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.

Sometimes referred to as hidden hunger, micronutrient deficiencies persist on a global scale. For some micronutrients this appears to be due to inadequate intake, for others intake may not match increased requirements. However, for most micronutrient deficiencies there is uncertainty as to the dominant driver, and the question about the contribution of malabsorption is open. Environmental enteropathy (EE), formerly referred to as tropical enteropathy and also referred to as environmental enteric dysfunction, is an asymptomatic disorder of small intestinal structure and function which is very highly prevalent in many disadvantaged populations. Recent studies of the pathology and microbiology of this disorder suggest that it is driven by very high pathogen burdens in children and adults living in insanitary environments and is characterised by major derangements of the epithelial cells of the intestinal mucosa. Transcriptomic data suggest that it may lead to impaired digestion and absorption of macronutrients. Given the very high prevalence of EE, marginal malabsorption could have large impacts at population scales. However, the relative contributions of inadequate soil and crop micronutrient contents, inadequate intake, malabsorption and increased requirements are unknown. Malabsorption may compromise attempts to improve micronutrient status, but with the exception of zinc there is currently little evidence to confirm that malabsorption contributes to micronutrient deficiency. Much further research is required to understand the role of malabsorption in hidden hunger, especially in very disadvantaged populations where these deficiencies are most prevalent.

A child’s diet contains nutrients and other substances that influence intestinal health. The present study aimed to evaluate the relations between complementary feeding, intestinal barrier function and environmental enteropathy (EE) in infants. Data from 233 children were obtained from the Brazilian site of the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development Project cohort study. Habitual dietary intake from complementary feeding was estimated using seven 24-h dietary recalls, from 9 to 15 months of age. Intestinal barrier function was assessed using the lactulose–mannitol test (L–M), and EE was determined as a composite measure using faecal biomarkers concentrations – α-1-antitrypsin, myeloperoxidase (MPO) and neopterin (NEO) at 15 months of age. The nutrient adequacies explored the associations between dietary intake and the intestinal biomarkers. Children showed adequate nutrient intakes (with the exception of fibre), impaired intestinal barrier function and intestinal inflammation. There was a negative correlation between energy adequacy and L–M (ρ = −0·19, P < 0·05) and between folate adequacy and NEO concentrations (ρ = −0·21, P < 0·01). In addition, there was a positive correlation between thiamine adequacy and MPO concentration (ρ = 0·22, P < 0·01) and between Ca adequacy and NEO concentration (ρ = 0·23; P < 0·01). Multiple linear regression models showed that energy intakes were inversely associated with intestinal barrier function (β = −0·19, P = 0·02), and fibre intake was inversely associated with the EE scores (β = −0·20, P = 0·04). Findings suggest that dietary intake from complementary feeding is associated with decreased intestinal barrier function and EE in children.

Environmental enteropathy (EE) is a syndrome of altered small intestine structure and function hypothesized to be common among individuals lacking access to improved water and sanitation. There are plausible biological mechanisms, both inflammatory and non-inflammatory, by which EE may alter the cardiometabolic profile. Here, we test the hypothesis that EE is associated with the cardiometabolic profile among young children living in an environment of intense enteropathogen exposure. In total, 156 children participating in the Peruvian cohort of a multicenter study on childhood infectious diseases, growth and development were contacted at 3–5 years of age. The urinary lactulose:mannitol ratio, and plasma antibody to endotoxin core were determined in order to assess intestinal permeability and bacterial translocation. Blood pressure, anthropometry, fasting plasma glucose, insulin, and cholesterol and apolipoprotein profiles were also assessed. Extant cohort data were also used to relate biomarkers of EE during the first 18 months of life to early child cardiometabolic profile. Lower intestinal surface area, as assessed by percent mannitol excretion, was associated with lower apolipoprotein-AI and lower high-density lipoprotein concentrations. Lower intestinal surface area was also associated with greater blood pressure. Inflammation at 7 months of age was associated with higher blood pressure in later childhood. This study supports the potential for a relationship between EE and the cardiometabolic profile.