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Liver flukes are helminth parasites of ruminants which cause economic losses and adverse effects on animal welfare. The common liver fluke Fasciola hepatica is prevalent in temperate regions, including the UK where up to 80% of dairy herds are exposed to the parasite, whilst the tropical liver fluke, F. gigantica, is found in tropical climates. Both flukes require an intermediate snail host to complete their life cycle, and this determines where infection occurs. Liver fluke is challenging to control, especially in dairy cattle. Chronic liver fluke infection moderates the host immune system towards a non- protective T helper cell type 2 (Th2) / regulatory T cell (Treg) response, characterised by IgG, IL4 and IL10, which suppress T helper cell type 1 (Th1) cytokines such as interferon (IFNγ). Previous studies have shown that this may affect the pathogenesis and diagnosis of other diseases, particularly bovine tuberculosis (bTB). However, most studies have been performed in experimentally infected animals under laboratory conditions, and the importance of the findings have not been verified in naturally infected cattle. The aims of this thesis were to investigate the effects of fluke infection on two mycobacterial diseases, bTB and Johne’s disease, and on the food poisoning bacterium Eschericia coli O157. Chapter 2 describes the dynamics of F. hepatica exposure in UK herds as measured by antibody detection ELISA. Individual results from 5937 cattle from 30 herds and 24 bulk milk tank results are used. The distributions of the antibody percent positivity (PP) values were right-skewed for all herds. The bulk milk result correlated with individual results. A significant effect of season was seen, but age was not significantly associated with antibody levels, both of which are in agreement with other recent studies. Chapter 3 contains the results of cross sectional and case-control studies looking at the association between liver fluke exposure with the bTB skin test. A comparison of IgG isotype ratios between fluke positive cattle testing positive and negative for bTB is also included. No significant effect was seen, but these studies were underpowered due to difficulties in obtaining samples. Overall there was a trend that fluke antibodies were associated with a decrease in the odds ratio (OR) of a positive bTB skin test. Chapter 4 is a systematic review of the literature on co-infection with liver fluke and tuberculosis. We extracted data on the association between fluke infection and the bTB skin test, interferon gamma test, lesion detection and culture/bacterial recovery. Evidence from nine studies included in the review points to liver fluke infection having the effect of decreasing all of the four measures of bTB diagnosis, but most studies showed a small and/or non-significant effect, and there was a high risk of bias across all studies. In Chapter 5, the hypothesis that there is an association between F. hepatica and Mycobacterium paratuberculosis subsp. avium (MAP, which causes Johne’s disease) was tested. The spatial distribution of MAP was examined using MAP antibody results from 885606 cows from 1245 herds, but no spatial pattern was seen. 3766 samples from 17 herds were tested for MAP antibody and F. hepatica antibody. Subsequently six farms were followed longitudinally for 1 year and up to four samples for each animal were obtained. No association between the two pathogens was found using any of these approaches. Chapter 6 describes a study on co-infection between fluke and E. coli O157 in finishing cattle. A significant association between the log PP of the F. hepatica copro-antigen ELISA and E. coli O157 shedding was found when the fixed effects of day of sampling and the age of the youngest animal in the group, and the random effect of farm were adjusted for, although the result should be interpreted cautiously due to the many study limitations, particularly a very low level of fluke infection. The effect of this association was that a change from the 25th quartile of F. hepatica PP to the 75th quartile corresponded with a 6.7% increased OR of E. coli O157 shedding (p = 0.01). Overall, these findings suggest that fluke infection may have an effect on bTB and E. coli O157 in naturally exposed animals, although conclusive evidence was lacking. Subtle effects may be obscured in field studies due to the large amount of natural variation between animals, and many unknown factors may introduce bias. Concentrating research on particular subgroups of animals that may be disproportionately at risk of adverse effects of co-infection, and evaluating immune profiles alongside diagnostic measures, may help to provide more certain evidence.