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Diarrheal diseases can be life-threatening, and 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, or microorganisms that may cause disease, to severe diarrheal disease, as well as distortions in normal gut microbiota composition that might facilitate severe disease. The gut microbiota, occasionally referred to as gut flora, is the specific population and species of bacteria that reside in the human intestine. It contains trillions of microrganisms spanning over a 1000 species, each with their own genetic material. Traces of the gut microbiota can also be found in human fecal matter, which allows us to study how unique compositions of bacteria may relate to disease.

In this study, we use a specific method of gene sequencing (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. We found that 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 groups of children, there tend to be distinct negative correlations between facultative anaerobic lineages (i.e. divisions of organisms that can use oxygen but do not require it to produce energy) and obligate anaerobic lineages (i.e. divisions of organisms that are damaged or killed by normal levels of oxygen in the atmosphere). Overall genus-level microbiota composition exhibit a shift in controls from low to high levels of a microorganism called Prevotella in younger versus older children. In MSD cases there is a shift from high to low levels of Escherichia/Shigella in younger versus older children. However, it is important to note that there was significant variation among many genera, or high level types of mircoorganisms, by both study site and child’s age.

Our findings expand the current understanding of microbiota-associated diarrhea pathogenicity in young children from developing countries. Improving our understanding of these relationships is an important step in determining the cause and potential prevention of life-threatening cases. Our findings are necessarily based on correlations between variables, and must be further validated through epidemiological and molecular techniques.


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