A shared group of bacterial taxa in the duodenal microbiota of undernourished Pakistani children with Environmental Enteric Dysfunction
Background Environmental Enteric Dysfunction (EED) is a subclinical syndrome of altered small intestinal function postulated to be an important contributor to childhood undernutrition.  The role of small intestinal bacterial communities in the pathophysiology of EED is poorly defined due to a paucity of studies where there has been direct collection of small intestinal samples from undernourished children.   Methods Sixty-three members of a Pakistani cohort identified as being acutely malnourished between 3-6 months of age and whose wasting (WLZ score) failed to improve after a 3-month nutritional intervention, underwent esophagogastroduodenoscopy (EGD). Paired duodenal luminal aspirates and duodenal mucosal biopsies were obtained from 43 children. Duodenal microbiota composition was characterized by sequencing bacterial 16S rRNA gene amplicons. Levels of bacterial taxa (amplicon sequence variants; ASVs) were correlated with anthropometric indices, histopathologic severity in biopsies, expression of selected genes in the duodenal mucosa, plus EED-associated plasma and fecal proteins.  Results We identified a 'core' group of 8 bacterial amplicon sequence variants (ASVs) that were commonly present in the duodenal samples , with Streptococcus anginosus being the most prevalent, followed by Streptococcus sp., Gemella haemolysans, Streptococcus australis, Granulicatella elegans, Granulicatella adiacens and Abiotrophia defective. The severity of histopathology in biopsies did not significantly correlate with linear growth (length-for-age Z score, LAZ) or levels of blood and fecal biomarkers associated with EED.  The absolute abundances of Streptococcus anginosus in duodenal aspirates was negatively correlated with LAZ, and Granulicatella adiacens positively correlated with ponderal growth (weight-for-height, WLZ) at enrollment; at the time of EGD none of the core taxa were significantly correlated with LAZ or WLZ. Significant correlations were documented between the abundances of Granulicatella adiacens and serum levels of CRP, AGP and IGF1, and between Granulicatella elegans and Streptococcus australis and expression of mediators/biomarkers of immune activation (DUOX2, DUOXA2, CCL5, CD160, NKG7, CD3D, CD160) in duodenal biopsies.  Conclusions These observations reveal a relationship between the absolute abundances of members of a group of 8 shared duodenal bacterial taxa, the majority of which are normal members of the oral microbiota, and biomarkers and mediators of duodenal and systemic inflammation in Pakistani children with histopathologic evidence of EED. The results are consistent with the notion that EED is associated with decompartmentalization of the gut microbiota and suggest that a potential role for members of the oral microbiota in pathogenesis, notably Streptococcus, Gemella and Granulicatella species, warrants further investigation in children and their mothers.