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Pharmacological levels of zinc oxide (ZnO) incorporated into the post-weaning piglet diet reduce the incidence of diarrhoea caused by enterotoxigenic Escherichia coli (ETEC) K88. The mechanism for this is not understood. Studies have demonstrated that increasing concentrations of ZnO reduced ETEC K88 adhesion and internalization to the human intestinal cell line Caco-2, and prevented ETEC-induced expression of several inflammatory response genes. This was not due to an antimicrobial effect, and provides a potential mechanism for reduced incidence of post-weaning diarrhoea. However, Caco-2 is a human intestinal cell line, while ETEC K88 is a porcine-specific pathogen. This study, aimed to investigate the effect of ZnO on Intestinal Porcine Epithelial Cells (IPEC) J2, a relevant model for in vitro studies into porcine intestinal host-microbe interactions, specifically ETEC.
ZnO reduced IPEC J2 viability at concentrations ≥200 μM, and ETEC adhesion to the host cell was unaffected by ZnO. Characterisation of the metabolism of IPEC J2 and ETEC established the effects of ZnO treatment on the metabolic profile of both. Although 100 μM ZnO did not inhibit growth of either host or pathogen in fully supplemented media, metabolic profiles were significantly altered. Glucose and mannose were essential energy sources for IPEC J2 in the presence of ZnO, as the ability to utilise other sources was compromised. The increase in specificity of requirements to support respiration in ETEC was more pronounced, in particular the need for cysteine as a nitrogen source. How it has been exposed above, increasing levels of ZnO have previously been shown to reduce adhesion and internalization of ETEC K88 to human Caco-2 in a dose-dependent manner. However, this did not occur in porcine intestinal cells, and no internalization was detected. These disparities are most likely due to different host cell lines. ETEC K88 is a porcine-specific pathogen, and IPEC J2 cells are of the K88ac+ adhesion phenotype. Adherence to porcine and human cells may occur via different mechanisms, perhaps explaining different effects of ZnO on adhesion.
These findings therefore suggest that the role of ZnO in improving piglet health is via a different mechanism to that previously proposed, and that ZnO impacts on both host cell and pathogen metabolism.
HR Sargeant, MA Shaw, M AbuOun, JW Collins, MJ Woodward, RM La Ragione and HM Miller, 2011. Livestock Science, 133: 45?48