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

高产奶牛在泌乳早期至中期处于显著的营养和生理压力下，易患传染病（如乳腺炎）和代谢紊乱（如亚急性瘤胃酸中毒）。这些奶牛被喂食以谷物为主的高能日粮，以满足其产奶潜力。然而，这些饮食会对消化道的微生物群落产生不利影响，扰乱微生物组的组成和功能，以及微生物产生的代谢物的分布。这些代谢物中的许多是信号分子，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影响消化道的微生物组，还会影响其他身体部位的微生物组，如乳腺系统和阴道，导致这些系统中感染性和炎症性疾病的发生和/或进展。******乳腺微生物组在奶牛乳腺健康中的作用以及阴道微生物组在奶牛生殖性能中的作用受到的关注有限。我的小组和其他人正在进行的研究表明，在代谢和感染性疾病条件下，乳腺和阴道微生物组发生了重大变化。这些改变了的微生物组进一步被用于对抗感染的抗生素破坏，从而降低了奶牛对机会性和致病性微生物的抵抗力。******本研究的主要目标是确定瘤胃、乳腺和阴道微生物组中的分类/物种，这些分类/物种可以作为各种代谢和感染条件下微生物生态失调的早期指标。最终，这些分类群可以用作健康的生物标志物和开发可用于预防和治疗相关疾病的微型微生物群落的目标。为了确定这些指标分类群，泌乳早期的奶牛将被喂食高谷物饲料，并接受感染性乳腺炎挑战，抗生素治疗和恢复期间，以纵向确定微生物组动态。这些指标分类群与奶牛对乳腺炎病原体的易感性之间的关系也将被检查。网络建模将被执行，以调查阴道微生物组是如何通过奶牛改变的激素和免疫反应受到消化道和乳腺微生物组变化的影响。微生物组组成和行为的变化将使用16S rRNA测序和亚转录组学方法进行评估。这些模型将使用健康对照和乳牛的样本进行验证。使用我们内部的高通量测序平台和生物信息学管道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.**