T32 GM007067 and from the Lucille P. Markey Special Emphasis Pathway in Human Pathobiology. D.A.R. and S.A.L. were supported by the Russian Science Foundation (grant 14-14-00289). Collection of the human specimens included in this study was approved by the University of Malawi College of Medicine Research Ethics Committee. Specimens were provided to Washington University in St. Louis under a materials transfer agreement (MTA) between the University of Malawi and Washington University, and their collection and use for this study was approved by the Washington University Human Research Protection Office (Federalwide Assurance no. FWA00002284). 16S rRNA sequences, generated from fecal samples in raw format before postprocessing and data analysis, and shotgun sequencing data sets, generated from the R. gnavus TS8243C and C. symbiosum TS8243C genomes, have been deposited in the European Nucleotide Archive under accession number PRJEB9853. J.I.G. is a cofounder of Matatu, a company characterizing the role of diet-by-microbiota interactions in animal health. A.L.O. is an adjunct vice president for research for Buffalo BioLabs. L.V.B., M.R.C., and J.I.G. designed the gnotobiotic mouse studies; L.V.B. and M.R.C. performed the experiments with gnotobiotic animals; I.T. and M.J.M. designed and implemented the clinical monitoring and sampling for the twin study and participated in patient recruitment, sample collection and preservation, and/or clinical evaluations; K.M.M., Y.F., J.M.J., K.G.D., and P.A. designed and oversaw the clinical studies, sample collection and processing, and/or clinical monitoring and evaluations in the iLiNS-DYAD-M study; L.V.B. generated the 16S rRNA data; L.V.B., M.R.C., S.V., and O.I. generated the metabolomics data; T.S. and L.V.B. cultured bacterial isolates; B.H., D.A.R., S.A.L., and A.L.O. performed metabolic reconstructions of the R. gnavus and C. symbiosum genomes; L.V.B., M.R.C., M.J.B., S.S., C.B.N., and J.I.G. analyzed the data; and L.V.B. and J.I.G. wrote the paper.",
year = "2016",
month = feb,
day = "19",
doi = "10.1126/science.aad3311",
language = "English",
volume = "351",
journal = "Science",
issn = "0036-8075",
number = "6275",
}