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Intestinal microbiome changes in response to amino acid and micronutrient supplementation: secondary analysis of the AMAZE trial.

Microbial dysbiosis has been linked to environmental enteropathy (EE) and alterations in nutrient absorption; however, compositional modifications following exposure to supplementary nutrients are poorly understood. Here, we report the effect of amino acid and micronutrient supplementation on the gut microbiome of adults with EE. In the AMAZE trial, adults with EE were randomized to amino acids (AA) and/or micronutrients (MM) for 16 weeks in a 2 × 2 factorial design against placebo. Endoscopy was performed before and after intervention, during which duodenal aspirates were collected as well as fecal samples. 16S rRNA amplicon sequencing was performed on both these samples, and differences in bacterial community composition before and after interventions were investigated using differential abundance analysis, corrected using false discovery rate, plus alpha and beta diversity measurements. HIV seropositive participants exhibited lower alpha and beta diversity at baseline. AA and/or MM supplementation did not show significant changes in abundance or diversity of genera post-intervention compared to placebo. Micronutrient supplementation resulted in an increase in the pyruvate fermentation to acetone MetaCyc pathways compared to the placebo arm. This study provides insights into the responsiveness of the gut microbiome to micronutrient and amino acid supplementation in adults with EE.

HIV

Gluten-sensitive enteropathy: genetic analysis and organ culture study in 35 families.

The genetic marker histocompatibility antigen HLA-B8 is present in 80% of patients with gluten-sensitive enteropathy (GSE). We studied 35 families with at least one affected member to determine whether an HLA-region gene alone could determine susceptibility to GSE. The incidence of HLA-B8 in the patients was 69% vs 22% for normals (P less than 0.001). The incidence of GSE in HLA-genotype-identical siblings of patients was only 8%, and in HLA-B8-haplotype-identical siblings and parents of patients was only 14% and 5%, respectively. In addition, intestinal biopsies of HLA-identical or partially identical relatives of patients were studied in an in vitro organ culture system capable of detecting gluten sensitivity in subjects ingesting a normal diet. The results confirmed the low incidence of gluten sensitivity in these individuals. The organ culture system could not differentiate mucosa obtained from unaffected parents or siblings of patients with GSE (who presumably carry the HLA-associated genetic information) from mucosa obtained from normals. We conclude that the genetic material inherited with HLA-B8 alone is not sufficient to produce clinical or subclinical disease. Other genetic and environmental factors appear to be important for disease pathogenesis.

Adolescent