Format

Send to

Choose Destination
Sci Transl Med. 2015 Feb 25;7(276):276ra24. doi: 10.1126/scitranslmed.aaa4877.

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

Author information

1
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.
2
Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63108, USA.
3
Department of Medicine, Division of Infectious Diseases and International Health, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
4
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
5
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.
6
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.
7
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
8
Department of Community Health, College of Medicine, University of Malawi, Chichiri, Blantyre 3, Malawi.
9
Department for International Health, University of Tampere School of Medicine, Tampere 33014, Finland.
10
Department of Nutrition, and Program in International and Community Nutrition, University of California, Davis, Davis, CA 95616, USA.
11
Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63108, USA. jgordon@wustl.edu.

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.

PMID:
25717097
PMCID:
PMC4423598
DOI:
10.1126/scitranslmed.aaa4877
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center