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Los metabolitos modulados por la microbiota dan forma al microambiente intestinal mediante la regulación de la
Maayan Levy1, Christoph A Thaiss1, David Zeevi2
1Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
Cell
|December 7, 2015
Resumen
Los metabolitos microbianos como la taurina, la histamina y la espermina regulan la inmunidad intestinal mediante la modulación del inflamatorio NLRP6 y los péptidos antimicrobianos (AMP). Restaurar este equilibrio trata la disbiosis y la colitis.
Área de la Ciencia:
- Microbiología
- Inmunología
- Gastroenterología
Sus antecedentes:
- La coevolución del microbioma huésped es crucial para la homeostasis intestinal y la enfermedad.
- Los principios reguladores del microambiente intestinal, especialmente la participación de los inflamatorios, no se comprenden completamente.
- Se desconocen los metabolitos microbianos específicos que modulan la actividad inflamatoria y la inmunidad intestinal.
Objetivo del estudio:
- Identificar metabolitos microbianos que regulan la interfaz entre el huésped y el microbioma.
- Esclarecer los mecanismos por los que estos metabolitos influyen en la señalización inflamatoria y los perfiles de péptidos antimicrobianos (PMA).
- Investigar el papel de este eje en el mantenimiento de la estabilidad de la comunidad microbiana intestinal y su potencial terapéutico en enfermedades impulsadas por disbiosis.
Principales métodos:
- Se investigó el papel de los metabolitos microbianos (taurina, histamina, espermina) en la modulación de la señalización inflamatoria del NLRP6.
- Se evaluó el impacto de la actividad inflamatoria en la secreción epitelial de IL-18 y los perfiles de péptido antimicrobiano (AMP) posteriores.
- Se utilizaron modelos de trasplante de microbiota fecal para estudiar el desarrollo de la disbiosis y las intervenciones terapéuticas en la colitis.
Principales resultados:
- Se identificaron metabolitos asociados a la microbiota (taurina, histamina, espermina) como moduladores clave del inflamatorio NLRP6 y de la secreción epitelial de IL-18.
- La deficiencia de inflamasoma condujo a un paisaje de AMP distorsionado, promoviendo la disbiosis.
- La microbiota inductora de colitis suprimió la actividad inflamatoria a través de metabolitos, alterando el equilibrio de AMP para favorecer su colonización.
- La restauración del eje metabolito-inflamatorio-AMP mejoró la colitis y normalizó la microbiota intestinal.
Conclusiones:
- Los metabolitos microbianos juegan un papel crítico en la configuración de la interfaz huésped-microbioma a través de la modulación inmune innata.
- El eje metabolito-inflamatorio-AMP identificado es esencial para mantener la estabilidad de la comunidad microbiana.
- Las intervenciones metabólicas dirigidas (postbióticos) son prometedoras para el tratamiento o la prevención de enfermedades relacionadas con la disbiosis.
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