Duodenal Microbiota in Stunted Undernourished Children with Enteropathy

Abstract

BACKGROUND Environmental enteric dysfunction (EED) is an enigmatic disorder of the small intestine postulated to play a role in childhood undernutrition, a pressing global health problem. Defining the incidence of EED, its pathophysiology, and its contribution to impaired linear and ponderal growth has been hampered by the difficulty in directly sampling the small intestinal mucosa and microbial community (microbiota). METHODS Slum-dwelling Bangladeshi children aged 18±2 months, with linear growth-faltering (stunting) who failed a nutritional intervention underwent endoscopy to obtain duodenal biopsies and aspirates. Levels of 4077 plasma proteins and 2619 duodenal proteins were quantified in 80 children with histopathologic evidence of EED, and the abundances of bacterial strains in their duodenal microbiota were determined using culture-independent methods. Young germ-free mice, fed a Bangladeshi diet, were colonized with bacterial strains cultured from the duodenal aspirates. RESULTS The absolute abundances of a shared group of 14 bacterial strains recovered from the duodenums of children with EED and not typically classified as enteropathogens were negatively correlated with linear growth (length-for-age Z-score;β=-0.38±0.12(SEM);ρ=-0.49;p=0.003), and positively correlated with duodenal proteins involved in immunoinflammatory responses. Representation of these 14 duodenal taxa was significantly different in fecal microbiota from EED versus healthy children (p<0.001;PERMANOVA). Gnotobiotic mice colonized with cultured EED-donor duodenal strains develop a small intestinal enteropathy. CONCLUSIONS These results provide evidence of a causal relationship between components of the small intestinal microbiota, enteropathy and stunting and offer a rationale for developing therapeutics that target what must no longer remain terra incognita-the small intestinal microbiota. ClinicalTrials.gov identifier: NCT02812615

Food Insecurity, Malnutrition, and the Microbiome

“…Similarly, recently published data in the New England Journal of Medicine reported that enteric dysfunction played a significant role in childhood undernutrition. The authors elucidated and reported a possible causal relationship between growth stunting and enteric bacteria [24]. In this study, 110 children living in a low-income neighborhood in Bangladesh who had not benefited from nutritional intervention underwent upper endoscopy and small bowel biopsy confirming the diagnosis of Environmental Enteric Dysfunction (EED).…”

Goat Milk Improves Glucose Homeostasis via Enhancement of Hepatic and Skeletal Muscle AMP‐Activated Protein Kinase Activation and Modulation of Gut Microbiota in Streptozocin‐Induced Diabetic Rats

“…Accordingly, it remains unknown the microbiota and metabolites and their relationship with the intestinal cells in the small intestine and the distal parts of the large intestine. [ 33 ] Finally, the effects of goat milk consumption on glucose metabolism need to be investigated in human diabetic subjects.…”

Gut Microbial Dysbiosis in the Pathogenesis of Gastrointestinal Dysmotility and Metabolic Disorders

“…For example, a recent study showed how duodenal microbial dysbiosis is linked with enteropathy and intestinal barrier dysfunction in the environmental enteric dysfunction (EED) condition. 125 EED is a subclinical syndrome characterized by intestinal villous blunting, reduced absorptive capacity, and increased intestinal inflammation. 125 , 126 Furthermore, there have been several metabolic consequences, such as malnutrition and stunting, in patients with EED.…”

“… 125 EED is a subclinical syndrome characterized by intestinal villous blunting, reduced absorptive capacity, and increased intestinal inflammation. 125 , 126 Furthermore, there have been several metabolic consequences, such as malnutrition and stunting, in patients with EED. However, findings from this study raise additional questions: is environmental enteropathy caused by a form of bacterial overgrowth in the small intestine?…”