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

ABSTRACT: 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.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.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.

SUBMITTER: Pop M

PROVIDER: S-EPMC4072981 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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

Pop Mihai M Walker Alan W AW Paulson Joseph J Lindsay Brianna B Antonio Martin M Hossain M Anowar MA Oundo Joseph J Tamboura Boubou B Mai Volker V Astrovskaya Irina I Corrada Bravo Hector H Rance Richard R Stares Mark M Levine Myron M MM Panchalingam Sandra S Kotloff Karen K Ikumapayi Usman N UN Ebruke Chinelo C Adeyemi Mitchell M Ahmed Dilruba D Ahmed Firoz F Alam Meer Taifur MT Amin Ruhul R Siddiqui Sabbir S Ochieng John B JB Ouma Emmanuel E Juma Jane J Mailu Euince E Omore Richard R Morris J Glenn JG Breiman Robert F RF Saha Debasish D Parkhill Julian J Nataro James P JP Stine O Colin OC

Genome biology 20140627 6

<h4>Background</h4>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.<h4>Results</h4>We use high throughput 16S rRNA gene sequencing to compare fecal microbiota composit ...[more]

PMID: 24995464

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Project description:Altered gut microbiota are assumed to be involved in the pathogenesis of irritable bowel syndrome (IBS). However, gut microbiota alterations reported in different studies are divergent and sometimes even contradictory. To better elucidate the relationship between altered gut microbiota and IBS, we characterized fecal microbiota of diarrhea-predominant IBS (IBS-D) patients and further explored the effect of rifaximin on gut microbiota using bacterial 16S rRNA gene-targeted pyrosequencing. In our study, IBS-D patients defined by Rome III criteria and age-and-gender matched healthy controls (HC) were enrolled to investigate the fecal microbiota alterations. These IBS-D patients were then treated with rifaximin for 2 weeks and followed up for 10 weeks. Fecal microbiota alterations, small intestine bacterial overgrowth (SIBO) and gastrointestinal (GI) symptoms of IBS-D patients were analyzed before and after treatment. Our results showed fecal microbiota richness but not diversity was decreased in IBS-D patients as compared to HC and there were alterations of fecal microbiota at different taxonomy levels. The abundant phyla Firmicutes was significantly decreased and Bacteroidetes was increased in IBS-D patients. Moreover, the alterations of predominant fermenting bacteria such as Bacteroidales and Clostridiales might be involved in the pathophysiology of IBS-D. In addition, rifaximin was effective in terms of SIBO eradication and even GI symptoms of IBS-D patients achieved at least 10-week improvement after treatment. Furthermore, rifaximin induced alterations of some special bacteria rather than affected the overall composition of microbiota in IBS-D patients. Meanwhile, a potential decrease in propanoate and butanoate metabolism was found in these IBS-D patients after rifaximin treatment. Taken together, there were alterations of gut microbiota in IBS-D patients as compared to HC. Rifaximin could relieve GI symptoms, modify gut microbiota in IBS-D patients and eradicate SIBO in those patients with SIBO, suggesting an additional therapeutic mechanism of rifaximin in the treatment of IBS-D. Our findings of compositional gut microbiota alterations in IBS-D and the effect of rifaximin on the gut microbiota implied that altered gut microbiota were associated with the pathogenesis of IBS.

Dataset Information

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

Publications

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

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