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Title: Effects of microbiota-directed foods in gnotobiotic animals and undernourished children

Abstract

To examine the contributions of impaired gut microbial community development to childhood undernutrition, we combined metabolomic and proteomic analyses of plasma samples with metagenomic analyses of fecal samples to characterize the biological state of Bangladeshi children with severe acute malnutrition (SAM) as they transitioned, after standard treatment, to moderate acute malnutrition (MAM) with persistent microbiota immaturity. Host and microbial effects of microbiota-directed complementary food (MDCF) prototypes targeting weaning-phase bacterial taxa underrepresented in SAM and MAM microbiota were characterized in gnotobiotic mice and gnotobiotic piglets colonized with age- and growth-discriminatory bacteria. A randomized, double-blind controlled feeding study identified a lead MDCF that changes the abundances of targeted bacteria and increases plasma biomarkers and mediators of growth, bone formation, neurodevelopment, and immune function in children with MAM.

Authors:
 [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1];  [2]; ORCiD logo [3]; ORCiD logo [4];  [5];  [5];  [5] more »;  [1];  [1];  [6];  [6];  [6];  [7];  [8];  [8];  [8];  [8];  [8];  [8];  [8];  [8];  [1];  [8];  [1] « less
  1. Washington Univ., St. Louis, MO (United States)
  2. Aix-Marseille Univ., and CNRS/IN2P3, Marseille (France); King Abdulaziz Univ., Jeddah (Saudi Arabia)
  3. Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
  4. {Bob} L. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
  5. Duke Univ., Durham, NC (United States)
  6. Sanford Burnham Prebys Medical Discovery Inst., La Jolla, CA (United States); Russian Academy of Sciences (RAS), Moscow (Russian Federation)
  7. Sanford Burnham Prebys Medical Discovery Inst., La Jolla, CA (United States)
  8. International Centre for Diarrhoeal Disease Research (Bangladesh)
Publication Date:
Research Org.:
Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1546507
Grant/Contract Number:  
AC05-00OR22725
Resource Type:
Accepted Manuscript
Journal Name:
Science
Additional Journal Information:
Journal Volume: 365; Journal Issue: 6449; Journal ID: ISSN 0036-8075
Publisher:
AAAS
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Gehrig, Jeanette, Venkatesh, Siddarth, Chang, Hao-Wei, Hibberd, Matthew C., Kung, Vanderlene, Cheng, Jiye, Chen, Robert, Subramanian, Sathish, Cowardin, Carrie, Meier, Martin, O'Donnell, David, Talcott, Michael, Spears, Larry, Semenkovich, Clay, Henrissat, Bernard, Giannone, Richard J., Hettich, Robert, Ilkayeva, Olga, Muehlbauer, Michael, Newgard, Christopher, Sawyer, Christopher, Head, Richard, Rodionov, Dmitry A., Arzamasov, Aleksandr, Leyn, Semen, Osterman, Andrei L., Hossain, Md Iqbal, Islam, Munirul, Choudhury, Nuzhat, Sarker, Shafiqul, Huq, Sayeeda, Mahmud, Imteaz, Mostafa, Ishita, Mahfuz, Mustafa, Barratt, Michael J., Ahmed, Tahmeed, and Gordon, Jeffrey I. Effects of microbiota-directed foods in gnotobiotic animals and undernourished children. United States: N. p., 2019. Web. doi:10.1126/science.aau4732.
Gehrig, Jeanette, Venkatesh, Siddarth, Chang, Hao-Wei, Hibberd, Matthew C., Kung, Vanderlene, Cheng, Jiye, Chen, Robert, Subramanian, Sathish, Cowardin, Carrie, Meier, Martin, O'Donnell, David, Talcott, Michael, Spears, Larry, Semenkovich, Clay, Henrissat, Bernard, Giannone, Richard J., Hettich, Robert, Ilkayeva, Olga, Muehlbauer, Michael, Newgard, Christopher, Sawyer, Christopher, Head, Richard, Rodionov, Dmitry A., Arzamasov, Aleksandr, Leyn, Semen, Osterman, Andrei L., Hossain, Md Iqbal, Islam, Munirul, Choudhury, Nuzhat, Sarker, Shafiqul, Huq, Sayeeda, Mahmud, Imteaz, Mostafa, Ishita, Mahfuz, Mustafa, Barratt, Michael J., Ahmed, Tahmeed, & Gordon, Jeffrey I. Effects of microbiota-directed foods in gnotobiotic animals and undernourished children. United States. doi:10.1126/science.aau4732.
Gehrig, Jeanette, Venkatesh, Siddarth, Chang, Hao-Wei, Hibberd, Matthew C., Kung, Vanderlene, Cheng, Jiye, Chen, Robert, Subramanian, Sathish, Cowardin, Carrie, Meier, Martin, O'Donnell, David, Talcott, Michael, Spears, Larry, Semenkovich, Clay, Henrissat, Bernard, Giannone, Richard J., Hettich, Robert, Ilkayeva, Olga, Muehlbauer, Michael, Newgard, Christopher, Sawyer, Christopher, Head, Richard, Rodionov, Dmitry A., Arzamasov, Aleksandr, Leyn, Semen, Osterman, Andrei L., Hossain, Md Iqbal, Islam, Munirul, Choudhury, Nuzhat, Sarker, Shafiqul, Huq, Sayeeda, Mahmud, Imteaz, Mostafa, Ishita, Mahfuz, Mustafa, Barratt, Michael J., Ahmed, Tahmeed, and Gordon, Jeffrey I. Fri . "Effects of microbiota-directed foods in gnotobiotic animals and undernourished children". United States. doi:10.1126/science.aau4732. https://www.osti.gov/servlets/purl/1546507.
@article{osti_1546507,
title = {Effects of microbiota-directed foods in gnotobiotic animals and undernourished children},
author = {Gehrig, Jeanette and Venkatesh, Siddarth and Chang, Hao-Wei and Hibberd, Matthew C. and Kung, Vanderlene and Cheng, Jiye and Chen, Robert and Subramanian, Sathish and Cowardin, Carrie and Meier, Martin and O'Donnell, David and Talcott, Michael and Spears, Larry and Semenkovich, Clay and Henrissat, Bernard and Giannone, Richard J. and Hettich, Robert and Ilkayeva, Olga and Muehlbauer, Michael and Newgard, Christopher and Sawyer, Christopher and Head, Richard and Rodionov, Dmitry A. and Arzamasov, Aleksandr and Leyn, Semen and Osterman, Andrei L. and Hossain, Md Iqbal and Islam, Munirul and Choudhury, Nuzhat and Sarker, Shafiqul and Huq, Sayeeda and Mahmud, Imteaz and Mostafa, Ishita and Mahfuz, Mustafa and Barratt, Michael J. and Ahmed, Tahmeed and Gordon, Jeffrey I.},
abstractNote = {To examine the contributions of impaired gut microbial community development to childhood undernutrition, we combined metabolomic and proteomic analyses of plasma samples with metagenomic analyses of fecal samples to characterize the biological state of Bangladeshi children with severe acute malnutrition (SAM) as they transitioned, after standard treatment, to moderate acute malnutrition (MAM) with persistent microbiota immaturity. Host and microbial effects of microbiota-directed complementary food (MDCF) prototypes targeting weaning-phase bacterial taxa underrepresented in SAM and MAM microbiota were characterized in gnotobiotic mice and gnotobiotic piglets colonized with age- and growth-discriminatory bacteria. A randomized, double-blind controlled feeding study identified a lead MDCF that changes the abundances of targeted bacteria and increases plasma biomarkers and mediators of growth, bone formation, neurodevelopment, and immune function in children with MAM.},
doi = {10.1126/science.aau4732},
journal = {Science},
number = 6449,
volume = 365,
place = {United States},
year = {2019},
month = {7}
}

