Gastric and intestinal barrier impairment in tropical enteropathy and HIV: limited impact of micronutrient supplementation during a randomised controlled trial

Abstract

Background: Although 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.

Methods: We 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.

Results: Hypochlorhydria (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).

Conclusions: We 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 registration: Current Controlled Trials ISRCTN31173864.

Figure 1

Gastric pH in relation to HIV status and anti-retroviral therapy. The difference across all groups was significantly different using the Kruskal-Wallis test (P = 0.0005).

Figure 2

Correlation between serum concentrations of TNFR55 and anti-LPS IgM. The correlation coefficient (r = 0.30, P = 0.006) was derived from log-transformed data.

Figure 3

Gastric histology. Representative histological sections from gastric biopsies from a patient with (A) normal gastric histology and (B) the most severe gastric atrophy observed, which was classified as mild. No moderate or severe atrophy was seen.