Gut microbiomes of Malawian twin pairs discordant for kwashiorkor

Michelle I. Smith, Tanya Yatsunenko, Mark J. Manary, Indi Trehan, Rajhab Mkakosya, Jiye Cheng, Andrew L. Kau, Stephen S. Rich, Patrick Concannon, Josyf C. Mychaleckyj, Jie Liu, Eric Houpt, Jia V. Li, Elaine Holmes, Jeremy Nicholson, Dan Knights, Luke K. Ursell, Rob Knight, Jeffrey I. Gordon

Research output: Contribution to journalArticle

661 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)548-554
Number of pages7
JournalScience
Volume339
Issue number6119
DOIs
StatePublished - Feb 1 2013

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