Intestinal antimicrobial gene expression: Impact of micronutrients in malnourished adults during a randomized trial

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 dailyMMsupplement 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 α defensin (HD) 5, HD6, human β-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 ≤18.5), HD5 mRNA was increased by 0.8 log transcripts/μg 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.