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

高产奶牛在哺乳早期和中期承受着巨大的营养和生理压力，这使它们容易患上传染病(例如乳房炎)和代谢紊乱(例如亚急性瘤胃酸中毒)。这些奶牛被喂以高能饲料，主要以谷物为基础，以满足它们的产奶潜力。然而，这些饮食可能会对消化道的微生物群落产生不利影响，扰乱微生物群的组成和功能，以及微生物产生的代谢物的特征。这些代谢物中的许多都是信号分子，可以影响大脑的激素反应和奶牛的免疫能力。这种改变不仅会追溯地影响消化道的微生物群，而且还会影响其他身体部位的微生物群，如乳腺系统和阴道，从而导致这些系统中传染病和炎症性疾病的发生和/或发展。我的团队和其他人正在进行的研究表明，在新陈代谢和传染病的条件下，乳腺和阴道的微生物群经历了显著的变化。这些改变的微生物群被抗生素进一步破坏，抗生素用于对抗感染，从而降低奶牛对机会性和病原性微生物的抵抗力。拟议研究的主要目标是确定瘤胃、乳腺和阴道微生物群中可以作为各种代谢和感染条件下微生物失调的早期指示物的分类/物种。最终，这些分类群可用作健康的生物标记物，并可用于开发可用于预防和治疗相关疾病的微型微生物群落。为了确定这些指示分类群，将给哺乳期早期的小母牛饲喂高谷物日粮，并接受感染性乳房炎挑战、抗生素治疗和恢复期，以纵向确定微生物组的动态。还将检查这些指示分类群与奶牛对乳房炎病原体的易感性之间的关系。将进行网络建模，通过改变奶牛的荷尔蒙和免疫反应，研究消化道和乳腺微生物组的变化如何影响阴道微生物组。微生物组组成和行为的变化将使用16S rRNA测序和后转录组学方法进行评估。这些模型将使用来自健康对照和乳房型奶牛的样本进行验证。我们内部的高通量测序平台和生物信息学管道的使用将允许全面覆盖和表征指示物种。**

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.**