title: Intestinal antimicrobial gene expression: impact of micronutrients in malnourished adults during a randomized trial.
abstract: BACKGROUND
  Because both micronutrients and antimicrobial peptides protect against diarrhea, we looked for an effect on intestinal antimicrobial peptide gene expression during a randomized controlled trial of multiple micronutrient (MM) supplementation.
  
  
  METHODS
  Consenting adults (n=287) in Lusaka, Zambia, were randomized to receive a daily MM supplement or placebo and were followed up for 3.3 years, with a crossover after 2 years. Intestinal biopsy samples were obtained at annual intervals, and messenger RNA of the intestinal antimicrobial peptides human alpha defensin (HD) 5, HD6, human beta-defensin (hBD) 1, hBD2, and LL-37 were quantified by real-time reverse-transcriptase polymerase chain reaction. Samples were also obtained during diarrhea episodes and after convalescence.
  
  
  RESULTS
  There was no effect overall of treatment allocation. However, in malnourished adults (body mass index < or =18.5), HD5 mRNA was increased by 0.8 log transcripts/microg total RNA in MM recipients, compared with HD5 mRNA in placebo recipients (P=.007). During diarrhea, HD5 expression was reduced by 0.8 log transcripts in placebo recipients (P=.02) but was not reduced in MM recipients, nor was it reduced after the crossover. Correlations between HD5 and nutritional status were found that were sex-specific but not explained by serum leptin or adiponectin concentrations.
  
  
  CONCLUSIONS
  Micronutrient supplementation was associated with up-regulation of HD5 only in malnourished adults. Interactions between antimicrobial gene expression and nutritional status may help to explain the increased risk of infection in individuals with malnutrition.
authors.affiliation: Institute of Cell and Molecular Science, Barts and The London School of Medicine, Queen Mary University of London, United Kingdom.
authors.forename: Winnie
authors.initials: W
authors.lastname: Dhaliwal
authors.forename: Tamara
authors.initials: T
authors.lastname: Shawa
authors.forename: Moriam
authors.initials: M
authors.lastname: Khanam
authors.forename: Poonam
authors.initials: P
authors.lastname: Jagatiya
authors.forename: Michelo
authors.initials: M
authors.lastname: Simuyandi
authors.forename: Namwiinga
authors.initials: N
authors.lastname: Ndulo
authors.forename: Charles L
authors.initials: CL
authors.lastname: Bevins
authors.forename: Ian R
authors.initials: IR
authors.lastname: Sanderson
authors.forename: Paul
authors.initials: P
authors.lastname: Kelly
mesh_terms: D000328:Adult; D023181:Antimicrobial Cationic Peptides / Q000096:biosynthesis*; D001706:Biopsy; D018592:Cross-Over Studies; D005260:Female; D005500:Follow-Up Studies; D041981:Gastrointestinal Tract / Q000276:immunology*; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D018977:Micronutrients / Q000008:administration & dosage*; D008875:Middle Aged; D010919:Placebos / Q000008:administration & dosage; D012333:RNA, Messenger / Q000032:analysis; D015533:Transcriptional Activation / Q000187:drug effects*; D015024:Zambia
chemical_list: D023181:Antimicrobial Cationic Peptides; D018977:Micronutrients; D010919:Placebos; D012333:RNA, Messenger