Gastrointestinal (GI) helminths are amongst the most important infectious agents affecting the welfare and health of livestock animals worldwide. GI helminths are known to interact with the host via several complex mechanisms, that include modulation of the host immune system and of the commensal GI microbiota. For ruminants in particular, the composition of the gut microbiota is key for digestion of foodstuff and processing of nutrients that result in meat, dairy and/or wool production, as well as maintenance of GI membrane health and immune system development and function. Nevertheless, the mechanisms by which GI helminths interact with the ruminant gut microbiota remain largely unknown; moreover, research in this area is hindered by inconsistent methodologies and the use of different parasite-host pairs across studies aimed to elucidate the qualitative and quantitative alterations in gut microbiota composition in experimentally and/or naturally helminth-infected ruminants. However, recent findings have suggested that helminth secretions, i.e., excretory-secretory products (ESPs) and extracellular vesicles (EVs), are a rich source of antimicrobial peptides (AMPs) that may be, at least partially, responsible for the observed microbial compositional changes in the ruminant gut. Therefore, the aims of this thesis were to (i) explore the impact of GI helminth infections of ruminants, using the ‘brown stomach worm’ of small ruminants Teladorsagia circumcincta, on the composition of the host gut microbiota and determine the reproducibility of helminth-microbiota interaction data in vivo, (ii) to assess the ability of T. circumcincta to modulate their microbial surroundings through antimicrobial activity of their ESPs and EVs, and (iii) to identify, characterise and recombinantly express putative antimicrobials found within the ESPs and EVs of a range of GI helminths to assess their bactericidal properties against representative Gram-positive and Gram-negative bacteria.

This thesis characterises the microbial changes within the ovine GI tract during T. circumcincta infection, and highlights the need for standardisation of methodology and technical consistency across in vivo helminth-microbiota studies. Furthermore, this thesis provides insights into the mechanisms that may result in helminth-driven changes in gut microbiota composition. Data from this thesis demonstrate that T. circumcincta ESP exert antimicrobial activity against E. coli, and follow-up bioinformatics analysis of proteomics sequence data identified putative antimicrobials within worm ESPs. Further bioinformatics analyses of available proteomics sequence data of ESPs and EVs of multiple species of GI helminths resulted in the identification of a number of putative antimicrobial peptides, proteins and enzymes. Two putative helminth-derived antimicrobials were recombinantly expressed, and their antimicrobial activity, and mechanism of action, against B. subtilis was assessed experimentally. The data presented in this thesis provides a solid foundation for future research aimed at deepening current understanding of the impact of infections by parasitic helminths on the host gut microbiota, and the intricate mechanisms governing these interactions. Ultimately, knowledge of parasite-microbiota relationships may prove key to the development of novel and efficacious strategies for infection control.