Forming 4-methylcatechol as the dominant bioavailable metabolite of intraruminal rutin inhibits p-cresol production in dairy cows

Yue Guo, Wanda J. Weber, Dan Yao, Luciano Caixeta, Noah P. Zimmerman, Jesse Thompson, Elliot Block, Thomas G. Rehberger, Brian A. Crooker, Chi Chen

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Rutin, a natural flavonol glycoside, elicits its diverse health-promoting effects from the bioactivities of quercetin, its aglycone. While widely distributed in the vegetables and fruits of human diet, rutin is either absent or inadequate in common animal feed ingredients. Rutin has been supplemented to dairy cows for performance enhancement, but its metabolic fate in vivo has not been determined. In this study, plasma, urine, and rumen fluid samples were collected before and after the intraruminal dosing of 100 mg/kg rutin to 4 Holsteins, and then characterized by both targeted and untargeted liquid chromatography-mass spectrometry (LC-MS)-based metabolomic analysis. In plasma and urine, 4-methylcatechol sulfate was identified as the most abundant metabolite of rutin, instead of quercetin and its flavonol metabolites, and its concentration was inversely correlated with the concentration of p-cresol sulfate. In rumen fluid, the formation of 3,4-dihydroxyphenylacetic acid (DHPAA) and 4-methylcatechol after rapid degradation of rutin and quercetin concurred with the decrease of p-cresol and the increase of its precursor, 4-hydroxyphenylacetic acid. Overall, the formation of 4-methylcatechol, a bioactive microbial metabolite, as the dominant bioavailable metabolite of rutin and quercetin, could contribute to their beneficial bioactivities in dairy cows, while the decrease of p-cresol, a microbial metabolite with negative biological and sensory properties, from the competitive inhibition between microbial metabolism of rutin and tyrosine, has the potential to reduce environmental impact of dairy operations and improve the health of dairy cattle.

Original languageEnglish (US)
Article number16
Issue number1
StatePublished - Jan 2022

Bibliographical note

Funding Information:
Funding: This study was partially supported by a gift from Church & Dwight. Research efforts by Chen and Crooker are partially supported by the NIFA projects MIN-18-125 and MIN-16-125, respectively.

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.


  • 4-methylcatechol
  • Dairy cow
  • Microbial metabolism
  • P-cresol
  • Quercetin
  • Rutin

PubMed: MeSH publication types

  • Journal Article


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