{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T04:55:35Z","timestamp":1776056135471,"version":"3.50.1"},"reference-count":27,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T00:00:00Z","timestamp":1776038400000},"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. Vet. Sci."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Subclinical ketosis (SCK) is a common condition in dairy cows, primarily caused by the excessive accumulation of\n                      <jats:italic>\u03b2<\/jats:italic>\n                      -hydroxybutyrate (BHBA). Research has shown that succinyl-CoA is negatively correlated with the production of hepatic BHBA, while it is positively correlated with the utilization of BHBA in peripheral tissues. This correlation is significantly modulated by thiamine levels. Therefore, the purpose of this study is to investigate whether thiamine serves as a critical rate-limiting cofactor in succinyl-CoA metabolism, potentially enhancing BHBA utilization and reducing the incidence of SCK.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>To verify the purpose of the study, 60 SCK dairy cows with comparable body weight, milk yield, and lactation days were selected from a total of 1,126 dairy cows reared in the same environment. The selection was based on the criterion of blood beta-hydroxybutyrate concentration being greater than 1.2\u202fmmol\/L. Another 12 healthy dairy cows with similar productive performances were enrolled in the control treatment. Milk yield, milk quality, rumen fermentable parameters, rumen and blood metabolomics were measured to investigate the alleviative effects of thiamine on SCK.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results and discussion<\/jats:title>\n                    <jats:p>\n                      The results showed that thiamine significantly decreased plasma BHBA concentrations, milk colony-forming units (CFU), and somatic cell counts, while significantly increasing milk yield, milk fat content, acetate levels, and the acetate-to-propionate (A\/P) ratio compared to SCK cows (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.05). Metabolomic analysis revealed that the upregulated metabolites in both the rumen and blood after thiamine supplementation were significantly enriched in the pathways of pyruvate metabolism, glycolysis or gluconeogenesis, tyrosine metabolism, and glycerophospholipid metabolism, while the downregulated metabolites were mainly enriched in ascorbate and aldarate metabolism, glycerophospholipid metabolism, pentose and glucuronate interconversions, and riboflavin metabolism. Collectively, thiamine supplementation effectively alleviated subclinical ketosis by promoting the mediated catabolism of succinyl-CoA for BHBA utilization, improving ruminal fermentability, and thereby enhancing the milk yield and quality.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fvets.2026.1764526","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T04:36:54Z","timestamp":1776055014000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Metabolomic insights into thiamine-mediated metabolism in treating subclinical ketosis in dairy cows"],"prefix":"10.3389","volume":"13","author":[{"given":"Fuguang","family":"Xue","sequence":"first","affiliation":[{"name":"School of Animal Science and Technology, JiangXi Agricultural University","place":["Nanchang, China"]},{"name":"Institute of Animal Science, Chinese Academy of Agricultural Sciences","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Animal Science, Chinese Academy of Agricultural Sciences","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jintao","family":"Xue","sequence":"additional","affiliation":[{"name":"Testing Center of Gaotang Market Supervision and Administration","place":["Liaocheng, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mengjie","family":"Sun","sequence":"additional","affiliation":[{"name":"School of Animal Science and Technology, JiangXi Agricultural University","place":["Nanchang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benhai","family":"Xiong","sequence":"additional","affiliation":[{"name":"Institute of Animal Science, Chinese Academy of Agricultural Sciences","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,13]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"895468","DOI":"10.3389\/fvets.2022.895468","article-title":"Subclinical ketosis in dairy herds: impact of early diagnosis and treatment","volume":"9","author":"Cascone","year":"2022","journal-title":"Front Vet Sci"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1016\/s0749-0720(15)30103-1","article-title":"Subclinical ketosis in lactating dairy cattle","volume":"16","author":"Duffield","year":"2000","journal-title":"Vet Clin North Am Food Anim Pract"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"838","DOI":"10.1111\/jpn.12141","article-title":"Subclinical ketosis in dairy cows: prevalence and risk factors in grazing production system","volume":"98","author":"Garro","year":"2014","journal-title":"J Anim Physiol Anim Nutr (Berl)"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1016\/j.rvsc.2022.01.003","article-title":"Global prevalence of subclinical ketosis in dairy cows: a systematic review and meta-analysis","volume":"144","author":"Loiklung","year":"2022","journal-title":"Res Vet Sci"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"1676","DOI":"10.1017\/S175173111900034X","article-title":"Invited review: \u03b2-hydroxybutyrate concentration in blood and milk and its associations with cow performance","volume":"13","author":"Benedet","year":"2019","journal-title":"Animal"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"e1525","DOI":"10.1002\/vms3.1525","article-title":"Update on ketosis in dairy cattle with major emphasis on subclinical ketosis and abdominal adiposity","volume":"10","author":"Melendez","year":"2024","journal-title":"Vet Med Sci"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"880","DOI":"10.3168\/jds.2014-8362","article-title":"Risk factors for subclinical and clinical ketosis and association with production parameters in dairy cows in the Netherlands","volume":"98","author":"Vanholder","year":"2015","journal-title":"J Dairy Sci"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1042\/bj3380569","article-title":"Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase: