Effect of intestinal microbiome on anticoagulant response of vitamin K antagonists (Homo sapiens)

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1 Intestine LiverCoumarins (4-hydroxycoumarins)Most commonly used VKAsVKANPC1L1Lithocholic acid1-butyratePPAR alphaVitamin K absorptionmenaquinonephylloquinoneCYP2C9PXRVDRWarfarinCD3611SR-BImenaquinone1PPAR betaCoumatetralylPhenprocoumonAcenocoumarolApaxibandicoumarolTioclomarolBrodifacoumPindoneChlorophacinoneDiphacinoneAnisindioneFluindionePhenindioneIndandionesLeft: rodenticides, 'first-generation' anticoagulants.Right: anticoagulants more toxic than warfarin, rarely used.VKA metabolites


A hypothetical pathway showing the interactions of metabolites produced by the intestinal microbiome, which can affects the anticoagulant response of vitamin K antagonists (VKAs).

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Ontology Terms



  1. Han Yan, Yi Chen, Hong Zhu, Wei-Hua Huang, Xin-He Cai, Dan Li, Ya-Juan Lv, Si-Zhao, Hong-Hao Zhou, Fan-Yan Luo, Wei Zhang, Xi Li; ''The Relationship Among Intestinal Bacteria, Vitamin K and Response of Vitamin K Antagonist: A Review of Evidence and Potential Mechanism''; Front Med (Lausanne), 2022 PubMed Europe PMC Scholia


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123985view10:51, 9 September 2022EweitzModified title
123592view13:38, 4 August 2022DeSlUpdate HGNC IDs to UniProt
123591view13:36, 4 August 2022DeSlUpdated description
123590view13:35, 4 August 2022DeSlOntology Term : 'hepatocyte' added !
123589view13:35, 4 August 2022DeSlOntology Term : 'gut absorptive cell' added !
123588view13:34, 4 August 2022DeSlOntology Term : 'vitamin and vitamin metabolites signaling pathway' added !
123587view13:34, 4 August 2022DeSlOntology Term : 'vitamin K deficiency bleeding' added !
123586view13:34, 4 August 2022DeSlOntology Term : 'vitamin K antagonist drug pathway' added !
123585view13:33, 4 August 2022DeSlAdded more comments for datanodes
123584view13:25, 4 August 2022DeSlNew pathway

External references


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NameTypeDatabase referenceComment
1-butyrateMetaboliteCHEBI:17968 (ChEBI)
  • short-chain fatty acids (SCFAs); other SCFAs prodcued by the intestinal bacteria are propionic and acetic acids.
  • butyrate could reduce the absorption of dietary cholesterol by downregulating the expression of NPC1L1 in the intestines
  • Butyrate is Peroxisome Proliferator-Activated Receptor (PPAR) agonist (dor both PPARα and PPARβ)
AcenocoumarolMetaboliteCHEBI:53766 (ChEBI)
AnisindioneMetaboliteCHEBI:133809 (ChEBI)
ApaxibanMetaboliteCHEBI:72296 (ChEBI) AKA Eliquis, alternative to warfarin
BrodifacoumMetaboliteQ421203 (Wikidata)
CD36GeneProductP16671 (Uniprot-TrEMBL)
CYP2C9GeneProductP11712 (Uniprot-TrEMBL) AKA cytochrome P450 Family 2 Subfamily C Member 9.
ChlorophacinoneMetaboliteQ413488 (Wikidata)
CoumatetralylMetaboliteQ415772 (Wikidata)
DiphacinoneMetaboliteCHEBI:81896 (ChEBI)
FluindioneMetaboliteQ3074488 (Wikidata)
Lithocholic acidMetaboliteCHEBI:16325 (ChEBI)
  • secondary bile acid produced by intestinal bacteria
  • Could activate PXR (72), and is a vitamin D receptor (VDR) agonist.
NPC1L1GeneProductQ9UHC9 (Uniprot-TrEMBL) AKA NPC1like intracellular cholesterol transporter 1;
PPAR alphaProteinQ07869 (Uniprot-TrEMBL)
  • AKA PPARA, PPARα, the peroxisome proliferator-activated receptor α
  • activation of PPARα and PPARβ will decrease the expression of NPC1L1 in intestines
PPAR betaProteinQ03181 (Uniprot-TrEMBL)
  • AKA PPARB, PPARβ, the peroxisome proliferator-activated receptor β; PPARbeta (formerly PPARdelta)
  • activation of PPARα and PPARβ will decrease the expression of NPC1L1 in intestines
PXRProteinO75469 (Uniprot-TrEMBL)
  • AKA regnane X receptor, NR1I2
  • PXR is a drug-activated nuclear receptor, and has been shown to mediate the transcriptional upregulation of CYP2C gene
PhenindioneMetaboliteCHEBI:8066 (ChEBI)
PhenprocoumonMetaboliteCHEBI:50438 (ChEBI)
PindoneMetaboliteHMDB0256560 (HMDB)
SR-BIProteinQ8WTV0 (Uniprot-TrEMBL) AKA Scavenger receptor class B member 1
TioclomarolMetaboliteCHEBI:135730 (ChEBI)
VDRGeneProductP11473 (Uniprot-TrEMBL)
  • AKA vitamin D receptor
  • VDR is a drug-activated nuclear receptor and has been shown to mediate the transcriptional upregulation of CYP2C gene.
Vitamin K absorptionPathway
WarfarinMetaboliteCHEBI:10033 (ChEBI) AKA Coumadin
dicoumarolMetaboliteCHEBI:4513 (ChEBI)
menaquinoneMetaboliteCHEBI:16374 (ChEBI) Figure in paper describes menaquinone, text mentiones: "MK-4 has been found as the most common menaquinone in humans, as well as the only menaquinone converted by phylloquinone. The other menaquinone is synthesized by some obligate and facultative anaerobic bacteria. Except for MK-4, the other menaquinone in humans is mostly synthesized by intestinal bacteria. [PMID:35510250]. Therefore, annotated with overarching Vit.K2 ID from chebi (which should constitute all subforms)
phylloquinoneMetaboliteCHEBI:28433 (ChEBI)
  • AKA VK1
  • NPC1L1 is a regulatory factor of intestinal phylloquinone absorption

Annotated Interactions

No annotated interactions

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