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C9orf72 suprime la inflamación sistémica y neural inducida por las bacterias intestinales

Aaron Burberry^1,2, Michael F Wells^1,2, Francesco Limone^1,2,3

¹Harvard Stem Cell Institute, Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA.

|June 3, 2020

Resumen

La reducción de las bacterias intestinales protege a los ratones con mutaciones en el gen C9ORF72 de enfermedades neurodegenerativas como la esclerosis lateral amiotrófica y la demencia frontotemporal, lo que sugiere intervenciones del microbioma para la salud del cerebro.

Área de la Ciencia:

La neurociencia
La genética
Inmunología

Sus antecedentes:

La expansión repetida de C9ORF72 es una causa común de ELA y FTD.
Esta mutación conduce a la neurodegeneración a través del ARN y la toxicidad de las proteínas.
La reducción de la función C9ORF72 perjudica el control de la inflamación.

Objetivo del estudio:

Identificar los factores genéticos o ambientales que modifican el riesgo de enfermedad por C9ORF72.
Investigar el papel del microbioma intestinal en la neurodegeneración asociada con C9ORF72.

Principales métodos:

Estudió ratones mutantes C9orf72 en entornos con abundancia microbiana alterada.
Se administran antibióticos de amplio espectro para reducir la carga microbiana.
Realizó un trasplante de microbiota intestinal desde un entorno protector.

Principales resultados:

La reducción de las bacterias estimulantes de la inmunidad protegió a los ratones mutantes de la muerte prematura.
La inflamación sistémica y la autoinmunidad mejoraron significativamente.
Los antibióticos y el trasplante de microbiota atenuaron los fenotipos inflamatorios.

Conclusiones:

La composición del microbioma intestinal influye en la neuroinflamación asociada con C9ORF72.
La modulación de la microbiota puede proteger contra la neurodegeneración y la inflamación.
Esto destaca el papel del eje intestino-cerebro en la patogénesis de enfermedades neurodegenerativas.

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