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Los efectos químicos globales del microbioma incluyen nuevas conjugaciones de ácido biliar
Robert A Quinn1,2, Alexey V Melnik1, Alison Vrbanac3
1Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, San Diego, CA, USA.
Nature
|February 28, 2020
Resumen
El microbioma altera significativamente la química de los mamíferos en todos los órganos, revelando nuevos conjugados de ácidos biliares. Estos compuestos, que se encuentran en humanos y están relacionados con ciertas enfermedades, afectan las vías de síntesis de ácidos biliares.
Área de la Ciencia:
- Microbiología
- Metabolomía
- La bioquímica
Sus antecedentes:
- El microbioma humano comprende más de 40.000 unidades taxonómicas operativas, que influyen en la salud y las enfermedades del huésped.
- Las moléculas derivadas del microbioma tienen un impacto significativo en la fisiología del huésped, sin embargo, su efecto en la química general del animal está poco explorado.
- La química del ácido biliar se ha estudiado extensamente, pero la influencia microbiana en sus conjugaciones específicas sigue siendo en gran medida desconocida.
Objetivo del estudio:
- Evaluar el impacto del microbioma en la química de los mamíferos utilizando la metabolomía comparativa.
- Identificar nuevas interacciones químicas entre el huésped y el microbioma.
- Investigar el papel de los conjugados de ácidos biliares recién caracterizados en la fisiología y la enfermedad del huésped.
Principales métodos:
- Análisis metabolómico comparativo de ratones libres de gérmenes y de patógenos específicos.
- Informática de espectrometría de masas y visualización de datos para el perfil químico.
- Ensayos in vitro (agonismo de los receptores farnesoides X) y estudios in vivo (análisis de la expresión génica).
Principales resultados:
- La microbiota afecta significativamente la química de todos los órganos de los mamíferos.
- Se identificaron nuevos conjugados de ácido biliar, ácido fenilalanólico, ácido tirosólico y ácido leucocólico.
- Estos conjugados se encontraron en humanos y se enriquecieron en pacientes con enfermedad inflamatoria intestinal y fibrosis quística.
- Los compuestos identificados agonizaron el receptor farnesoide X in vitro y redujeron la expresión génica de síntesis de ácido biliar in vivo.
Conclusiones:
- La microbiota intestinal influye profundamente en el metabolismo del huésped, incluidas las nuevas vías de conjugación de ácidos biliares.
- Los conjugados de ácido biliar recientemente identificados pueden desempeñar un papel fisiológico y están asociados con enfermedades humanas específicas.
- Se necesita más investigación para confirmar la relevancia fisiológica y la contribución a la enfermedad de estos compuestos influenciados por microbios.
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