Obesity and insulin resistance are major risk factors for Metabolic Syndrome (MetS) in humans. MetS is associated with many health conditions including cardiovascular disease and type 2 diabetes mellitus. Equine Metabolic Syndrome (EMS) in horses and ponies, is analogous to MetS in humans. EMS, characterised primarily by insulin resistance, is a major risk factor for life-threatening laminitis. Research into the different aspects of EMS in different horse and pony breeds is important to have a better understanding of the condition and to be able to manage and treat affected horses/ponies. The gut microbiota and serum metabolites are important attributes involved in the metabolic status of the human and animal body. Genetics has also been extensively investigated when studying metabolic diseases. In this thesis, the potential association of genetics, gut microbiota and serum metabolites with EMS was investigated in a population of privately owned registered Connemara ponies from around Ireland. In line with this, Chapter 1 presents the current literature starting with the up-to-date definition of the condition and the different methods available to diagnose EMS. It also, presents the effect of the factors influencing EMS including age, sex and pregnancy. Furthermore, it lists the different blood metabolites associated with the diagnosis. The second part of the literature review focuses on the gut microbiota, including the basics of microbiota analysis methods (16sRNA) and the other methods. This section then presents the available data from human and veterinary research literature regarding the association between the gut microbiota and metabolic health. Finally, the last section of the literature review chapter presents the genetics of EMS based on available data from studies on other breeds. Chapter 2 presents an investigation of the prevalence of obesity and associated metabolic derangements in Connemara ponies in Ireland. The study showed that the prevalence of generalised obesity in this Irish native pony breed is almost 30% and that obese ponies are 6.5 times more at risk of having high blood insulin (hyperinsulinaemia). Chapter 3 presents an analysis of the association of EMS with faecal microbiota and serum metabolite differences in two groups: EMS and EMS-free ponies. The results showed altered abundance of certain taxa and classes of metabolites in faecal microbiota and serum-metabolites, respectively, associated with the EMS group. Chapter 4 presents an assessment of the association between genetics and EMS in Connemara ponies using a GWAS study. Although no SNPs reached the significance levels, the top identified SNPs are associated with loci of genes that have been associated with metabolic conditions in other species, including diabetes in humans and obesity in mice. Chapter 5 is a general discussion of the findings from all the chapters in the thesis comparing them with findings presented in the current literature in horses and other species. It also presents a summary of the achieved objectives, limitations and recommendations for future studies. This chapter has drawn and presented conclusions from the three main research chapters.

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