Functional characterization of IgA-targeted bacterial taxa from undernourished Malawian children that produce diet-dependent enteropathy

Andrew L. Kau, Joseph D. Planer, Jie Liu, Sindhuja Rao, Tanya Yatsunenko, Indi Trehan, Mark J. Manary, Ta Chiang Liu, Thaddeus Stappenbeck, Kenneth M. Maleta, Per Ashorn, Kathryn G. Dewey, Eric R. Houpt, Chyi Song Hsieh, Jeffrey I. Gordon

Research output: Contribution to journalArticlepeer-review

224 Scopus citations

Abstract

To gain insights into the interrelationships among childhood undernutrition, the gut microbiota, and gut mucosal immune/barrier function, we purified bacterial strains targeted by immunoglobulin A (IgA) from the fecal microbiota of two cohorts of Malawian infants and children. IgA responses to several bacterial taxa, including Enterobacteriaceae, correlated with anthropometric measurements of nutritional status in longitudinal studies. The relationship between IgA responses and growth was further explained by enteropathogen burden. Gnotobiotic mouse recipients of an IgA(+) bacterial consortium purified from the gut microbiota of undernourished children exhibited a diet-dependent enteropathy characterized by rapid disruption of the small intestinal and colonic epithelial barrier, weight loss, and sepsis that could be prevented by administering two IgA-targeted bacterial species from a healthy microbiota. Dissection of a culture collection of 11 IgA-targeted strains from an undernourished donor, sufficient to transmit these phenotypes, disclosed that Enterobacteriaceae interacted with other consortium members to produce enteropathy. These findings indicate that bacterial targets of IgA responses have etiologic, diagnostic, and therapeutic implications for childhood undernutrition.

Original languageEnglish
Pages (from-to)276ra24
JournalScience translational medicine
Volume7
Issue number276
DOIs
StatePublished - Feb 25 2015

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