title: Functional characterization of IgA-targeted bacterial taxa from undernourished Malawian children that produce diet-dependent enteropathy.
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.affiliation: 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.
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Kau
authors.affiliation: Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63108, USA.
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Planer
authors.affiliation: Department of Medicine, Division of Infectious Diseases and International Health, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Sindhuja
authors.initials: S
authors.lastname: Rao
authors.affiliation: Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63108, USA.
authors.forename: Tanya
authors.initials: T
authors.lastname: Yatsunenko
authors.affiliation: 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.
authors.forename: Indi
authors.initials: I
authors.lastname: Trehan
authors.affiliation: 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.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Manary
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Ta-Chiang
authors.initials: TC
authors.lastname: Liu
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Thaddeus S
authors.initials: TS
authors.lastname: Stappenbeck
authors.affiliation: Department of Community Health, College of Medicine, University of Malawi, Chichiri, Blantyre 3, Malawi.
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Maleta
authors.affiliation: Department for International Health, University of Tampere School of Medicine, Tampere 33014, Finland.
authors.forename: Per
authors.initials: P
authors.lastname: Ashorn
authors.affiliation: Department of Nutrition, and Program in International and Community Nutrition, University of California, Davis, Davis, CA 95616, USA.
authors.forename: Kathryn G
authors.initials: KG
authors.lastname: Dewey
authors.affiliation: Department of Medicine, Division of Infectious Diseases and International Health, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
authors.forename: Eric R
authors.initials: ER
authors.lastname: Houpt
authors.affiliation: Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Chyi-Song
authors.initials: CS
authors.lastname: Hsieh
authors.affiliation: Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63108, USA. jgordon@wustl.edu.
authors.forename: Jeffrey I
authors.initials: JI
authors.lastname: Gordon
mesh_terms: D000818:Animals; D001419:Bacteria / Q000145:classification*; D002648:Child; D015331:Cohort Studies; D004032:Diet; D005243:Feces / Q000382:microbiology; D005767:Gastrointestinal Diseases / Q000382:microbiology*; D041981:Gastrointestinal Tract / Q000382:microbiology / Q000473:pathology; D005856:Germ-Free Life; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism*; D007223:Infant; D007732:Kwashiorkor / Q000382:microbiology*; D008295:Malawi; D008810:Mice, Inbred C57BL; D059013:Microbial Consortia; D010641:Phenotype
chemical_list: D007070:Immunoglobulin A