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Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/212602
Caracterización de la microbiota intestinal en pacientes con ictus isquémico: un estudio metagenómico
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[spa] Esta tesis investiga la asociación de la microbiota intestinal con el ictus isquémico. Se reclutaron un total de 340 pacientes con ictus, de los cuales se analizó una muestra fecal para obtener un perfil taxonómico y funcional detallado de la microbiota intestinal de cada sujeto. De este modo, encontramos que los hombres con ictus tenían una mayor riqueza bacteriana en comparación con las mujeres. Además, también observamos diferencias entre sexos en los niveles de Fusobacteriaceae. Mediante el uso de herramientas bioinformáticas para determinar la causalidad entre los taxones y el riesgo de ictus, utilizamos datos genéticos de más de 1 millón de sujetos para realizar análisis de aleatorización Mendeliana. Estos indicaron que los niveles de Fusobacteriaceae se asociaban causalmente con un mayor riesgo de ictus isquémico.
Centrándonos en la fase crónica, encontramos que existía una clara separación entre las comunidades bacterianas entre aquellos pacientes con buena o mala evolución funcional a los 3 meses tras el ictus medida con la Escala de Rankin modificada (mRS, de ‘modified Rankin Scale’), y observamos que el grupo con buena evolución presentaba una mayor riqueza bacteriana. Además, también encontramos mayores niveles de bacterias patógenas oportunistas (p. ej., Pseudomonas, Finegoldia), así como cambios en la actividad de la vía de degradación del etilbenceno y de la enzima ARNr 16S (uracil1498- N3)-metiltransferasa, en aquellos pacientes con una mala evolución.
Finalmente, enfocándonos en la fase aguda, encontramos una separación en la estructura microbiana en función de la severidad del ictus medida con la Escala de Ictus del Instituto Nacional de Salud (NIHSS, de ‘National Institute of Health Stroke Scale’). Además, se utilizó un modelo de ratón con oclusión de la arteria cerebral media para explorar la relación causal entre la disbiosis intestinal y el volumen del infarto. Los resultados revelaron que la diversidad bacteriana, así como múltiples taxones y vías específicas, cambiaban en función de la severidad del ictus y la evolución neurológica durante las primeras 24 horas postictus. En concreto, observamos que los taxones Actinobacteria, Phascolarctobacterium, Roseburia, Parabacteroides y Porphyromonadaceae y el metabolismo de la glucosa podían ser mediadores de las alteraciones neurológicas durante la fase aguda del ictus.
[eng] This thesis investigates the association of gut microbiota with ischaemic stroke. A total of 340 patients with stroke were recruited and a faecal sample was analysed to obtain a detailed taxonomic and functional profile of the gut microbiota of each subject. Thus, we found that men with stroke had a higher bacterial richness compared to women. In addition, we also observed sex differences in Fusobacteriaceae levels. Using bioinformatics tools to determine causality between taxa and stroke risk, we used genetic data from more than 1 million subjects to perform Mendelian randomization analyses. These indicated that Fusobacteriaceae levels were causally associated with an increased risk of ischemic stroke. Focusing on the chronic phase, we found that there was a clear separation between the bacterial communities in those patients with good or poor functional outcome at 3 months after stroke measured with the modified Rankin Scale (mRS), and we observed that the group with good outcome had a higher bacterial richness. In addition, we also found higher levels of opportunistic pathogenic bacteria (e.g., Pseudomonas, Finegoldia), as well as changes in the activity of both the ethylbenzene degradation pathway and the 16S rRNA (uracil1498-N3)-methyltransferase, in those patients with a poor outcome. Finally, focusing on the acute phase, we found a separation in microbial structure according to stroke severity as measured by the National Institute of Health Stroke Scale (NIHSS). Moreover, a middle cerebral artery occlusion mouse model was used to explore the causal relationship between gut dysbiosis and infarct volume. The results revealed that bacterial diversity, as well as multiple specific taxa and pathways, changed according to stroke severity and neurological evolution during the first 24 hours poststroke. Among the results that stood out, we observed that the taxa Actinobacteria, Phascolarctobacterium, Roseburia, Parabacteroides, Porphyromonadaceae, and glucose metabolism could be mediators of neurological alterations during the acute phase of stroke.
[eng] This thesis investigates the association of gut microbiota with ischaemic stroke. A total of 340 patients with stroke were recruited and a faecal sample was analysed to obtain a detailed taxonomic and functional profile of the gut microbiota of each subject. Thus, we found that men with stroke had a higher bacterial richness compared to women. In addition, we also observed sex differences in Fusobacteriaceae levels. Using bioinformatics tools to determine causality between taxa and stroke risk, we used genetic data from more than 1 million subjects to perform Mendelian randomization analyses. These indicated that Fusobacteriaceae levels were causally associated with an increased risk of ischemic stroke. Focusing on the chronic phase, we found that there was a clear separation between the bacterial communities in those patients with good or poor functional outcome at 3 months after stroke measured with the modified Rankin Scale (mRS), and we observed that the group with good outcome had a higher bacterial richness. In addition, we also found higher levels of opportunistic pathogenic bacteria (e.g., Pseudomonas, Finegoldia), as well as changes in the activity of both the ethylbenzene degradation pathway and the 16S rRNA (uracil1498-N3)-methyltransferase, in those patients with a poor outcome. Finally, focusing on the acute phase, we found a separation in microbial structure according to stroke severity as measured by the National Institute of Health Stroke Scale (NIHSS). Moreover, a middle cerebral artery occlusion mouse model was used to explore the causal relationship between gut dysbiosis and infarct volume. The results revealed that bacterial diversity, as well as multiple specific taxa and pathways, changed according to stroke severity and neurological evolution during the first 24 hours poststroke. Among the results that stood out, we observed that the taxa Actinobacteria, Phascolarctobacterium, Roseburia, Parabacteroides, Porphyromonadaceae, and glucose metabolism could be mediators of neurological alterations during the acute phase of stroke.
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LLEDÓS I DE BENITO, Miquel. Caracterización de la microbiota intestinal en pacientes con ictus isquémico: un estudio metagenómico. [consulted: 12 of August of 2026]. Available at: https://hdl.handle.net/2445/212602