A shared group of bacterial taxa in the duodenal microbiota of undernourished Pakistani children with Environmental Enteric Dysfunction

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. Sixty-three members of a Pakistani cohort identified as being acutely malnourished between 3-6 months of age and whose wasting (weight-for-length z-score; WLZ) failed to improve after a 2-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 referenced to anthropometric indices, histopathologic severity in biopsies, expression of selected genes in the duodenal mucosa, plus fecal levels of an immunoinflammatory biomarker (lipocalin-2). A 'core' group of eight bacterial ASVs were present in the duodenal samples of 69% of participants. Streptococcus anginosus was the most prevalent, followed by Streptococcus sp., Gemella haemolysans, Streptococcus australis, Granulicatella elegans, Granulicatella adiacens and Abiotrophia defective. At the time of EGD, none of the core taxa were significantly correlated with WLZ. Statistically significant correlations were documented between the abundances of Granulicatella elegans and Granulicatella adiacens and expression of duodenal mucosal genes involved in immune responses (DUOXA2, SAA, GZMH). These results suggest that a potential role for members of the oral microbiota in pathogenesis, notably Streptococcus, Gemella and Granulicatella species, warrants further investigation.