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

Jeanette L Gehrig; Siddarth Venkatesh; Hao-Wei Chang; Matthew C Hibberd; Vanderlene L Kung; Jiye Cheng; Robert Y Chen; Sathish Subramanian; Carrie A Cowardin; Martin F Meier; David O'Donnell; Michael Talcott; Larry D Spears; Clay F Semenkovich; Bernard Henrissat; Richard J Giannone; Robert L Hettich; Olga Ilkayeva; Michael Muehlbauer; Christopher B Newgard; Christopher Sawyer; Richard D Head; Dmitry A Rodionov; Aleksandr A Arzamasov; Semen A Leyn; Andrei L Osterman; Md Iqbal Hossain; Munirul Islam; Nuzhat Choudhury; Shafiqul Alam Sarker; Sayeeda Huq; Imteaz Mahmud; Ishita Mostafa; Mustafa Mahfuz; Michael J Barratt; Tahmeed Ahmed; Jeffrey I Gordon

doi:10.1126/science.aau4732

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

Science. 2019 Jul 12;365(6449):eaau4732. doi: 10.1126/science.aau4732.

Authors

Jeanette L Gehrig^#^{1

2}, Siddarth Venkatesh^#^{1

2}, Hao-Wei Chang^#^{1

2}, Matthew C Hibberd^{1

2}, Vanderlene L Kung^{1

2

3}, Jiye Cheng^{1

2}, Robert Y Chen^{1

2}, Sathish Subramanian^{1

2}, Carrie A Cowardin^{1

2}, Martin F Meier^{1

2}, David O'Donnell^{1

2}, Michael Talcott⁴, Larry D Spears⁵, Clay F Semenkovich⁵, Bernard Henrissat^{6

7}, Richard J Giannone⁸, Robert L Hettich⁸, Olga Ilkayeva^{9

10}, Michael Muehlbauer^{9

10}, Christopher B Newgard^{9

10

11

12}, Christopher Sawyer^{13

14}, Richard D Head^{13

14}, Dmitry A Rodionov^{15

16}, Aleksandr A Arzamasov^{15

16}, Semen A Leyn^{15

16}, Andrei L Osterman¹⁶, Md Iqbal Hossain¹⁷, Munirul Islam¹⁷, Nuzhat Choudhury¹⁷, Shafiqul Alam Sarker¹⁷, Sayeeda Huq¹⁷, Imteaz Mahmud¹⁷, Ishita Mostafa¹⁷, Mustafa Mahfuz¹⁷, Michael J Barratt^{1

2}, Tahmeed Ahmed¹⁷, Jeffrey I Gordon^{18

2}

Affiliations

¹ Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63110, USA.
² Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, MO 63110, USA.
³ Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
⁴ Division of Comparative Medicine, Washington University, St. Louis, MO 63110, USA.
⁵ Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
⁶ Architecture et Fonction des Macromolécules Biologiques, Centre National de la Recherche Scientifique and Aix-Marseille Université, 13288 Marseille cedex 9, France.
⁷ Department of Biological Sciences, King Abdulaziz University, Jeddah, Saudi Arabia.
⁸ Chemical Sciences Division, Oak Ridge National Laboratory, Oak Ridge, TN 37830, USA.
⁹ Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, NC 27710, USA.
¹⁰ Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC 27710, USA.
¹¹ Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.
¹² Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
¹³ Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110, USA.
¹⁴ Genome Technology Access Center, Washington University School of Medicine, St. Louis, MO 63110, USA.
¹⁵ A. A. Kharkevich Institute for Information Transmission Problems, Russian Academy of Sciences, Moscow 127994, Russia.
¹⁶ Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
¹⁷ International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka 1212, Bangladesh.
¹⁸ Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63110, USA. jgordon@wustl.edu.

^# Contributed equally.

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.

Publication types

Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Bangladesh
Blood Proteins / analysis
Child Nutrition Disorders / diet therapy*
Child Nutrition Disorders / metabolism
Child Nutrition Disorders / microbiology*
Child, Preschool
Gastrointestinal Microbiome*
Germ-Free Life*
Host Microbial Interactions*
Humans
Infant
Infant Nutritional Physiological Phenomena*

Substances

Blood Proteins

Abstract

Publication types

MeSH terms

Substances

Grants and funding