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Bioacumulación de fármacos terapéuticos por las bacterias intestinales humanas
Martina Klünemann1,2, Sergej Andrejev1,3, Sonja Blasche1,4
1European Molecular Biology Laboratory, Heidelberg, Germany.
Nature
|September 9, 2021
Resumen
Las bacterias intestinales pueden almacenar medicamentos, un proceso llamado bioacumulación, que afecta la eficacia y el metabolismo de los medicamentos. Esta interacción afecta la disponibilidad del fármaco, la composición de la microbiota y las respuestas individuales al fármaco.
Área de la Ciencia:
- Microbiología
- Farmacología
- Metabolismo de las drogas
Sus antecedentes:
- Las bacterias intestinales influyen en la disponibilidad y eficacia de los medicamentos.
- La biotransformación es el principal mecanismo propuesto de interacción entre fármacos y microbios.
- El mapeo sistemático de las interacciones entre fármacos y bacterias es un desarrollo reciente.
Objetivo del estudio:
- Para investigar el agotamiento de la droga por las bacterias intestinales.
- Para identificar nuevas interacciones entre bacterias y medicamentos.
- Para aclarar el mecanismo de la bioacumulación de fármacos.
Principales métodos:
- Se analizan 15 fármacos diferentes contra 25 cepas de bacterias.
- Investigación de la bioacumulación de duloxetina mediante la química de clics, el perfil térmico del proteoma y la metabolomía.
- Efectos de prueba en una comunidad microbiana definida y en un modelo animal de Caenorhabditis elegans.
Principales resultados:
- Se identificaron 70 interacciones entre bacterias y fármacos, 29 nuevas.
- Más de la mitad de las nuevas interacciones se atribuyen a la bioacumulación (almacenamiento intracelular de fármacos).
- La bioacumulación de duloxetina altera el metabolismo bacteriano, la composición de la comunidad y la respuesta del huésped.
Conclusiones:
- La bioacumulación es un mecanismo común que altera la disponibilidad de fármacos y el metabolismo bacteriano.
- Esto afecta la composición de la microbiota, la farmacocinética y las respuestas individuales a los fármacos.
- Los hallazgos tienen implicaciones para la medicina personalizada y el desarrollo de medicamentos.
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