Small Intestine Bacterial Overgrowth in Bangladeshi Infants Is Associated With Growth Stunting in a Longitudinal Cohort

Abstract

INTRODUCTION: Small intestine bacterial overgrowth (SIBO) is common in children from low-income countries and has been cross-sectionally associated with growth stunting. We sought to determine whether SIBO was associated with poor growth and neurodevelopmental in a longitudinal analysis. METHODS: We measured SIBO by glucose hydrogen breath test (GHBT) at 18, 52, 78, and 104 weeks of life in a prospective longitudinal birth cohort of Bangladeshi children. Sociodemographic information and measures of enteric inflammation were analyzed as covariates. Diarrheal samples were tested for enteropathogens using polymerase chain reaction. Regression models were created using standardized mean GHBT area under the H 2 curve (AUC) to determine associations with linear growth and cognitive, language, and motor scores on the Bayley-III Scales of Infant and Toddler Development at 2 years. We also investigated associations between GHBT AUC and enteropathogen exposure. RESULTS: A 1-ppm increase in standardized mean GHBT AUC was associated with a 0.01-SD decrease in length-for-age Z score ( P = 0.03) and a 0.11-point decrease in Bayley language score ( P = 0.05) at 2 years of age in adjusted analysis. Enteroaggregative Escherichia coli , Enteropathogenic Escherichia coli, Giardia , and Enterocytozoon bieneusi were associated with increased GHBT AUC, whereas Clostridium difficile , norovirus GI, sapovirus, rotavirus, and Cryptosporidium were associated with decreased GHBT AUC. None were consistent across all 4 time points. DISCUSSION: SIBO in the first 2 years of life is associated with growth stunting and decreased language ability in Bangladeshi infants and may represent a modifiable risk factor in poor growth and neurodevelopment in low-income countries.

Cumulative Febrile, Respiratory, and Diarrheal Illness among Infants in Rural Guatemala and their Association with Neurodevelopmental and Growth Outcomes

“…Accumulating evidence suggests that nutritional deficiency is only one of many contributors to poor neurodevelopmental outcome. 4,8,29,30 Importantly, as was the case with several variables, we did not find an association between cumulative weeks of illness and either stunting or microcephaly, supporting the hypothesis that cumulative febrile/respiratory illnesses may not negatively impact neurodevelopment through stunting or its biological consequences, at least during the short term. Accumulating data from multinational cohorts suggest that neurodevelopment may have a related, but distinct causal pathway from stunting.…”

“…[3][4][5][6][7] Recurrent enteric disease and dysfunction have been tied to both poor neurodevelopment and stunting. 1,8 However, the role and pathogenesis of other types of recurrent infectious diseases, such as febrile and respiratory illnesses, is less well understood. A longitudinal birth cohort study from Bangladesh found that recurrent febrile illness and cytokine profiles associated with both enteric and systemic inflammation were associated with neurodevelopmental delays among infants living in informal urban settlements (slums).…”

Cessation of exclusive breastfeeding and seasonality, but not small intestinal bacterial overgrowth, are associated with environmental enteric dysfunction: A birth cohort study amongst infants in rural Kenya

“…The lack of association between peak breath hydrogen and any EED marker in multivariable models suggests either that its observed variability is not clinically significant or that SIBO, like diarrhoea, is insufficiently common or severe to be a dominant EED risk factor in this setting. Indeed, a recent methodologically similar study of 259 18-week-olds in Bangladesh 11 yielded SIBO (by Rome criteria) prevalence of 11.2% and mean difference between baseline and peak breath hydrogen 4.3 ppm whilst equivalent figures for the 52 participants of this study who underwent GBHT at 17–19 weeks were lower, at 3.8% and 3.0 ppm, respectively.…”

“…9 In low-income settings, abnormal GBHT is associated with stunting, lower socio-economic position, poor sanitation and some markers of EED. 10 , 11 In Brazilian children, abnormal GBHT was associated with higher relative abundance of faecal Salmonella and lower Eubacteria and Firmicutes species. 12 Bacterial overgrowth has been characterised as predominantly oropharyngeal-derived amongst sub-Saharan African children and predominantly Lactobacillus species amongst Bangladeshi toddlers.…”

Giardia and growth impairment in children in high-prevalence settings: consequence or co-incidence?

“…Recent advances in Giardia pathogenesis models are leading the field to examine longstanding questions surrounding the role of persistent Giardia colonization within the broader context of the complex community of intestinal microbiota [45,62–64]. In undernourished children, Giardia co-localizes not only with EED but also with small intestinal bacterial overgrowth (SIBO) [65]. In both experimental models and real-world studies, Giardia associates with a change in the community structure of the intestinal resident microbiota across multiple mammalian hosts [66–68,69 ▪ ].…”