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

Mihai Pop1, Alan W Walker2, Joseph Paulson1, Brianna Lindsay3, Martin Antonio4, M Anowar Hossain5, Joseph Oundo6, Boubou Tamboura7, Volker Mai8, Irina Astrovskaya1, Hector Corrada Bravo1, Richard Rance2, Mark Stares2, Myron M Levine3, Sandra Panchalingam3, Karen Kotloff3, Usman N Ikumapayi4, Chinelo Ebruke4, Mitchell Adeyemi4, Dilruba Ahmed5, Firoz Ahmed5, Meer Taifur Alam5, Ruhul Amin5, Sabbir Siddiqui5, John B Ochieng6, Emmanuel Ouma6, Jane Juma6, Euince Mailu6, Richard Omore6, J Glenn Morris8, Robert F Breiman9, Debasish Saha4, Julian Parkhill2, James P Nataro10 and O Colin Stine3*

Author Affiliations

1 University of Maryland, College Park, MD, USA

2 Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK

3 University of Maryland, School of Medicine, Baltimore, MD, USA

4 Medical Research Council Unit, Serrekunda, Gambia

5 International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh

6 Kenya Medical Research Institute (KEMRI)-US Centers for Disease Control and Prevention Research Collaboration, Kisumu, Kenya

7 Center for Vaccine Development, Bamako, Mali

8 University of Florida, Gainesville, FL, USA

9 Emory University, Atlanta, Georgia, USA

10 University of Virginia, Charlottesville, VA, USA

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Genome Biology 2014, 15:R76  doi:10.1186/gb-2014-15-6-r76

Published: 27 June 2014

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.