Environmental enteric dysfunction and small intestinal histomorphology of stunted children in Bangladesh

Abstract

There is lack of information on the histological characteristics of the intestinal mucosa in Bangladeshi children. Collection of intestinal biopsy samples and assessment of the histomorphological features is considered to be the traditional gold standard for diagnosis of environmental enteric dysfunction (EED). The purpose of the study was to evaluate the intestinal histological characteristics of stunted children aged between 12–18 months with possible EED. 110 children with chronic malnutrition (52 stunted with length-for-age Z score, LAZ<-2 and 58 at risk of stunting with LAZ <-1 to -2) from the Bangladesh Environmental Enteric Dysfunction (BEED) study protocol who underwent upper gastrointestinal (GI) endoscopy were selected for this study. To explore the association of EED with childhood stunting, upper GI endoscopy was done and the biopsy specimens were studied for histopathology. Villous height and crypt depth were measured and the presence and intensity of inflammatory infiltrates in the lamina propria was investigated. Bivariate analysis was performed to examine the relationship between stunting and histologic morphology. More than 90% children irrespective of nutritional status were diagnosed to have chronic non-specific duodenitis on histopathology. Half of the children from both groups had villous atrophy as well as crypt hyperplasia and lymphocytic infiltration was present in more than 90% children, irrespective of groups. However, no statistically significant difference was observed when compared between the groups. The prevalence of chronic non-specific duodenitis in Bangladeshi children, irrespective of nutritional status, was high. A significant number of these children had abnormal findings in intestinal histomorphology. Trial registration number: ClinicalTrials.gov ID: NCT02812615 Date of first registration: 24/06/2016. https://clinicaltrials.gov/ct2/results?cond=NCT02812615&term=&cntry=&state=&city=&dist.

Colonization during a key developmental window reveals microbiota-dependent shifts in growth and immunity during undernutrition

“…S 4 A and Table S 4 A-D). Recent findings from a murine model of undernutrition and EED induced by malnourished diet and adherent invasive Escherichia coli infection likewise reported increased microbiota-directed T regulatory cells, and increased numbers of these cells have also been reported in human cohorts and other murine models of undernutrition [ 20 , 41 , 46 ]. Consistent with these findings, we found increased numbers of Rorγt + FoxP3 + regulatory T cells in the lamina propria of SD-IG mice relative to HD-IG animals (Fig.…”

“…Interestingly, these changes were not present when comparing HD-PW to SD-PW groups, suggesting that shorter villi were not a general consequence of the presence of specific microbes, but depended on when these microbes were encountered. In addition to these quantitative measures, we also subjected sections to blinded scoring using three subjective parameters commonly observed in human intestinal biopsies from patients with undernutrition and EED [ 17 , 35 , 41 ], including immune cell infiltration, villous architecture and enterocyte injury. Surprisingly, we did not identify significant differences in these parameters, which may depend on additional environmental or pathogen exposures not replicated in our model (Fig.…”

Effect of Gut Microbiota-Directed Complementary Food Supplementation on Fecal and Plasma Biomarkers of Gut Health and Environmental Enteric Dysfunction in Slum-Dwelling Children with Moderate Acute Malnutrition

“…First, due to the nature of the intervention, we could not ensure double-masking. Second, while biopsy studies examining the histological features of the intestinal mucosa are currently being conducted in Bangladesh [43], we did not collect intestinal biopsy samples from the children in our study. Finally, this study was exploratory in nature and the sample size determination did not consider changes in the fecal and plasma biomarkers evaluated in this study.…”

Colonization during a key developmental window reveals microbiota-dependent shifts in growth and immunity during undernutrition

“…Interestingly, these changes were not present when comparing HD-PW and SD-PW groups, suggesting that the reduction in villus length was not a general consequence of the presence of specific microbes, but depended on when these microbes were encountered. In addition to these quantitative measures, we also subjected sections to blinded scoring using three subjective parameters commonly observed in human intestinal biopsies from patients with EED 16,30,31 , including immune cell infiltration, villous architecture and enterocyte injury. Surprisingly, we did not identify significant differences in these parameters, which may depend on additional environmental or pathogen exposures not replicated in our model (Fig.…”