Effects of ZnO on the pig gut microbiome and performance

A critical period in the life of the pig is immediately post weaning as the piglet switches abruptly from a predominantly milk diet to a predominantly plant based diet and hence undergoes rapid complimentary changes in gut structure, function and microbiome. During this period piglets characteristically fail to maintain their feed intake, lose weight and body condition, and are susceptible to diarrhoea, often caused by enterotoxigenic Escherichia coli (ETEC) K88. Therefore improving piglet performance during this period has both economic and welfare benefits. Currently the main control measure used in the absence of growth promoting antibiotics is the inclusion of pharmacological levels of zinc oxide (ZnO) in piglet diets during the first 14 days after weaning. This helps them to maintain feed intake and gut health. When given a choice between feeds supplemented with ZnO and un-supplemented feed piglets will choose the latter (Reynolds et al. 2011), clearly indicating that ZnO operates via its effects on the intestinal health of the piglet rather than by providing an immediately more palatable feed source, however the mechanism of action of ZnO remains elusive.
In earlier work using microarrays and quantitative real time PCR we identified lower transcript abundance for a number of genes associated with innate immune response and inflammation from the jejunum of pigs that had received ZnO in their diets compared to their non-ZnO fed contemporaries (Sargeant et al., 2010a). This work was then confirmed in vitro using intestinal porcine epithelial cells (IPEC J2; Sargeant et al., 2010b), however ZnO is thought to act primarily via antimicrobial effects hence feeding ZnO modifies the changes in the microbial composition of the piglet gut occurring during the critical post weaning period. Whilst it is generally considered that a healthy gut has a high ratio of lactobacilli to coliforms, in pigs receiving ZnO this ratio is reversed. Using next-generation sequencing it is possible to gain a better understanding of the changes to the gut microbiome which occur in pigs at weaning and how these are affected by feeding ZnO-supplemented diets. A recent study of the human gut has found that diet rapidly and reproducibly altered the microbiome and established links with bacterial species that cause disease. It also identified that foodborne microbes in the diet can actively colonise the gut. This and similar studies in human give us confidence that a metagenomic analysis of the pig gut will establish similar dietary links that can be manipulated by changing feed and farming practise to improve pig health and performance (David et al., 2014).
In the UK/EU ZnO can only be fed for 14 days at 2500ppm Zn provided as ZnO in the diet (3.1g/Kg). Sudden withdrawal of ZnO can negate the performance advantages of initial inclusion presumably by exposing a gut microbiome that we hypothesis has yet to mature. The aims of the current project are to define the changes in the gut microbiome that occur when pigs are weaned onto a diet containing pharmacological concentrations of ZnO, and the further changes that occur when ZnO is abruptly removed. Recent work suggests that lower doses of ZnO combined with gradual removal may be more beneficial for pig performance - is this reflected by less disturbance in the pig gut microbiome or a gradual readjustment to a lower zinc environment? This work is particularly pertinent now as we are facing the possibility on a ban on the use of pharmacological levels of zinc oxide and so it is important to understand how it is acting in the gut and how best therefore to feed piglets in its absence.