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La inflamación intestinal se dirige a la actividad que induce el cáncer de la microbiota
Janelle C Arthur1, Ernesto Perez-Chanona, Marcus Mühlbauer
1Department of Medicine, Pharmacology and Immunology-Microbiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Science (New York, N.Y.)
|August 21, 2012
Resumen
La inflamación promueve el cáncer colorrectal (CRC) al alterar los microbios intestinales. Una bacteria específica, Escherichia coli, que lleva una isla genotóxica, impulsa el crecimiento tumoral en ratones susceptibles, destacando objetivos microbianos para la prevención de la CCR.
Área de la Ciencia:
- Microbiología Microbiología.
- Oncología Oncología Oncología.
- Gastroenterología y Gastroenterología.
Sus antecedentes:
- La inflamación es un factor conocido en el desarrollo del cáncer colorrectal (CRC).
- El papel de la microbiota intestinal en la CCR asociada a la inflamación es cada vez más reconocido.
Objetivo del estudio:
- Investigar cómo los cambios inducidos por la inflamación en la microbiota intestinal afectan la progresión del cáncer colorrectal.
- Para identificar factores microbianos específicos que contribuyen a la tumorigénesis en un modelo de colitis.
Principales métodos:
- Se utilizaron ratones con deficiencia de interleucina-10 (Il10(-/-), susceptibles a la colitis.
- Se administró azoximetano (AOM) para inducir CRC y se realizó la monocolonización con Escherichia coli NC101.1.
- Se empleó secuenciación de alto rendimiento para analizar la composición microbiana intestinal.
- Generó una cepa de E. coli con deficiencia de pks para evaluar el papel de la isla genotóxica de la poliquetida sintasa.
Principales resultados:
- La inflamación alteró la composición microbiana intestinal en ratones Il10(-/-.
- La monocolonización con E. coli NC101 promovió el carcinoma invasivo en ratones Il10(-/-) tratados con AOM.
- La eliminación de la isla genotóxica pks de E. coli redujo la multiplicidad tumoral y la invasión sin afectar la inflamación.
- pks(+) E. coli se encontraron en la enfermedad inflamatoria intestinal humana y en pacientes con CCR.
Conclusiones:
- La colitis promueve la tumorigénesis del CRC al alterar la composición microbiana y expandir las bacterias genotóxicas.
- La isla genotóxica pks de E. coli contribuye a la progresión de la CCR.
- Dirigirse a las bacterias genotóxicas puede ofrecer una estrategia para prevenir o tratar el CCR.
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