Editors' ChoiceMalnutrition

The Gut Microbiome and Malnutrition

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Science Translational Medicine  03 Apr 2013:
Vol. 5, Issue 179, pp. 179ec55
DOI: 10.1126/scitranslmed.3006203

Poor nutrition contributes to more than one-third of all childhood deaths worldwide. Recent evidence suggests that an inadequate response of the host gut microbiome to caloric deficit may be responsible for malnutrition, but this is still under debate. One puzzle is that in the developing world, both malnourished and healthy children coexist in the same family with the same access to calories.

Kwashiorkor or edematous malnutrition is a profound form of severe acute malnutrition with a high fatality rate. In a new study conducted on the fecal microbiomes of 317 monozygotic (MZ) and dizygotic (DZ) twin pairs in Malawi, Smith et al. set out to understand the role of nutritional status in kwashiorkor. The investigators studied the twin pairs for the first 3 years of life, during which time half of the twin pairs remained healthy, whereas 7% became concordant for acute malnutrition, and the remaining 43% became discordant for acute malnutrition. The well-nourished co-twins with similar environmental and dietary exposures in the discordant twin pairs were controls. All of the children in twin pairs discordant for acute malnutrition were treated with a peanut-based standard ready-to-use therapeutic food (RUTF), and changes in their gut microbiomes were studied before and after RUTF treatment.

Metagenomic analyses of microbiomes from 9 same-gender healthy twin pairs and 13 same-gender twin pairs discordant for kwashiorkor revealed the expected maturation of the gut microbiota with development in the healthy control twin pairs and in the healthy co-twin of the discordant twin pairs fed a traditional Malawian diet. However, normal maturation of the gut microbiota was not observed in those co-twins with kwashiorkor, implicating a dysfunctional gut microbiome in malnutrition. When the children were fed RUTF, there was transient maturation of the gut microbiome in the kwashiorkor co-twins, but this regressed once RUTF treatment was halted. When frozen fecal microbiomes from three discordant twin pairs were transplanted into gnotobiotic mice fed a regular Malawian diet, the researchers noted marked weight loss and disturbances in metabolic profiles in the mice transplanted with microbiomes from the co-twins with kwashiorkor but not from the healthier co-twins. When the anorexic transplanted mice were fed RUTF, the investigators noted weight gain and improved metabolic profiles as they had observed in the kwashiorkor co-twins fed RUTF.This study implicates the gut microbiome in the pathogenesis of kwashiorkor and explores the interrelationships among the host microbiota, diet, and metabolic responses after RUTF supplementation, offering greater insights into the effective management of malnutrition.

M. I. Smith et al., Gut microbiomes of Malawian twin pairs discordant for kwashiorkor. Science 339, 548–554 (2013). [Abstract]

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