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Predecir y manipular la inactivación de fármacos cardíacos por la bacteria intestinal humana Eggerthella lenta para
Henry J Haiser1, David B Gootenberg, Kelly Chatman
1Faculty of Arts and Sciences Center for Systems Biology, Harvard University, Cambridge, MA 02138, USA.
Science (New York, N.Y.)
|July 23, 2013
Resumen
La bacteria intestinal Eggerthella lenta inactiva el medicamento cardíaco digoxina a través de un operón citocromo específico. La ingesta de proteínas dietéticas influye en este metabolismo microbiano, afectando los niveles de fármacos en el cuerpo.
Área de la Ciencia:
- Microbiología Microbiología.
- Farmacología Farmacología.
- La genómica es la genómica.
Sus antecedentes:
- El microbioma gastrointestinal humano tiene un impacto significativo en la eficacia y toxicidad de los medicamentos.
- Los mecanismos subyacentes a las interacciones entre el microbioma y los medicamentos a menudo se comprenden mal.
Objetivo del estudio:
- Para aclarar el mecanismo por el cual el intestino Actinobacterium Eggerthella lenta inactiva el medicamento cardíaco digoxina.
- Para investigar la influencia de la dieta del huésped en el metabolismo de este fármaco microbiano.
Principales métodos:
- Perfilamiento de la transcripción de E. lenta expuesta a digoxina.
- Genómica comparativa para identificar los elementos genéticos relevantes.
- Pruebas basadas en cultivos para confirmar la actividad metabólica.
- Estudios de farmacocinética en ratones gnotobióticos.
Principales resultados:
- Se identificó un operón citocromo regulado por la digoxina en E. lenta como crucial para la inactivación de la digoxina.
- Este operón fue inhibido por la arginina y ausente en cepas no metabólicas.
- Se demostró que las proteínas dietéticas reducen el metabolismo microbiano in vivo de la digoxina en ratones, alterando las concentraciones de fármaco en suero y orina.
Conclusiones:
- Eggerthella lenta posee un mecanismo específico para la inactivación de la digoxina que involucra un operón citocromo.
- La ingesta de proteínas en la dieta modula el metabolismo in vivo de la digoxina por el microbioma intestinal.
- Los resultados farmacológicos deben considerar la interacción entre los genomas humanos y microbianos.
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