Michelo Simuyandi, Melissa Kapulu, & Paul Kelly
We have previously observed that micronutrient supplementation ameliorated suppression of α-defensin expression during diarrhoea. However, it remains unclear how interactions between antimicrobial peptide (AMP) expression and diarrhoeal disease are altered by micronutrient supplementation. Using oral vaccination as a model of intestinal infection, we measured changes in AMP expression during multiple micronutrient supplementation.
In the first part, volunteers underwent duodenal biopsy before and at 1, 2, 4 or 7 days after administration of one of three live, attenuated oral vaccines against rotavirus, typhoid and enterotoxigenic Escherichia coli. In the second part, participants were randomised to receive a multiple micronutrient supplement or placebo for 6 weeks before undergoing intestinal biopsy, vaccination against typhoid, and re-biopsy after 14 days. Expression of HD5, HD6, hBD1, hBD2, and LL-37 was measured by quantitative RT-PCR.
Taken together, the bacterial vaccines, but not rotavirus vaccine, reduced HD5 expression (P=0.02, signed rank test), and reduced LL-37 expression in 7 of the 8 individuals whose biopsies had expression pre-vaccination (P=0.03). hBD2 was not detected. In the controlled trial, HD5 and HD6 expression after vaccination were lower (median ratio 0.5, IQR 0.07-2.2, and 0.58, IQR 0.13-2.3, respectively) than before vaccination. There was no significant effect detected of micronutrient supplementation on expression of HD5, HD6, hBD1 or LL-37.
We conclude that live attenuated bacterial vaccines, but not rotavirus vaccine, can reduce intestinal α-defensins, and typhoid vaccine reduced LL-37 expression. We found no evidence that micronutrient supplementation in the short term had any impact on antimicrobial peptide expression.
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