Effect of intestinal microbiome on anticoagulant response of vitamin K antagonists (WP5273)

Homo sapiens

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

Authors

Denise Slenter and Eric Weitz

Activity

last edited

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Cited In

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Organisms

Homo sapiens

Communities

Annotations

Cell Type Ontology

gut absorptive cell hepatocyte

Pathway Ontology

vitamin and vitamin metabolites signaling pathway vitamin K antagonist drug pathway

Disease Ontology

vitamin K deficiency bleeding

Participants
Query Drugst.One

Label Type Compact URI Comment
1-butyrate Metabolite chebi:17968 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)
Lithocholic acid Metabolite chebi:16325 secondary bile acid produced by intestinal bacteria
Could activate PXR (72), and is a vitamin D receptor (VDR) agonist.
menaquinone Metabolite chebi:16374 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)
Warfarin Metabolite chebi:10033 AKA Coumadin
phylloquinone Metabolite chebi:28433 AKA VK1
NPC1L1 is a regulatory factor of intestinal phylloquinone absorption
menaquinone Metabolite chebi:16374 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)
Coumatetralyl Metabolite wikidata:Q415772
Phenprocoumon Metabolite chebi:50438
Acenocoumarol Metabolite chebi:53766
Apaxiban Metabolite chebi:72296 AKA Eliquis, alternative to warfarin
dicoumarol Metabolite chebi:4513
Tioclomarol Metabolite chebi:135730
Brodifacoum Metabolite wikidata:Q421203
Pindone Metabolite hmdb:HMDB0256560
Chlorophacinone Metabolite wikidata:Q413488
Diphacinone Metabolite chebi:81896
Anisindione Metabolite chebi:133809
Fluindione Metabolite wikidata:Q3074488
Phenindione Metabolite chebi:8066
VDR GeneProduct uniprot:P11473 AKA vitamin D receptor
VDR is a drug-activated nuclear receptor and has been shown to mediate the transcriptional upregulation of CYP2C gene.
NPC1L1 GeneProduct uniprot:Q9UHC9 AKA NPC1like intracellular cholesterol transporter 1;
CYP2C9 GeneProduct uniprot:P11712 AKA cytochrome P450 Family 2 Subfamily C Member 9.
CD36 GeneProduct uniprot:P16671
PXR Protein uniprot:O75469 AKA regnane X receptor, NR1I2
PXR is a drug-activated nuclear receptor, and has been shown to mediate the transcriptional upregulation of CYP2C gene
PPAR alpha Protein uniprot:Q07869 AKA PPARA, PPARα, the peroxisome proliferator-activated receptor α
activation of PPARα and PPARβ will decrease the expression of NPC1L1 in intestines
SR-BI Protein uniprot:Q8WTV0 AKA Scavenger receptor class B member 1
PPAR beta Protein uniprot:Q03181 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

References

  1. The Relationship Among Intestinal Bacteria, Vitamin K and Response of Vitamin K Antagonist: A Review of Evidence and Potential Mechanism. Yan H, Chen Y, Zhu H, Huang WH, Cai XH, Li D, et al. Front Med (Lausanne). 2022 Apr 18;9:829304. PubMed Europe PMC Scholia