Gut Microbiota and the Quality of Oral Anticoagulation in Vitamin K Antagonists Users: A Review of Potential Implications

Abstract

The efficacy and safety of vitamin K antagonists (VKAs) as oral anticoagulants (OACs) depend on the quality of anticoagulation control, as reflected by the mean time in therapeutic range (TTR). Several factors may be involved in poor TTR such as comorbidities, high inter-individual variability, interacting drugs, and non-adherence. Recent studies suggest that gut microbiota (GM) plays an important role in the pathogenesis of cardiovascular diseases, but the effect of the GM on anticoagulation control with VKAs is unknown. In the present review article, we propose different mechanisms by which the GM could have an impact on the quality of anticoagulation control in patients taking VKA therapy. We suggest that the potential effects of GM may be mediated first, by an indirect effect of metabolites produced by GM in the availability of VKAs drugs; second, by an effect of vitamin K-producing bacteria; and finally, by the structural modification of the molecules of VKAs. Future research will help confirm these hypotheses and may suggest profiles of bacterial signatures or microbial metabolites, to be used as biomarkers to predict the quality of anticoagulation. This could lead to the design of intervention strategies modulating gut microbiota, for example, by using probiotics.

From Pre- and Probiotics to Post-Biotics: A Narrative Review

“…lactis and spp. cremoris that mainly produce MK-8 and MK-9; and Bacteroides fragilis, which produces MK-10, MK-11, and MK-12 [ 72 ]. Finally, K2-vitamin form, produced also by L. casei , has shown some promising anti-cancerogenic properties [ 73 ].…”

“…Lower risk of stroke [68][69][70][71][72][73][74][75][76][77][78][79][80][81][82][83][84] mice, n = 6 + 6 + 6 + 6, randomized [73] Reduction of anemia mice [75];…”

Non-vitamin K Antagonist Oral Anticoagulants and Drug-Food Interactions: Implications for Clinical Practice and Potential Role of Probiotics and Prebiotics

“…For example, there are situations in which the population of the bacterial flora of the gut is reduced, causing a decrease in the source of vitamin K production, as in the case of the use of antibiotic therapies. Due to the decrease in vitamin synthesis, the anticoagulant effect may increase, as well as its possible adverse clinical effects ( 37 , 38 ).…”

“…Otherwise, part of the metabolic capacity of gut microbiota is suggested to be closely associated with the presence of the cytochromes, especially CYP3A4-type cytochrome P450, which is highly expressed in the mucosa of the small intestine ( 38 ). Besides, the concomitant function of P-gp and CYP3A4 is particularly important in the gut, which could restrict oral drug bioavailability of a wide variety of substrates, without a clear known implication with NOACs to date ( 39 ).…”

New Paradigms in Antithrombotic Strategies: A Leap into the Future of Cardiovascular Medicine

“…Aside from COVID-19, other contributions focused on some of the hot topics in the antithrombotic research area. Camelo-Castillo and colleagues provided a comprehensive outlook on the interplay between the gut microbiota and the quality of anticoagulation control during treatment with vitamin K antagonists (VKA) [ 12 ], which still represent the therapeutic choice for several medical conditions that require anticoagulation. The relationship between gut microbiota and cardiovascular disease has been one of the most exciting areas of research during the last years [ 13 ], although the complex interplays with treatments and response to drugs are still mostly unknown and will certainly represent a topic of prominent interest in the future.…”