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Functional characterization of IgA-targeted bacterial taxa from undernourished Malawian children that produce diet-dependent enteropathy.
Sci Transl Med 2015; 7(276):276ra24ST

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.

Authors+Show Affiliations

Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63108, USA. Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63108, USA.Department of Medicine, Division of Infectious Diseases and International Health, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63108, USA.Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110, USA. Department of Paediatrics and Child Health, College of Medicine, University of Malawi, Chichiri, Blantyre 3, Malawi.Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110, USA. Department of Community Health, College of Medicine, University of Malawi, Chichiri, Blantyre 3, Malawi.Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.Department of Community Health, College of Medicine, University of Malawi, Chichiri, Blantyre 3, Malawi.Department for International Health, University of Tampere School of Medicine, Tampere 33014, Finland.Department of Nutrition, and Program in International and Community Nutrition, University of California, Davis, Davis, CA 95616, USA.Department of Medicine, Division of Infectious Diseases and International Health, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63108, USA. jgordon@wustl.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Twin Study

Language

eng

PubMed ID

25717097

Citation

Kau, Andrew L., et al. "Functional Characterization of IgA-targeted Bacterial Taxa From Undernourished Malawian Children That Produce Diet-dependent Enteropathy." Science Translational Medicine, vol. 7, no. 276, 2015, pp. 276ra24.
Kau AL, Planer JD, Liu J, et al. Functional characterization of IgA-targeted bacterial taxa from undernourished Malawian children that produce diet-dependent enteropathy. Sci Transl Med. 2015;7(276):276ra24.
Kau, A. L., Planer, J. D., Liu, J., Rao, S., Yatsunenko, T., Trehan, I., ... Gordon, J. I. (2015). Functional characterization of IgA-targeted bacterial taxa from undernourished Malawian children that produce diet-dependent enteropathy. Science Translational Medicine, 7(276), pp. 276ra24. doi:10.1126/scitranslmed.aaa4877.
Kau AL, et al. Functional Characterization of IgA-targeted Bacterial Taxa From Undernourished Malawian Children That Produce Diet-dependent Enteropathy. Sci Transl Med. 2015 Feb 25;7(276):276ra24. PubMed PMID: 25717097.
* Article titles in AMA citation format should be in sentence-case
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 S, AU - Maleta,Kenneth M, AU - Ashorn,Per, AU - Dewey,Kathryn G, AU - Houpt,Eric R, AU - Hsieh,Chyi-Song, AU - Gordon,Jeffrey I, PY - 2015/2/27/entrez PY - 2015/2/27/pubmed PY - 2015/11/17/medline SP - 276ra24 EP - 276ra24 JF - Science translational medicine JO - Sci Transl Med VL - 7 IS - 276 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. SN - 1946-6242 UR - https://www.unboundmedicine.com/medline/citation/25717097/Functional_characterization_of_IgA_targeted_bacterial_taxa_from_undernourished_Malawian_children_that_produce_diet_dependent_enteropathy_ L2 - http://stm.sciencemag.org/cgi/pmidlookup?view=short&pmid=25717097 DB - PRIME DP - Unbound Medicine ER -