ROLE OF THE MICROBIOME FOR THE DEVELOPMENT OF METRITIS IN DAIRY CATTLE AND NOVEL STRATEGIES FOR PREVENTION

Abstract

Metritis is a systemic illness that affects around 20% of dairy cattle, occurring within 21 days post-partum. Among the risk factors associated with the disease are retained placenta, stillbirth, dystocia, ketosis, and hypocalcemia. The main microorganisms associated with the disease are Escherichia coli, Trueperella pyogenes and Fusobacterium necrophorum. Detrimental effects caused by the disease are decreased milk production, increased calving to conception interval, and decreased pregnancy per artificial insemination, with the cost of a single case of metritis being estimated at around $513 ($240 to $884). There is a need for the development of reliable models of metritis induction to better understand the dynamics of microorganism growth and determine the metabolic and clinical alterations associated with the development of the disease. A reliable in vivo model of metritis is also a useful tool to test different strategies to prevent or treat the disease, without using a large number of animals, while also easily determining the physiologic alterations caused by these interventions. This dissertation presents in vivo models of metritis induction in primiparous and multiparous Holstein cows, revealing the microorganisms and metabolic changes associated with the development of the disease. A challenge containing 106 cfu each of E. coli, T. pyogenes and F. necrophorum caused metritis in 80% of multiparous cows, increased rectal temperature and decreased dry matter intake. We also determined that F. necrophorum was the main microorganism associated with the development of the disease. The same dose did not significantly increase the incidence of metritis in primiparous cows, but those cows had a 2.7-times greater hazard of being diagnosed with metritis, associated with reduction in milk production when compared to control cows. Lasty, we present a novel strategy (recombinant bovine interleukin-8, rbIL-8) for the prevention of uterine diseases and for increased milk production as an alternative to the use of antimicrobials to treat the disease. The last chapter discusses the second administration of rbIL-8 in cows that had received the treatment two lactations before, showing that it modulates the uterine microbiome, reducing the bacterial load and controlling the growth of the pathogenic bacterial species Fusobacterium. This dissertation reveals that metritis can be induced in a dose-dependent manner in healthy multiparous cows via infusion of a cocktail containing pathogenic microorganisms described to be associated with the disease, and the main pathogen associated with the disease was Fusobacterium. We also demonstrated the effects of a novel strategy for prevention of metritis, administration of rbIL-8, showing that it controls the growth of Fusobacterium, the microorganism that was found to be relevant for induction of metritis. Further research needs to be conducted to elucidate the reasons that the same model did not induce metritis in primiparous cows.