Small Intestine Bacterial Overgrowth and Environmental Enteropathy in Bangladeshi Children

Abstract

Recent studies suggest small intestine bacterial overgrowth (SIBO) is common among developing world children. SIBO's pathogenesis and effect in the developing world are unclear. Our objective was to determine the prevalence of SIBO in Bangladeshi children and its association with malnutrition. Secondary objectives included determination of SIBO's association with sanitation, diarrheal disease, and environmental enteropathy. We performed a cross-sectional analysis of 90 Bangladeshi 2-year-olds monitored since birth from an impoverished neighborhood. SIBO was diagnosed via glucose hydrogen breath testing, with a cutoff of a 12-ppm increase over baseline used for SIBO positivity. Multivariable logistic regression was performed to investigate SIBO predictors. Differences in concomitant inflammation and permeability between SIBO-positive and -negative children were compared with multiple comparison adjustment. A total of 16.7% (15/90) of the children had SIBO. The strongest predictors of SIBO were decreased length-for-age Z score since birth (odds ratio [OR], 0.13; 95% confidence interval [CI], 0.03 to 0.60) and an open sewer outside the home (OR, 4.78; 95% CI, 1.06 to 21.62). Recent or frequent diarrheal disease did not predict SIBO. The markers of intestinal inflammation fecal Reg 1β (116.8 versus 65.6 µg/ml; P = 0.02) and fecal calprotectin (1,834.6 versus 766.7 µg/g; P = 0.004) were elevated in SIBO-positive children. Measures of intestinal permeability and systemic inflammation did not differ between the groups. These findings suggest linear growth faltering and poor sanitation are associated with SIBO independently of recent or frequent diarrheal disease. SIBO is associated with intestinal inflammation but not increased permeability or systemic inflammation.

Importance: A total of 165 million children worldwide are considered stunted, which is associated with increased risk of death prior to age 5 years and cognitive disability. Stunting has, in part, been attributed to the presence of environmental enteropathy. Environmental enteropathy is a poorly understood condition leading to chronic intestinal inflammation. It has been postulated that small intestine bacterial overgrowth contributes to the pathogenesis of environmental enteropathy as overgrowth has been associated with intestinal inflammation and micronutrient malabsorption when it develops in other clinical contexts. This study confirms the finding that overgrowth occurs at high rates in the developing world. This is the first study to show that overgrowth is associated with intestinal inflammation and linear growth delay in this setting and is the first to examine why children with no known gastrointestinal dysfunction develop overgrowth from the developing world environment.

FIG 1

Glucose-hydrogen breath testing results for 90 2-year-olds in Dhaka, Bangladesh, with the change in exhaled breath hydrogen from the patient’s baseline shown on the y axis and time shown on the x axis. (A) Results for small intestine bacterial overgrowth (SIBO)-negative subjects demonstrate no increase in breath hydrogen greater than 12 ppm of exhaled hydrogen over the patient’s own baseline. (B) Results for SIBO-positive subjects demonstrate a peak in exhaled breath hydrogen over the subject’s baseline by >12 ppm.

FIG 2

Inflammatory markers in small intestine bacterial overgrowth (SIBO)-positive and -negative subjects. (A) Calprotectin is a neutrophil-derived protein that, when elevated in the stool, indicates intestinal inflammation. The mean fecal calprotectin level in SIBO-positive subjects was 1,834.6 µg/g compared to 766.7 µg/g in SIBO-negative children (P = 0.004). (B) Reg 1β is a proproliferative, antiapoptotic protein secreted by damaged epithelial cells. When elevated in the stool, it indicates damage to the intestinal epithelium. Children with SIBO had a mean Reg 1β level of 116.8 µg/ml compared to 65.6 µg/ml in SIBO-negative children (P = 0.02).