Ahead of Print -Microbiota that Affect Risk for Shigellosis in Children in Low-Income Countries - Volume 21, Number 2—February 2015 - Emerging Infectious Disease journal - CDC
Volume 21, Number 2—February 2015
Microbiota that Affect Risk for Shigellosis in Children in Low-Income Countries
Diarrheal illness contributes substantially to illness and death in children in low-income countries (1,2). Recent investigations of enteric illness have shown many cases with >1 pathogen identified (3–5). The paradigm of 1 pathogen and 1 disease has been questioned with the advent of microbiological and molecular detection methods that have lower limits of detection. Children in developing countries are exposed to an array of pathogenic organisms. Recent studies have shown a complex relationship between gut microbiota and diarrheal illness; children with severe illness tend to have a less diverse microbiota and a predominance of specific genera of organisms (6). Molecular-based approaches to pathogen detection enhance the ability to quantify the abundance of pathogens shed in the stool.
Two recent studies of children in low-income countries have highlighted the need for pathogen quantitation. Lindsay et al., using the Global Enteric Multicenter Study (GEMS) specimen collection, found that 80% of controls and 89% of case-patients had detectable levels of Shigella spp. (7). To identify which children had shigellosis, Lindsay et al. determined a quantitative threshold and, when applied, it identified twice as many cases compared with standard culture. Platts-Mills et al., in a study of populations with a high prevalence of malnutrition and enteric infections in Tanzania, compared samples taken before and during diarrheal episodes (8). They did not find an association between the presence of any pathogen and diarrhea for 15 pathogens studied (rotavirus, adenovirus, astrovirus, norovirus, sapovirus, Cryptosporidium spp., Giardia lamblia, Campylobacter jejuni, Clostridium difficile,Salmonella spp., Shiga-toxigenic Escherichia coli, Shigella spp./enteroinvasive E. coli [EIEC], enterotoxigenic E. coli [ETEC], typical enteropathogenic E. coli[tEPEC], and enteroaggregative E. coli [EAEC]). However, when they considered quantity of pathogen on a continuous scale, 3 organisms (rotavirus, astrovirus, and Shigella spp.) were associated with diarrhea.
In disease-endemic settings, detection of multiple enteropathogens in asymptomatic and symptomatic children is common (4,9). Samples from one third of patients with diarrhea in a hospital study in Kolkata, India, contained >1 pathogen. Negative associations were demonstrated between Shigella spp. and rotavirus and Shigella spp. and Vibrio cholerae (3). However, a limitation of this study was that it was conducted only in patients with diarrhea. Thus, differential comparisons could not be made between pathogen associations in diarrheal and nondiarrheal samples. A recent study by Taniuchi et al. reported the etiology of diarrheal episodes by using molecular methods in Bangladeshi children during their first year of life. They found that multiple enteropathogens were present by the first month of life in stool specimens from healthy children and from children with diarrhea (4). If multiple pathogens are present, they might interact to increase or decrease the probability of symptomatic infection. Bhavnani et al. reported synergistic effects in rotavirus–G. lamblia and rotavirus–E. coli infections, in which the presence of these co-occurring organisms increased the probability of disease (10).
The gut microbiota are composed of thousands of species that might play a role in the risk for diarrhea. Some Lactobacillus and Veillonella species are potentially protective against diarrhea or serve as markers of healthy gut microbiota (11–13) Probiotic activity has been associated with someLactobacillus spp., bifidobacteria, Veillonella spp., Streptococcus spp., Enterococcus spp., nonpathogenic E. coli, and Saccharomyces boulardii (13). Randomized clinical trials have investigated the role of some Lactobacillus spp. in treating infectious diarrhea and identified that these organisms can provide a benefit in the treatment of acute, infectious, watery diarrhea in infants and young children (12). In this study, we examined relationships between Shigella spp./EIEC, microbiota, and diarrhea by using 16S rRNA marker gene surveys of stool specimens from a large international study of diarrhea in children <5 years of age (9).
At the time of this study, Dr. Lindsay was a research analyst and doctoral student at the University of Maryland, Baltimore, Maryland. Her research interests are identification and quantitation of Shigella spp. and how this pathogen interacts with human gut microbiota.
B.L., J.P.N., and O.C.S. developed the hypotheses; M.M.L., K.K., and J.P.N. led the Global Enteric Multicenter Study; B.L., J.O., M.A.H., M.A., B.T., R.O., A.S.G.F., S.K.D., U.N.I., M.A., D. Sanogo, D. Saha, S.S., T.H.F., D.N., and S.P. collected data and developed and maintain databases; A.W.W., J.N.P., J.P., M.P., and O.C.S. developed and performed 16S rRNA gene sequencing, assembly, and taxonomic identification; S.L., B.L., and S.P. performed laboratory protocols; and B.L., L.S.M., L.H., and H.S. performed analyses.
We thank Carol Tackett for her consultation on clinical terminology and readability.
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Suggested citation for this article: Lindsay B, Oundo J, Hossain MO, Antonio M, Tamboura B, Walker AW, et al. Microbiota that affect risk for shigellosis in children in low-income countries. Emerg Infect Dis. 2015 Feb [date cited]. http://dx.doi.org/10.3201/eid2102.140795
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