Gut Microbiomes of Malawian Twin Pairs Discordant for Kwashiorkor

被引:847
作者
Smith, Michelle I. [1 ]
Yatsunenko, Tanya [1 ]
Manary, Mark J. [2 ,3 ,4 ,5 ]
Trehan, Indi [2 ,3 ,4 ]
Mkakosya, Rajhab [6 ]
Cheng, Jiye [1 ]
Kau, Andrew L. [1 ]
Rich, Stephen S. [7 ]
Concannon, Patrick [7 ]
Mychaleckyj, Josyf C. [7 ]
Liu, Jie [8 ]
Houpt, Eric [8 ]
Li, Jia V. [9 ]
Holmes, Elaine [9 ]
Nicholson, Jeremy [9 ]
Knights, Dan [10 ,11 ]
Ursell, Luke K. [12 ]
Knight, Rob [10 ,11 ,12 ,13 ]
Gordon, Jeffrey I. [1 ]
机构
[1] Washington Univ, Ctr Genome Sci & Syst Biol, St Louis, MO 63110 USA
[2] Washington Univ, Dept Pediat, St Louis, MO 63110 USA
[3] Univ Malawi, Coll Med, Dept Community Hlth, Blantyre 3, Malawi
[4] Univ Malawi, Coll Med, Dept Pediat & Child Hlth, Blantyre 3, Malawi
[5] Baylor Coll Med, USDA, Childrens Nutr Res Ctr, Houston, TX 77030 USA
[6] Univ Malawi, Coll Med, Dept Microbiol, Blantyre 3, Malawi
[7] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA 22904 USA
[8] Univ Virginia, Div Infect Dis & Internal Hlth, Charlottesville, VA 22908 USA
[9] Univ London Imperial Coll Sci Technol & Med, Fac Med, Dept Surg & Canc, London SW7 2AZ, England
[10] Univ Colorado, Dept Comp Sci, Boulder, CO 80309 USA
[11] Univ Colorado, Biofrontiers Inst, Boulder, CO 80309 USA
[12] Univ Colorado, Dept Chem & Biochem, Boulder, CO 80309 USA
[13] Univ Colorado, Howard Hughes Med Inst, Boulder, CO 80309 USA
基金
比尔及梅琳达.盖茨基金会;
关键词
SERUM AMINO-ACIDS; CHILDREN; FOOD; FERMENTATION; BACTERIA; PLASMA; URINE; PCR;
D O I
10.1126/science.1229000
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Kwashiorkor, an enigmatic form of severe acute malnutrition, is the consequence of inadequate nutrient intake plus additional environmental insults. To investigate the role of the gut microbiome, we studied 317 Malawian twin pairs during the first 3 years of life. During this time, half of the twin pairs remained well nourished, whereas 43% became discordant, and 7% manifested concordance for acute malnutrition. Both children in twin pairs discordant for kwashiorkor were treated with a peanut-based, ready-to-use therapeutic food (RUTF). Time-series metagenomic studies revealed that RUTF produced a transient maturation of metabolic functions in kwashiorkor gut microbiomes that regressed when administration of RUTF was stopped. Previously frozen fecal communities from several discordant pairs were each transplanted into gnotobiotic mice. The combination of Malawian diet and kwashiorkor microbiome produced marked weight loss in recipient mice, accompanied by perturbations in amino acid, carbohydrate, and intermediary metabolism that were only transiently ameliorated with RUTF. These findings implicate the gut microbiome as a causal factor in kwashiorkor.
引用
收藏
页码:548 / 554
页数:7
相关论文
共 36 条
[1]  
Ahmed T, 2009, INDIAN J MED RES, V130, P651
[2]  
[Anonymous], CALORIE DEFICIENCIES
[3]   FREE AMINO ACIDS IN BLOOD PLASMA OF CHILDREN WITH KWASHIORKOR AND MARASMUS [J].
ARROYAVE, G ;
FUNES, CD ;
BEHAR, M ;
WILSON, D .
AMERICAN JOURNAL OF CLINICAL NUTRITION, 1962, 11 (05) :517-+
[4]  
AWWAAD S, 1962, J TROP MED HYG, V65, P179
[5]  
BAKER DH, 1986, PROG FOOD NUTR SCI, V10, P133
[6]   Metabolic profiling, metabolomic and metabonomic procedures for NMR spectroscopy of urine, plasma, serum and tissue extracts [J].
Beckonert, Olaf ;
Keun, Hector C. ;
Ebbels, Timothy M. D. ;
Bundy, Jacob G. ;
Holmes, Elaine ;
Lindon, John C. ;
Nicholson, Jeremy K. .
NATURE PROTOCOLS, 2007, 2 (11) :2692-2703
[7]  
Black RE, 2008, LANCET, V371, P243, DOI [10.1016/S0140-6736(07)61690-0, 10.1016/S0140-6736(13)60937-X]
[8]   Antioxidant supplementation for the prevention of kwashiorkor in Malawian children: randomised, double blind, placebo controlled trial [J].
Ciliberto, H ;
Ciliberto, M ;
Briend, A ;
Ashorn, P ;
Bier, D ;
Manary, M .
BMJ-BRITISH MEDICAL JOURNAL, 2005, 330 (7500) :1109-1111
[9]   Clostridium innocuum Bacteremia in a Patient With Acquired Immunodeficiency Syndrome [J].
Crum-Cianflone, Nancy .
AMERICAN JOURNAL OF THE MEDICAL SCIENCES, 2009, 337 (06) :480-482
[10]   WHO Child Growth Standards based on length/height, weight and age [J].
de Onis, Mercedes ;
Martorell, Reynaldo ;
Garza, Cutberto ;
Lartey, Anna .
ACTA PAEDIATRICA, 2006, 95 :76-85