Diarrhea in young children from low-income countries leads to large-scale alterations in intestinal microbiota composition

• Type of Material: Article
• Authors: Mihai Pop, University of Maryland; Alan W Walker, Wellcome Trust Sanger Institute; Joseph Paulson, University of Maryland; Brianna Lindsay, University of Maryland; Martin Antonio, Medical Research Council Unit; M Anowar Hossain, International Centre for Diarrhoeal Disease Research; Joseph Oundo, Kenya Medical Research Institute; Boubou Tamboura, Center for Vaccine Development, Mali; Volker Mai, University of Florida; Irina Astrovskaya, University of Maryland; Hector Corrada Bravo, University of Maryland; Richard Rance, Wellcome Trust Sanger Institute; Mark Stares, Wellcome Trust Sanger Institute; Myron M Levine, University of Maryland; Sandra Panchalingam, University of Maryland; Karen Kotloff, University of Maryland; Usman N Ikumapayi, Medical Research Council Unit; Chinelo Ebruke, Medical Research Council Unit; Mitchell Adeyemi, Medical Research Council Unit; Dilruba Ahmed, International Centre for Diarrhoeal Disease Research; Firoz Ahmed, International Centre for Diarrhoeal Disease Research; Meer Taifur Alam, International Centre for Diarrhoeal Disease Research; Ruhul Amin, International Centre for Diarrhoeal Disease Research; Sabbir Siddiqui, International Centre for Diarrhoeal Disease Research; John B Ochieng, Kenya Medical Research Institute; Emmanuel Ouma, Kenya Medical Research Institute; Jane Juma, Kenya Medical Research Institute; Euince Mailu, Kenya Medical Research Institute; Richard Omore, Kenya Medical Research Institute; J Glenn Morris, University of Florida; Robert F Breiman, Emory University; Debasish Saha, Medical Research Council Unit; Julian Parkhill, Wellcome Trust Sanger Institute; James P Nataro, University of Virginia; O Colin Stine, University of Maryland
• Language: English
• Date: 2014-06-27
• Publisher: BioMed Central
• Publication Version: Final Published Version
• Copyright Statement: © 2014 Pop et al.; licensee BioMed Central Ltd.
• License: Creative Commons Attribution 2.0 Generic
• Final Published Version (URL): http://genomebiology.com/2014/15/6/R76
• Title of Journal or Parent Work: Genome Biology
• ISSN: 1465-6906
• Volume: 15
• Issue: 6
• Start Page: R76
• End Page: R76
• Grant/Funding Information: This work was funded in part by the William and Melinda Gates Foundation, award 42917 to JPN and OCS; US National Institutes of Health grants 5R01HG005220 to HCB, 5R01HG004885 to MP; US National Science Foundation Graduate Research Fellowship award DGE0750616 to JNP; AWW and JP are funded by The Wellcome Trust (Grant No. WT098051).
• Research Categories: Health Sciences, Public Health

Abstract

Background Diarrheal diseases continue to contribute significantly to morbidity and mortality in infants and young children in developing countries. There is an urgent need to better understand the contributions of novel, potentially uncultured, diarrheal pathogens to severe diarrheal disease, as well as distortions in normal gut microbiota composition that might facilitate severe disease. Results We use high throughput 16S rRNA gene sequencing to compare fecal microbiota composition in children under five years of age who have been diagnosed with moderate to severe diarrhea (MSD) with the microbiota from diarrhea-free controls. Our study includes 992 children from four low-income countries in West and East Africa, and Southeast Asia. Known pathogens, as well as bacteria currently not considered as important diarrhea-causing pathogens, are positively associated with MSD, and these include Escherichia/Shigella, and Granulicatella species, and Streptococcus mitis/pneumoniae groups. In both cases and controls, there tend to be distinct negative correlations between facultative anaerobic lineages and obligate anaerobic lineages. Overall genus-level microbiota composition exhibit a shift in controls from low to high levels of Prevotella and in MSD cases from high to low levels of Escherichia/Shigella in younger versus older children; however, there was significant variation among many genera by both site and age. Conclusions Our findings expand the current understanding of microbiota-associated diarrhea pathogenicity in young children from developing countries. Our findings are necessarily based on correlative analyses and must be further validated through epidemiological and molecular techniques.