{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T17:49:26Z","timestamp":1778780966779,"version":"3.51.4"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T00:00:00Z","timestamp":1754352000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>Subclinical mastitis (SCM) is a widespread but frequently undetected condition in dairy cows, leading to reduced milk quality and compromised animal health. This study utilizes an integrated multi-omics strategy encompassing metabolomics and microbiome analyses to investigate the systemic effects of SCM across four biological matrices: blood, milk, feces, and rumen fluid. Our findings reveal significant alterations in hematological and biochemical parameters, with key biomarkers such as digalacturonic acid and N-\u03b5-methyl-L-lysine indicating systemic metabolic and immune dysregulation. Metabolomic profiling uncovered distinct disease-related metabolic patterns, while 16S rRNA sequencing revealed substantial microbial shifts, particularly involving <jats:italic>Succinivibrio<\/jats:italic> and <jats:italic>Methanobrevibacter<\/jats:italic>, which are implicated in carbohydrate fermentation and methanogenesis. Noteworthy correlations between specific metabolites (e.g., ropinirole, arachidonic acid) and microbial genera (e.g., <jats:italic>Succinivibrionaceae UCG-001<\/jats:italic>, <jats:italic>Alistipes<\/jats:italic>) highlight the complex host-microbiome-metabolite interplay associated with SCM. These findings provide new insights into the pathophysiology of SCM and identify candidate biomarkers for early detection. The integrative multi-omics approach adopted in this study offers a valuable framework for developing innovative diagnostic and therapeutic strategies to enhance dairy cow health and productivity.<\/jats:p>","DOI":"10.3389\/fmicb.2025.1613949","type":"journal-article","created":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T05:25:04Z","timestamp":1754371504000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Cross-matrix multi-omics profiling identifies host\u2013microbe interactions and diagnostic signatures in bovine subclinical mastitis"],"prefix":"10.3389","volume":"16","author":[{"given":"Yuqiong","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiulan","family":"Xie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Youli","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Song","family":"Hua","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"ZhuMing","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhengwei","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haihui","family":"Gao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chenglian","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meizhou","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,8,5]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1175","DOI":"10.3390\/microorganisms9061175","article-title":"Subclinical mastitis in selected bovine dairy herds in North Upper Egypt: assessment of prevalence, causative bacterial pathogens, antimicrobial resistance and virulence-associated genes","volume":"9","author":"Abed","year":"2021","journal-title":"Microorganisms"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"fiad136","DOI":"10.1093\/femsec\/fiad136","article-title":"Metataxonomic analysis of milk microbiota in the bovine subclinical mastitis","volume":"99","author":"Alessandri","year":"","journal-title":"FEMS Microbiol. 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Technol."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"1","DOI":"10.5897\/JVMAH2015.0422","article-title":"Isolation, identification and drug resistance patterns of methicillin resistant Staphylococcus aureus from mastitic cows milk from selected dairy farms in and around Kombolcha, Ethiopia","volume":"8","author":"Tassew","year":"2016","journal-title":"J. Vet. Med. Anim. Health"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"2762","DOI":"10.1039\/c6mb00289g","article-title":"Mastitomics, the integrated omics of bovine milk in an experimental model of Streptococcus uberis mastitis: 3. Untargeted metabolomics","volume":"12","author":"Thomas","year":"2016","journal-title":"Mol. 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Dairy Sci."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"741","DOI":"10.3390\/ani13040741","article-title":"Metabolomic analysis of multiple biological specimens (feces, serum, and urine) by 1H-NMR spectroscopy from dairy cows with clinical mastitis","volume":"13","author":"Zhu","year":"2023","journal-title":"Animals"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"1374911","DOI":"10.3389\/fmicb.2024.1374911","article-title":"Microbiome and metabolome analyses of milk and feces from dairy cows with healthy, subclinical, and clinical mastitis","volume":"15","author":"Zhu","year":"2024","journal-title":"Front. 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