Gut microbiomes of Malawian twin pairs discordant for kwashiorkor.
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.
Center for Genome Sciences and Systems Biology, Washington University in St. Louis, St. Louis, MO 63110, USA.
Michelle I
MI
Smith
Tanya
T
Yatsunenko
Mark J
MJ
Manary
Indi
I
Trehan
Rajhab
R
Mkakosya
Jiye
J
Cheng
Andrew L
AL
Kau
Stephen S
SS
Rich
Patrick
P
Concannon
Josyf C
JC
Mychaleckyj
Jie
J
Liu
Eric
E
Houpt
Jia V
JV
Li
Elaine
E
Holmes
Jeremy
J
Nicholson
Dan
D
Knights
Luke K
LK
Ursell
Rob
R
Knight
Jeffrey I
JI
Gordon
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D010367:Arachis; D050260:Carbohydrate Metabolism; D002675:Child, Preschool; D004200:Diseases in Twins / Q000382:microbiology*; D005243:Feces / Q000382:microbiology; D005260:Female; D041981:Gastrointestinal Tract / Q000382:microbiology*; D005856:Germ-Free Life; D006801:Humans; D007223:Infant; D007732:Kwashiorkor / Q000178:diet therapy / Q000453:epidemiology / Q000382:microbiology*; D008137:Longitudinal Studies; D008295:Malawi / Q000453:epidemiology; D008297:Male; D054892:Metagenome; D051379:Mice; D008810:Mice, Inbred C57BL
D000596:Amino Acids