Small Intestine Bacterial Overgrowth is associated with increased Campylobacter and epithelial injury in duodenal biopsies of Bangladeshi children.

Small intestine bacterial overgrowth (SIBO) has been associated with enteric inflammation, linear growth stunting, and neurodevelopmental delays in children from low-income countries. Little is known about the histologic changes or epithelial adherent microbiota associated with SIBO. We sought to describe these relationships in a cohort of impoverished Bangladeshi children. Undernourished 12-18-month-old children underwent both glucose hydrogen breath testing for SIBO and duodenoscopy with biopsy. Biopsy samples were subject to both histological scoring and 16s rRNA sequencing. 118 children were enrolled with 16s sequencing data available on 53. Of 11 histological features, we found that SIBO was associated with one, enterocyte injury in the second part of the duodenum (R = 0.21, p = 0.02). SIBO was also associated with a significant increase in Campylobacter by 16s rRNA analysis (Log 2-fold change of 4.43; adjusted p = 1.9 x 10-6). These findings support the growing body of literature showing an association between SIBO and enteric inflammation and enterocyte injury and further delineate the subgroup of children with environmental enteric dysfunction who have SIBO. Further, they show a novel association between SIBO and Campylobacter. Mechanistic work is needed to understand the relationship between SIBO, enterocyte injury, and Campylobacter.

Impact of negative tuberculin skin test on growth among disadvantaged Bangladeshi children.

Millions of children are suffering from tuberculosis (TB) worldwide and often end-up with fatal outcome especially in resource-poor settings. Tuberculin skin test (TST) is a conventionally used diagnostic test, less sensitive but highly specific for the diagnosis of clinical TB especially in undernourished children. However, we do not have any data on the role of TST positivity among the children who received nutritional intervention. Our aim was to examine the growth differences between TST-positive and TST-negative undernourished children aged 12 to 18 months who received nutritional intervention prospectively for 90 feeding days. Our further aim was to explore the determinants of TST positivity at enrollment. TB screening as one of the secondary causes of malnutrition was performed on 243 stunted [length for age Z score (LAZ) <-2 standard deviations] or at-risk of stunting (LAZ score between <-1 and -2 standard deviations) children in a community-based intervention study designed to improve their growth parameters. Differences of growth between TST-positives (n = 29) and TST-negatives (n = 214) were compared using paired samples t-test and multivariable linear regression from anthropometric data collected before and after nutritional intervention. Multivariable logistic regression was used to find out possible predictors of TST positivity using baseline sociodemographic data. Of the 243 children screened, 29 (11.9%) were TST-positive and 11 (4.5%) had clinically diagnosed pulmonary TB. Statistically significant improvement of LAZ and weight for age Z-score (WAZ) were observed among the TST-negative participants at the end of intervention period (p = 0.03 for LAZ and p = 0.01 for WAZ). However, we did not find any association between TST status and response to nutritional intervention in our multivariable linear regression models. Our study findings demonstrated a positive impact of nutritional intervention on growth parameters among TST-negative participants.

Impact of Small Intestine Bacterial Overgrowth on Response to a Nutritional Intervention in Bangladeshi Children from an Urban Community.

Small intestine bacterial overgrowth (SIBO) is prevalent among children living in low-income settings, leading to impaired growth and development. The aim of this study was to assess linear and ponderal growth parameters between malnourished SIBO-positive and SIBO-negative children aged 12-18 months who prospectively underwent a nutritional intervention. A glucose hydrogen breath test to detect SIBO was performed in 194 stunted (length-for-age Z score [LAZ] < -2 standard deviations) or at-risk of stunting (LAZ score between < -1 and -2 standard deviations) children. Participants received nutritional supplementation (egg and milk) in addition to their regular family meals 6 days per week for 90 days. Small intestine bacterial overgrowth was defined as a ≥ 12-ppm rise in breath hydrogen over the patient's baseline during the 3-hour test. Small intestine bacterial overgrowth status before intervention was forced into a multivariable linear regression model to examine its effects on anthropometric changes in response to the intervention. Sociodemographic data at enrollment was analyzed through multivariable logistic regression in an attempt to predict SIBO positivity. Overall, 14.9% (29/194) children were diagnosed with SIBO before the nutritional intervention. No statistically significant difference was observed among SIBO-positive and SIBO-negative groups in terms of their response to the nutritional intervention (SIBO-positive coefficient [95% confidence interval (CI)], P-value for ∆length-for-age Z score -0.003 [-0.14, 0.13], 0.96; ∆weight-for-age Z score -0.05 [-0.20, 0.09], 0.46; and ∆weight-for-length Z score -0.10 [-0.31, 0.10], 0.33). This study demonstrated that a noteworthy proportion of malnourished children living in a disadvantaged urban community were SIBO positive; however, it failed to reveal an association between SIBO status and response to nutritional intervention.

Determinants and Impact of Giardia Infection in the First 2 Years of Life in the MAL-ED Birth Cohort.

BACKGROUND.: Giardia are among the most common enteropathogens detected in children in low-resource settings. We describe here the epidemiology of infection with Giardia in the first 2 years of life in the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development Project (MAL-ED), a multisite birth-cohort study. METHODS.: From 2089 children, 34916 stool samples collected during monthly surveillance and episodes of diarrhea were tested for Giardia using an enzyme immunoassay. We quantified the risk of Giardia detection, identified risk factors, and assessed the associations with micronutrients, markers of gut inflammation and permeability, diarrhea, and growth using multivariable linear regression. RESULTS.: The incidence of at least 1 Giardia detection varied according to site (range, 37.7%-96.4%) and was higher in the second year of life. Exclusive breastfeeding (HR for first Giardia detection in a monthly surveillance stool sample, 0.46 [95% confidence interval (CI), 0.28-0.75]), higher socioeconomic status (HR, 0.74 [95% CI, 0.56-0.97]), and recent metronidazole treatment (risk ratio for any surveillance stool detection, 0.69 [95% CI, 0.56-0.84]) were protective. Persistence of Giardia (consecutive detections) in the first 6 months of life was associated with reduced subsequent diarrheal rates in Naushahro Feroze, Pakistan but not at any other site. Giardia detection was also associated with an increased lactulose/mannitol ratio. Persistence of Giardia before 6 months of age was associated with a -0.29 (95% CI, -0.53 to -0.05) deficit in weight-for-age z score and -0.29 (95% CI, -0.64 to 0.07) deficit in length-for-age z score at 2 years. CONCLUSIONS.: Infection with Giardia occurred across epidemiological contexts, and repeated detections in 40% of the children suggest that persistent infections were common. Early persistent infection with Giardia, independent of diarrhea, might contribute to intestinal permeability and stunted growth.