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La pantalla huésped-micróbio-droga-nutriente identifica los efectores bacterianos de la terapia con metformina

Rosina Pryor¹, Povilas Norvaisas², Georgios Marinos³

¹MRC London Institute of Medical Sciences, Du Cane Road, London W12 0NN, UK; Institute of Clinical Sciences, Imperial College London, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, UK; Institute of Structural and Molecular Biology, University College London and Birkbeck, London WC1E 6BT, UK.

|September 3, 2019

Resumen

Los microbios intestinales y la dieta influyen significativamente en la metformina

Área de la Ciencia:

Investigación del microbioma
Farmacología
Enfermedad metabólica

Sus antecedentes:

La metformina es un tratamiento primario para la diabetes tipo 2 y muestra potencial como medicamento antienvejecimiento.
El microbioma intestinal y el estado nutricional son reguladores críticos de la fisiología del huésped y la eficacia del medicamento.

Objetivo del estudio:

Investigar cómo los microbios intestinales y la nutrición modulan los efectos terapéuticos de la metformina.
Para aclarar las complejas interacciones entre el huésped, el microbio, el medicamento y el nutriente.

Principales métodos:

Utilizó una plataforma de cribado de cuatro vías de alto rendimiento con Escherichia coli y Caenorhabditis elegans.
Caracterización experimental integrada de los efectos de la metformina después del regulador de Crp.
Modelado metabólico de la microbiota empleado en pacientes diabéticos tipo 2.

Principales resultados:

Se demostró que los microbios integran la metformina y las señales dietéticas a través de la vía de señalización de la fosfotransferasa que converge en Crp.
Se predice la producción microbiana de agmatina como un regulador clave del impacto de la metformina en el metabolismo de los lípidos del huésped y en la esperanza de vida.
Se han identificado interacciones específicas huésped-microbio-fármaco-nutrientes.

Conclusiones:

Las vías de señalización microbiana son fundamentales para la acción de la metformina.
La agmatina surge como un mediador crucial de los efectos de la metformina en el metabolismo del huésped y la longevidad.
La plataforma de detección desarrollada permite el descubrimiento de terapias dirigidas al microbioma para mejorar la salud y la esperanza de vida.

Palabras clave:

C. elegans Señalización por CRP Las Drosophila envejecimiento el régimen alimenticio los humanos Modelado metabólico y metformina el microbioma Diabetes de tipo 2

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