Abstract
BackgroundAlthough micronutrient supplementation can reduce morbidity and mortality due to diarrhoea, nutritional influences on intestinal host defence are poorly understood. We tested the hypothesis that micronutrient supplementation can enhance barrier function of the gut.MethodsWe carried out two sub-studies nested within a randomised, double-blind placebo-controlled trial of daily micronutrient supplementation in an urban community in Lusaka, Zambia. In the first sub-study, gastric pH was measured in 203 participants. In the second sub-study, mucosal permeability, lipopolysaccharide (LPS) and anti-LPS antibodies, and serum soluble tumour necrosis factor receptor p55 (sTNFR55) concentrations were measured in 87 participants. Up to three stool samples were also analysed microbiologically for detection of asymptomatic intestinal infection. Gastric histology was subsequently analysed in a third subset (n = 37) to assist in interpretation of the pH data. Informed consent was obtained from all participants after a three-stage information and consent process.ResultsHypochlorhydria (fasting gastric pH > 4.0) was present in 75 (37%) of participants. In multivariate analysis, HIV infection (OR 4.1; 95%CI 2.2-7.8; P < 0.001) was associated with hypochlorhydria, but taking anti-retroviral treatment (OR 0.16; 0.04-0.67; P = 0.01) and allocation to micronutrient supplementation (OR 0.53; 0.28-0.99; P < 0.05) were protective. Hypochlorhydria was associated with increased risk of salmonellosis. Mild (grade 1) gastric atrophy was found in 5 participants, irrespective of Helicobacter pylori or HIV status. Intestinal permeability, LPS concentrations in serum, anti-LPS IgG, and sTNFR55 concentrations did not differ significantly between micronutrient and placebo groups. Anti-LPS IgM was reduced in the micronutrient recipients (P <0.05).ConclusionsWe found evidence of a specific effect of HIV on gastric pH which was readily reversed by anti-retroviral therapy and not mediated by gastric atrophy. Micronutrients had a modest impact on gastric pH and one marker of bacterial translocation.Trial RegistrationCurrent Controlled Trials ISRCTN31173864
Highlights
Micronutrient supplementation can reduce morbidity and mortality due to diarrhoea, nutritional influences on intestinal host defence are poorly understood
As part of a randomised, placebo-controlled trial of a daily multiple micronutrient supplement [36], we studied several facets of intestinal immunity and here we report our analysis of gastric pH, intestinal permeability, LPS and tumour necrosis factor-α (TNF) concentrations in serum
Gastric pH was reduced at all stages of HIV infection In 203 participants in whom pH was measured in fasting gastric aspirates, the median pH was 3 (IQR 1-5.5)
Summary
Patients were studied during the course of a cluster-randomised, placebo-controlled trial of daily micronutrients supplementation in a community in Lusaka, Zambia. The data were collected at a time when highly active anti-retroviral treatment (HAART) was being introduced into Zambia so some participants had been taking HAART for varying periods of up to 15 months. Two sub-studies were carried out on different groups of participants identified at random during the course of the main trial: (i) measurement of gastric pH (n = 203) in participants who had been taking MM or placebo for between 4 and 19 months (median 9 months, IQR 7-15 months); (ii) studies of intestinal permeability (using four sugars), translocation (using LPS and anti-LPS antibodies) and immune activation (using TNF receptor (TNFR) p55) in 86 participants. Lipopolysaccharide concentrations in serum Lipopolysaccharide (LPS) and anti-lipopolysaccharide antibodies (IgG and IgM) were measured as markers of bacterial translocation. Endotoxin core antibodies (EndoCAb) IgM and IgG were measured by ELISA as previously described [39,40]. To detect a difference between these means, with standard deviation of 44 pg/ml as observed here and with 80% power at 95% confidence, would require 34 in each group
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