Causative Relationship Between Intestinal Microbiota and Environmental Enteric Dysfunction

Microbiota in human intestine
This study assessed the contribution of the proximal small intestinal microbiota to stunting in an undernourished pediatric population who did not respond to nutritional intervention.

A causal relationship between stunted growth and components of the small intestinal microbiota have been established among children with environmental enteric dysfunction (EED). These results, from a diagnostic intervention study, were published in The New England Journal of Medicine.

Children (N=110; aged mean 18.4±2.1 months) with linear growth stunting who lived in an urban slum in Bangladesh were recruited after failing to benefit from nutritional intervention. An endoscopy was performed, and 80 of the participants had biopsy-confirmed EED. Protein levels were quantified using duodenal and plasma samples. Bacterial strains and levels were determined from fecal samples. Healthy, age-matched children in the area donated plasma (n=21) and fecal (n=27) samples for comparison.

Among the study participants, biopsy samples were graded from 0 to 3, in which 0 indicated normal histological features (n=6), 1 indicated histopathological changes (n=41), 2 indicated mild histopathological abnormalities (n=13), and a grade of 3 showed severe abnormalities (n=50).

Five proteins were strongly correlated with the length-for-age z score; 4 were positively correlated (insulin-like growth factor 1 [IGF-1], IGF acid-labile subunit [IGFALS], IGF binding protein 3 [IGFBP-3], and procollagen C endopeptidase enhancer 2 [PCOLCE2] ) and 1 was negatively correlated (IGFBP-2).

From the fecal samples, 165 taxa were identified (at a relative level ≥0.01% in a minimum of 1 sample). Among all taxa, 14 bacterial strains were found in 80% of the children’s samples. These common bacterial taxa were not classified as enteropathogens but were negatively correlated with the length-for-age z score (r, -0.49; P =.003) and positively correlated with proteins associated with immunoinflammatory response (Q <.10). Compared with healthy children, the presence of these 14 common fecal microbiota taxa differed significantly (P <.001).

The major limitation of this study was the amount of missing data. All samples (endoscopic results, biopsies, fecal samples, and blood samples) were not available for all study participants, however, due to the invasive nature of collection and ethical concerns, collecting a more complete dataset was not feasible.

The study authors concluded that these observations confirm a causative link between stunted growth with enteropathy and microbiota in the small intestine. The authors asserted the need for therapies that target the microbial component and may be a possible treatment for EED among children.

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Chen R Y, Kung V L, Das S, et al. Duodenal microbiota in stunted undernourished children with enteropathy [published online July 23, 2020]. N Engl J Med. 2020;383(4):321-333. doi: 10.1056/NEJMoa1916004