Mammary and milk microbiomes and metabolomes - Understanding early variation and impacts on risk for mammary inflammation and mastitis

乳房和乳汁微生物组和代谢组 - 了解早期变异及其对乳房炎症和乳腺炎风险的影响

• 批准号: 10449210
• 负责人: MICHELLE Kay MCGUIRE
• 金额: $ 42.86万
• 依托单位: UNIVERSITY OF IDAHO
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-05 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10449210
• 关键词: Address; Affect; American; Animal Welfare; Animals; Antibiotics; Bacteria; Behavioral; Biological Markers; Breast; Breast Feeding; Cattle; Characteristics; Clinical; Complex; Culture Media; DNA sequencing; Development; Disease; Economic Burden; Economics; Etiology; Exclusive Breastfeeding; Fingerprint; Functional disorder; Future; Gland; Goals; Growth; Health; Human; Immune; Immune response; Immunity; Industry; Infant; Inflammation; Inflammatory; Lactation; Light; Machine Learning; Mammary gland; Measures; Metabolic; Metabolism; Methods; Microbe; Microbiology; Milk; Modeling; Modernization; Molecular; Mothers; Newborn Infant; Outcome; Pain; Pattern; Phenotype; Postpartum Period; Prevention; Research; Research Personnel; Risk; Risk Factors; Sampling; Structure; Testing; Therapeutic Intervention; Time; Variant; Woman; Work; bacterial community; case control; cost; design; dysbiosis; experience; high risk; inflammatory marker; inflammatory milieu; macromolecule; mammary; mastitis; mathematical model; meetings; metabolome; metabolomics; microbial; microbial community; microbiome; milk microbiome; milk production; multiple omics; nutrition; offspring; pathogenic bacteria; prevent; preventive intervention; protein metabolite; virtual

PROJECT SUMMARY/ABSTRACT Exclusive breastfeeding for at least 4 mo is considered the optimal form of nutrition for most newborns, yet many women experience substantial roadblocks in meeting this goal. One of the most common reason for lactation cessation is mastitis (inflammation of the breast). Mastitis is also a significant concern for the US dairy industry because, not only does it represent a significant challenge to animal welfare, but it also decreases milk production and is the most common reason animals are treated with antibiotics. Despite decades of research, mastitis prevention and treatment are poorly understood in both species. One reason for this is that, although mastitis has historically been attributed to the presence of bacterial pathogens in the mammary gland, this dogma is now known to be incorrect. Modern advances in the use of DNA sequencing (rather than needing to grow bacteria in culture media) have resulted in a paradigm shift in this regard such that researchers now know that all milk produced by both healthy and mastitic cows and women contains a rich community of microbes. Experts now believe that a dysbiosis in these microbes or a shift in their metabolism causes mammary inflammation. Consequently, we must now re-examine everything we thought we knew about the etiology and risk factors for this disease. Fundamental to filling this research gap is the rigorous characterization of the microbiome in milk produced by healthy and mastitic women and cows; and identification of microbial community “fingerprints” and metabolomic modifiers, thereof, that alter risk of mammary inflammation. In addition, understanding the similarities and dissimilarities in mammary inflammation between cows and women will help researchers understand whether the former can be used as a model for the latter (and vice versa). The overall objectives for this project are to 1) compare and contrast the milk microbiome, its functionality, immune parameters, and inflammatory markers in healthy and mastitic women and cows, and 2) identify milk microbial profiles and their functionality related to risk for mammary inflammation. Our central hypotheses are that 1) mammary inflammation in both species is associated with shifts in microbes and their function, concentrations of selected markers of immunity and mammary inflammation, and that 2) there exist detectable milk microbiome patterns (or functions) that predispose some women and cows to increased risk of inflammation, and these patterns are related to (and perhaps modified by) environmental and behavioral parameters, some of which are currently considered risk factors for mastitis. To test these hypotheses, we will compare healthy and mastitic cows and women (case-control design) during the first 6 wk postpartum (longitudinal, repeated-measures design during a high-risk period in both species). Importantly, we will utilize a multi-omics approach and machine learning to understand complex relationships within and between species. The results of this work will lead to better understanding of how the microbiology of the lactating mammary gland is related to mammary inflammation and will lay the groundwork for future studies to determine how this disease can be prevented and treated.