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Figures / Tables:

Fig. 1 Fig. 1: Longitudinal study of Bangladeshi children with SAM treated with therapeutic foods. (A) Study design. (B) Anthropometry and MAZ scores. Gray bars represent the three time points at which blood samples were collected. (C) Summary of MAZ scores for children with SAM (WHZ < –3; n = 96 fecalmore » samples) and subsequently (post-SAM) MAM (WHZ > –3 and <–2; n = 151 fecal samples), plus healthy children aged 6 to 24 months living in the same area in which the SAM study was conducted (n = 450 fecal samples). Mean values for WHZ, WAZ, HAZ, and MAZ ± SEM are plotted on the x axes of (B) and (C). ****P < 0.0001 (one-way ANOVA followed by Tukey’s multiple comparisons test).« less

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    Works referencing / citing this record:

    Annual Research Review: Critical windows – the microbiota–gut–brain axis in neurocognitive development
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    • Cowan, Caitlin S. M.; Dinan, Timothy G.; Cryan, John F.
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    Problems with the concept of gut microbiota dysbiosis
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    Understanding the mother-breastmilk-infant “triad”
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    Annual Research Review: Critical windows – the microbiota–gut–brain axis in neurocognitive development
    journal, November 2019

    • Cowan, Caitlin S. M.; Dinan, Timothy G.; Cryan, John F.
    • Journal of Child Psychology and Psychiatry
    • DOI: 10.1111/jcpp.13156

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