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

Kau AL, Planer JD, Liu J, Rao S, Yatsunenko T, Trehan I, Manary MJ, Liu TC, Stappenbeck TS, Maleta KM, Ashorn P, Dewey KG, Houpt ER, Hsieh CS, Gordon JI

To gain insights into the interrelationships among childhood undernutrition, the gut microbiota, and gut mu- cosal 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 furt her explained by enteropathogen burden. Gnotobiotic mouse recipients of an IgA + bacterial consortium purified from the gut mi crobiota of undernourished children ex- hibited a diet-dependent enteropathy cha racterized by rapid disruption of the sm all intestinal and colonic epithelial barrier, weight loss, and sepsis that could be prevented by ad ministering two IgA-targeted bacterial species from a healthy microbiota. Dissection of a culture collection o f 11 IgA-targeted strains from an undernourished donor, suf- ficient to transmit these phenotypes, disclosed that Enterobacteriaceae interacted wit h other consortium members to produce enteropathy. These findings indicate that bacterial targets of IgA responses h ave etiologic, diagnostic, and therapeutic implicati ons for childhood undernutrition

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February, 2015




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