title: 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.
  
  
  BACKGROUND
  Current Controlled Trials ISRCTN31173864.
authors.affiliation: Blizard Institute of Cell and Molecular Science, Barts & The London School of Medicine, Queen Mary University of London, London, UK. m.p.kelly@qmul.ac.uk
authors.forename: Paul
authors.initials: P
authors.lastname: Kelly
authors.forename: Tamara
authors.initials: T
authors.lastname: Shawa
authors.forename: Stayner
authors.initials: S
authors.lastname: Mwanamakondo
authors.forename: Rose
authors.initials: R
authors.lastname: Soko
authors.forename: Geoff
authors.initials: G
authors.lastname: Smith
authors.forename: G Robin
authors.initials: GR
authors.lastname: Barclay
authors.forename: Ian R
authors.initials: IR
authors.lastname: Sanderson
mesh_terms: D000328:Adult; D000368:Aged; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D000906:Antibodies / Q000097:blood; D019587:Dietary Supplements; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D019053:HIV Enteropathy / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007422:Intestines / Q000187:drug effects / Q000503:physiopathology*; D008070:Lipopolysaccharides / Q000097:blood / Q000276:immunology; D008297:Male; D018977:Micronutrients / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008875:Middle Aged; D015999:Multivariate Analysis; D010539:Permeability / Q000187:drug effects; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000097:blood; D013270:Stomach / Q000187:drug effects / Q000503:physiopathology*; D053319:Tumor Necrosis Factor Decoy Receptors / Q000097:blood; D014505:Urban Population; D015024:Zambia
chemical_list: D044966:Anti-Retroviral Agents; D000906:Antibodies; D008070:Lipopolysaccharides; D018977:Micronutrients; D047888:Receptors, Tumor Necrosis Factor, Type I; D053319:Tumor Necrosis Factor Decoy Receptors; C069521:recombinant human tumor necrosis factor-binding protein-1