Exploring the mechanisms of action of antimicrobial growth promoters in poultry

Antimicrobial growth promoters (AGPs) are antibiotics that have been used since the 1950s to improve the performance of livestock; however, their mechanism of action remains poorly understood. Concerns over antibiotic resistance has led to their use being gradually phased out across the world and alternatives being sought. This thesis aimed to investigate the effects of an AGP (tylosin) on the performance of male and female pedigree broiler chickens and link this to the intestinal microbiota and host responses. The first experimental chapter (Chapter 2 of the thesis) investigated the impact of host genetics on the microbiota by comparing bacterial communities between two pedigree lines in two diverse environments. The results showed an effect of both line and environment on the microbiota of the jejunum and caecum. Chapters 3 to 5 present the results of a large experimental trial that aimed to explore the effects of AGP supplementation on the intestinal microbiota, gut morphology and immune response with the aim to link those with improved performance and feed efficiency. Chapter 3 describes changes in bird performance as a result of AGP supplementation, including an AGP x sex interaction, and the impact of these factors on the caecal microbial communities. The results showed that males experienced higher weight gain as a result of AGP treatment compared to females. The AGP treatment also significantly reduced feed conversion ratio (FCR) in males but this effect was not significant in females. The effect of AGP supplementation on the caecal microbiome was described with large changes noted in alpha and beta diversity, in addition to identification of several specific taxa whose relative abundance was found to differ between treatment groups. Chapter 4 explores AGP-induced changes in the microbiota of the jejunum and describes the differences observed between the luminal and mucosal microbiota, a largely overlooked aspect of the chicken intestinal microbiome. Changes in the jejunum microbiota as a result of AGP treatment varied from that of the caecum. While beta diversity analysis showed shifts in the bacterial communities following AGP supplementation, no change in alpha diversity was found. Several differentially abundant taxa were identified in the jejunum, which were distinct to those of the caecum. The final experimental chapter (Chapter 5) explored other possible mechanisms by which AGP supplementation may promote growth and feed efficiency. Duodenal and jejunal morphology of birds with previously characterised microbiota was compared between groups; AGP supplementation did not change any of the measured variables. There was, however, an effect of sex in the histology with males having longer villi compared to females after adjusting for body weight, which could be associated with improved feed efficiency in male birds. The expression of the pro-inflammatory cytokine interleukin (IL)-18 was also measured in the caecal tonsils from the same birds. These findings add to the understanding of how tylosin improves performance in broilers and show for the first time that the impact of AGP supplementation may be influenced by sex. The results suggest that AGPs may induce a beneficial bacterial environment by suppressing the growth of rare and/or specific taxa. These findings could aid in the discovery and development of new supplements or strategies to improve broiler productivity and health.