项目总结/摘要 对于大多数新生儿来说，至少4个月的纯母乳喂养被认为是最佳的营养形式， 许多妇女在实现这一目标方面遇到了巨大的障碍。最常见的原因之一 哺乳停止是乳腺炎（乳房的炎症）。乳腺炎也是美国乳制品的一个重要问题 因为它不仅对动物福利构成了重大挑战，而且还减少了牛奶 这是动物使用抗生素治疗的最常见原因。尽管经过几十年的研究， 乳腺炎的预防和治疗在这两个物种中知之甚少。其中一个原因是，尽管 乳腺炎在历史上被归因于乳腺中存在细菌病原体， 现在知道教条是不正确的。DNA测序的现代进展（而不是需要 在培养基中培养细菌）导致了这方面的范式转变，研究人员现在知道， 所有健康和患乳腺炎的奶牛和妇女所产的牛奶都含有丰富的微生物群落。 专家们现在认为，这些微生物的生态失调或新陈代谢的变化会导致乳腺癌。 炎症因此，我们现在必须重新检查我们认为我们所知道的关于病因和风险的一切。 这种疾病的因素。填补这一研究空白的基础是对 健康和乳腺炎妇女和奶牛生产的牛奶中的微生物组;以及微生物群落的鉴定 本发明还涉及改变乳腺炎症风险的“指纹”及其代谢组学修饰剂。此外，本发明还提供了一种方法， 了解奶牛和女性乳腺炎的相似性和不同性将有助于 研究人员了解前者是否可以用作后者的模型（反之亦然）。整体 该项目的目标是1）比较和对比牛奶微生物组，其功能，免疫 参数和炎症标志物，以及2）鉴定乳微生物 特征及其与乳腺炎症风险相关的功能。我们的主要假设是， 1)这两个物种的乳腺炎与微生物及其功能的变化有关， 选择免疫和乳腺炎症的标志物，以及2）存在可检测的牛奶微生物组 模式（或功能），使一些妇女和奶牛易患炎症的风险增加，这些 模式与环境和行为参数有关（也许被环境和行为参数修改），其中一些是 目前被认为是乳腺炎的危险因素。为了验证这些假设，我们将比较健康和乳腺炎 奶牛和妇女（病例对照设计）在产后前6周（纵向，重复测量 在两个物种的高风险时期设计）。重要的是，我们将利用多组学方法和机器 学习理解物种内部和物种之间的复杂关系。这项工作的结果将导致 更好地了解哺乳期乳腺的微生物学与乳腺癌的关系， 并将为未来的研究奠定基础，以确定如何预防和治疗这种疾病。

项目成果

Comparing Top-Down Proteoform Identification: Deconvolution, PrSM Overlap, and PTM Detection.

比较自上而下的蛋白质相识别：反卷积，PRSM重叠和PTM检测。

• DOI: 10.1021/acs.jproteome.2c00673
• 发表时间: 2023-07-07
• 期刊: JOURNAL OF PROTEOME RESEARCH
• 影响因子: 4.4
• 作者: Tabb, David L.;Jeong, Kyowon;Druart, Karen;Gant, Megan S.;Brown, Kyle A.;Nicora, Carrie;Zhou, Mowei;Couvillion, Sneha;Nakayasu, Ernesto;Williams, Janet E.;Peterson, Haley K.;McGuire, Michelle K.;McGuire, Mark A.;Metz, Thomas O.;Chamot-Rooke, Julia
• 通讯作者: Chamot-Rooke, Julia

Sodium and Potassium Concentrations and Somatic Cell Count of Human Milk Produced in the First Six Weeks Postpartum and Their Suitability as Biomarkers of Clinical and Subclinical Mastitis.

• DOI: 10.3390/nu14224708
• 发表时间: 2022-11-08
• 期刊: NUTRIENTS
• 影响因子: 5.9
• 作者: Pace, Ryan M.;Pace, Christina D. W.;Fehrenkamp, Bethaney D.;Price, William J.;Lewis, Meghan;Williams, Janet E.;McGuire, Mark A.;McGuire, Michelle K.
• 通讯作者: McGuire, Michelle K.