TY - JOUR
T1 - Functional characterization of IgA-targeted bacterial taxa from undernourished Malawian children that produce diet-dependent enteropathy
AU - Kau, Andrew L.
AU - Planer, Joseph D.
AU - Liu, Jie
AU - Rao, Sindhuja
AU - Yatsunenko, Tanya
AU - Trehan, Indi
AU - Manary, Mark J.
AU - Liu, Ta Chiang
AU - Stappenbeck, Thaddeus
AU - Maleta, Kenneth M.
AU - Ashorn, Per
AU - Dewey, Kathryn G.
AU - Houpt, Eric R.
AU - Hsieh, Chyi Song
AU - Gordon, Jeffrey I.
N1 - Publisher Copyright:
Copyright © 2015, American Association for the Advancement of Science.
PY - 2015/2/25
Y1 - 2015/2/25
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84991929179&partnerID=8YFLogxK
U2 - 10.1126/scitranslmed.aaa4877
DO - 10.1126/scitranslmed.aaa4877
M3 - Article
C2 - 25717097
AN - SCOPUS:84991929179
SN - 1946-6234
VL - 7
SP - 276ra24
JO - Science translational medicine
JF - Science translational medicine
IS - 276
ER -