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Los simbiontes intestinales alivian el MASH a través de una vía secundaria de biosíntesis de ácidos biliares

Qixing Nie¹, Xi Luo², Kai Wang³

¹Department of Physiology and Pathophysiology, School of Basic Medical Sciences, State Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine, Third Hospital, Peking University, Beijing, China; Center for Obesity and Metabolic Disease Research, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing 100191, China; State Key Laboratory of Food Science and Resources, Key Laboratory of Bioactive Polysaccharides of Jiangxi Province, Nanchang University, Nanchang, China.

|April 23, 2024

Resumen

Los investigadores descubrieron un nuevo ácido biliar producido por los microbios intestinales, el ácido cólico 3-succinilado (3-sucCA), que puede ayudar a controlar la esteatohepatitis asociada a la disfunción metabólica (MASH) al promover bacterias intestinales beneficiosas.

Área de la Ciencia:

Microbiología
Gastroenterología
Enfermedades metabólicas

Sus antecedentes:

El papel de la microbiota intestinal en la esteatohepatitis asociada a la disfunción metabólica (MASH) es significativo pero no está claro desde el punto de vista mecánico.
La identificación de metabolitos microbianos específicos involucrados en la patogénesis de MASH es crucial para el desarrollo terapéutico.

Objetivo del estudio:

Identificar los ácidos biliares de origen microbiano implicados en el MASH.
Aclarar los mecanismos por los que estos metabolitos influyen en la salud del hígado y la progresión de la enfermedad.

Principales métodos:

Desarrollo de una estrategia de enriquecimiento basada en la química de clics para identificar metabolitos microbianos.
Cribado de aislamientos bacterianos humanos para la producción de ácido biliar.
Purificación de proteínas por actividad para identificar las enzimas responsables de la biosíntesis de los metabolitos.
Validación in vitro e in vivo de la producción y función de los metabolitos.

Principales resultados:

Identificación del ácido cólico 3-succinilado (3-sucCA), un nuevo ácido biliar microbiano.
Correlación negativa entre los niveles de 3-sucCA y el daño hepático en pacientes con enfermedad hepática grasa asociada a la disfunción metabólica (MAFLD).
Bacteroides uniformis ha sido identificado como un productor clave de 3-sucCA.
Se ha confirmado que una enzima beta-lactamasa en B. uniformis es responsable de la biosíntesis de 3-sucCA.
Se demostró que el 3-sucCA es un metabolito restringido por el lumen que alivia la MASH al mejorar el crecimiento de Akkermansia muciniphila.

Conclusiones:

El 3-sucCA es un nuevo metabolito microbiano intestinal con implicaciones terapéuticas potenciales para la MASH.
El eje microbiota-hígado intestinal ofrece objetivos para el manejo de MASH a través de la modulación de metabolitos microbianos específicos como el 3-sucCA.
Dirigirse a la producción de B. uniformis o 3-sucCA podría ser una estrategia para mejorar los resultados de MASH.

Palabras clave:

3-sucCA y sus derivados BAS-suc y sus derivados El MAFLD Ácidos biliares acilados Ácido biliar Biosíntesis La microbiota intestinal

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