a control enzyme in ketogenesis","volume":"338","author":"Hegardt","year":"1999","journal-title":"Biochem J"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"308","DOI":"10.3349\/ymj.2019.60.3.308","article-title":"A rare cause of life-threatening ketoacidosis: novel compound heterozygous OXCT1 mutations causing Succinyl-CoA:3-Ketoacid CoA transferase deficiency","volume":"60","author":"Kim","year":"2019","journal-title":"Yonsei Med J"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"182.e185","DOI":"10.1016\/j.jcrc.2013.06.008","article-title":"The relationship between lactate and thiamine levels in patients with diabetic ketoacidosis","volume":"29","author":"Moskowitz","year":"2014","journal-title":"J Crit Care"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1097\/PCC.0000000000000302","article-title":"Low thiamine levels in children with type 1 diabetes and diabetic ketoacidosis: a pilot study","volume":"16","author":"Rosner","year":"2015","journal-title":"Pediatr Crit Care Med"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"1818","DOI":"10.3389\/fmicb.2017.01818","article-title":"Illumina sequencing approach to characterize thiamine metabolism related Bacteria and the impacts of thiamine supplementation on ruminal microbiota in dairy cows fed high-grain diets","volume":"8","author":"Pan","year":"2017","journal-title":"Front Microbiol"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1007\/s11306-018-1362-8","article-title":"GC-MS analysis of the ruminal metabolome response to thiamine supplementation during high grain feeding in dairy cows","volume":"14","author":"Xue","year":"2018","journal-title":"Metabolomics"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"875741","DOI":"10.3389\/fvets.2022.875741","article-title":"Microbial and metabolomic insights into the bovine lipometabolic responses of rumen and mammary gland to zymolytic small peptide supplementation","volume":"9","author":"Liu","year":"2022","journal-title":"Front Vet Sci"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"4847","DOI":"10.3168\/jds.2020-19150","article-title":"Hepatic autophagy and mitophagy status in dairy cows with subclinical and clinical ketosis","volume":"104","author":"Shen","year":"2021","journal-title":"J Dairy Sci"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"526","DOI":"10.3390\/biom12040526","article-title":"High lipid content of prey fish and n\u2212 3 PUFA peroxidation impair the thiamine status of feeding-migrating Atlantic salmon (Salmo salar) and is reflected in hepatic biochemical indices","volume":"12","author":"Kein\u00e4nen","year":"2022","journal-title":"Biomolecules"},{"key":"ref17","author":"Makarchikov","year":"2022"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"9892","DOI":"10.3168\/jds.2023-23602","article-title":"Subclinical ketosis leads to lipid metabolism disorder by downregulating the expression of acetyl-coenzyme a acetyltransferase 2 in dairy cows","volume":"106","author":"Zhou","year":"2023","journal-title":"J Dairy Sci"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"15536","DOI":"10.3390\/ijms242115536","article-title":"Changes in plasma pyruvate and TCA cycle metabolites upon increased hepatic fatty acid oxidation and ketogenesis in male wistar rats","volume":"24","author":"Dankel","year":"2023","journal-title":"Int J Mol Sci"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"71","DOI":"10.2323\/jgam.50.71","article-title":"Effects of the overexpression of fructose-1,6-bisphosphate aldolase on fermentation pattern and transcription of the genes encoding lactate dehydrogenase and pyruvate formate-lyase in a ruminal bacterium, Streptococcus bovis","volume":"50","author":"Asanuma","year":"2004","journal-title":"J Gen Appl Microbiol"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"4643","DOI":"10.1007\/s00253-022-12020-y","article-title":"Unique pool of carbohydrate-degrading enzymes in novel bacteria assembled from cow and buffalo rumen metagenomes","volume":"106","author":"Bohra","year":"2022","journal-title":"Appl Microbiol Biotechnol"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"964","DOI":"10.1161\/CIRCULATIONAHA.116.024545","article-title":"High-fiber diet and acetate supplementation change the gut microbiota and prevent the development of hypertension and heart failure in hypertensive mice","volume":"135","author":"Makarchikov","year":"2017","journal-title":"Circulation"},{"key":"ref23","first-page":"50","article-title":"Clinical and etiopathological perspective of vitamin B1 hypersensitivity and an example of a desensitization protocol","volume":"16","author":"Lis","year":"2025","journal-title":"Life (Basel)"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1017\/S0007114518001666","article-title":"Thiamine status, metabolism and application in dairy cows: a review","volume":"120","author":"Pan","year":"2018","journal-title":"Br J Nutr"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1071\/AN14523","article-title":"Effects of different dietary concentrate to forage ratio and thiamine supplementation on the rumen fermentation and ruminal bacterial community in dairy cows","volume":"55","author":"Wang","year":"2015","journal-title":"Anim Prod Sci"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"269","DOI":"10.3389\/fvets.2020.00269","article-title":"Identification of Pathogenic Leptospira Species in the Urogenital Tract of Water Buffaloes (Bubalus bubalis) From the Amazon River Delta Region, Brazil","volume":"7","author":"Guedes","year":"2020","journal-title":"Front Vet Sci"},{"key":"ref27","first-page":"164","article-title":"Nutrient Requirements of Dairy Cattle, 7th rev","year":"2001"}],"container-title":["Frontiers in Veterinary Science"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fvets.2026.1764526\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T04:37:00Z","timestamp":1776055020000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fvets.2026.1764526\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,13]]},"references-count":27,"alternative-id":["10.3389\/fvets.2026.1764526"],"URL":"https:\/\/doi.org\/10.3389\/fvets.2026.1764526","relation":{},"ISSN":["2297-1769"],"issn-type":[{"value":"2297-1769","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,13]]},"article-number":"1764526"}}