Associations between Gut, Mammary and Vaginal Microbiomes in Dairy Cattle: Role in Health and Disease

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High producing dairy cows are under significant nutritional and physiological stressors during early to mid-lactation, which predispose them to infectious diseases (e.g., mastitis) and metabolic disorders (e.g., subacute ruminal acidosis). These cows are fed high-energy diets, mainly based on grain, to meet their milk production potential. However, these diets can adversely affect the microbial communities of the digestive tract, disturbing the composition and functionality of microbiome, and the profile of microbially-produced metabolites. Many of these metabolites are signaling molecules that can impact hormonal responses of brain and immunological capacities of the cow. Such alterations not only retroactively affect the microbiomes of the digestive tract, but also influence the microbiomes of other body sites, such as the mammary system and the vaginal tract, resulting in initiation and/or progression of infectious and inflammatory diseases in those systems.******The roles of the mammary microbiome in udder health and the vaginal microbiome in reproductive performance of dairy cows have received limited attention. The ongoing research in my group and others suggests that the mammary and vaginal tract microbiomes undergoes significant changes under metabolic and infectious disease conditions. These altered microbiomes are further disrupted by antibiotics that are prescribed to fight infections, hence reducing the resistant of dairy cows against opportunistic and pathogenic microorganisms.******The main goal of the proposed research is to identify taxa/species within the rumen, mammary, and vaginal tract microbiomes that can serve as early indicators of microbial dysbiosis under various metabolic and infectious conditions. Ultimately, these taxa can be used as biomarkers of health and targeted for development of mini-microbial communities that can be sued for prevention and treatment of associated diseases. To determine these indicator taxa, dairy heifers in early lactation will be fed high-grain diets and subjected to an infectious mastitis challenge, periods of antibiotic therapy and recovery to longitudinally determine the microbiome dynamics. The association between these indicator taxa and susceptibility of dairy heifers to mastitis pathogens will be examined as well. Network modeling will be performed to investigate how vaginal tract microbiome is impacted by the shifts in the digestive tract and mammary microbiome through the cow's altered hormonal and immunological responses. The change in microbiome composition and behavior will be evaluated using 16S rRNA sequencing, metatranscriptomics approaches. The models will be validated using samples from healthy controls and mastitic cows. The use of our in-house high-throughput sequencing platform and bioinformatics pipelines will allow for the comprehensive coverage and characterization of indicator species.**