High prevalence of small intestine bacteria overgrowth and asymptomatic carriage of enteric pathogens in stunted children in Antananarivo, Madagascar

Abstract

Environmental Enteric Dysfunction (EED) refers to an incompletely defined syndrome of inflammation, reduced absorptive capacity, and reduced barrier function in the small intestine. It is widespread among children and adults in low- and middle-income countries and is also associated with poor sanitation and certain gut infections possibly resulting in an abnormal gut microbiota, small intestinal bacterial overgrowth (SIBO) and stunting. We investigated bacterial pathogen exposure in stunted and non-stunted children in Antananarivo, Madagascar by collecting fecal samples from 464 children (96 severely stunted, 104 moderately stunted and 264 non-stunted) and the prevalence of SIBO in 109 duodenal aspirates from stunted children (61 from severely stunted and 48 from moderately stunted children). SIBO assessed by both aerobic and anaerobic plating techniques was very high: 85.3% when selecting a threshold of ≥105 CFU/ml of bacteria in the upper intestinal aspirates. Moreover, 58.7% of the children showed more than 106 bacteria/ml in these aspirates. The most prevalent cultivated genera recovered were Streptococcus, Neisseria, Staphylococcus, Rothia, Haemophilus, Pantoea and Branhamella. Feces screening by qPCR showed a high prevalence of bacterial enteropathogens, especially those categorized as being enteroinvasive or causing mucosal disruption, such as Shigella spp., enterotoxigenic Escherichia coli, enteropathogenic E. coli and enteroaggregative E. coli. These pathogens were detected at a similar rate in stunted children and controls, all showing no sign of severe diarrhea the day of inclusion but both living in a highly contaminated environment (slum-dwelling). Interestingly Shigella spp. was the most prevalent enteropathogen found in this study (83.3%) without overrepresentation in stunted children.

Stool biomarkers as measures of enteric pathogen infection in infants from Addis Ababa informal settlements

“…Our work also shows that pathogenic E. coli carriage may be the norm in highly contaminated settings. This is similar to other studies that have reported that a significant proportion of children continue to have sub-clinical pathogen carriage [39][40][41][42]. EPEC, the most detected pathogen, was associated with both acute and chronic inflammation processes.…”

Stunted children display ectopic small intestinal colonization by oral bacteria, which cause lipid malabsorption in experimental models

“…SIBO was assessed by culture as described in ref. 15 DNA Extraction and Sequencing. Samples were extracted by commercial kits (QiaAmp cador Pathogen Mini or cador Pathogen 96 QIAcube HT Kit; Qiagen) following the manufacturer's recommendations with an additional bead-beating step to increase mechanical disruption.…”

“…S8). To this purpose, we tested lipid uptake in murine small intestinal cells (m-IcCl2) exposed to a subset of clinical small intestinal isolates representing the main small intestinal taxa recovered (SI Appendix, Table S5) (15). All oral bacterial strains tested with the exception of Lactobacillus paracasei, a reference strain that showed no change in lipid absorption in previous work (12), significantly decreased 14 C-oleic acid absorption in m-IcCl2 cells compared with control conditions (Fig.…”

Spatiotemporal variation in risk ofShigellainfection in childhood: a global risk mapping and prediction model using individual participant data

“…Bands of elevated prevalence were predicted to the immediate north of the Congo basin and Great Lakes region, just to the north of the Tropic of Capricorn, and in tropical coastal West Africa, consistent with the high rates reported in studies not included in this analysis, such as in the Central African Republic 69 , Guinea Bissau 70 , Mozambique 64 and Madagascar. 71 Zones of high predicted prevalence also occurred in South America, Caribbean Central America, the Ganges–Brahmaputra Delta, and New Guinea among others, and may reflect the secondary influence of static environmental and household-level risk factors. These findings should inform the design and selection of sites for forthcoming phase 3 Shigella vaccine trials 21 , and populations living in these hotspots should be considered high priority for eventual vaccine rollout campaigns.…”