Does Infarct Size Influence Gut Barrier Integrity and Bacterial Translocation after Experimental Stroke?

Granados-Martinez, C.; ALFAGEME-LOPEZ, N.; Fernandez-Bustelo, A.; Amarilla, M. A.; Navarro-Oviedo, M.; Sevillano-Fernandez, D.; Alou-Cervera, L.; Hurtado, O.; Moro, M. A.; Lizasoain, I.; PRADILLO, J. M.

doi:10.1101/2025.11.13.688219

bioRxiv · 10.1101/2025.11.13.688219

Does Infarct Size Influence Gut Barrier Integrity and Bacterial Translocation after Experimental Stroke?

Granados-Martinez, C.·ALFAGEME-LOPEZ, N.·Fernandez-Bustelo, A.·Amarilla, M. A.·Navarro-Oviedo, M.·Sevillano-Fernandez, D.·Alou-Cervera, L.·Hurtado, O.·Moro, M. A.·Lizasoain, I.·PRADILLO, J. M.

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Abstract

BackgroundIschemic stroke (IS) triggers brain injury and systemic changes, including gut dysbiosis, intestinal barrier dysfunction (IBD), and bacterial translocation (BT). Although larger infarcts are associated with higher infection risk, it is unclear whether lesion size directly influences gut barrier integrity or bacterial dissemination. MethodsMale C57BL/6 mice underwent permanent middle cerebral artery occlusion (MCAO) proximally or distally to generate large or small infarcts. Seventy-two hours post-ischemia, infarct volume was measured by MRI, and BT was assessed in mesenteric lymph nodes, liver, spleen, and lungs. ZO-1 and MMP9 expression were used to evaluate intestinal barrier integrity. Peripheral and central inflammation were assessed by flow cytometry and immunofluorescence. ResultsProximal MCAO produced larger infarcts than distal MCAO. The proportion of animals exhibiting BT was lower in distal MCAO, but this difference was not statistically significant. ZO-1 expression did not differ between groups, while MMP9 was increased only in animals with BT, independent of infarct size. BT was associated with more pronounced lymphopenia and enhanced microglial activation and T-cell infiltration in the brain. The composition of translocated bacteria was similar across groups. ConclusionsInfarct size alone does not determine IBD or BT, although BT is linked to intestinal and cerebral inflammation. This study evaluates for the first time the effect of lesion magnitude on IBD and BT, highlighting the complex interplay between cerebral injury and gut-systemic interactions.

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Granados-Martinez, C., ALFAGEME-LOPEZ, N., Fernandez-Bustelo, A., Amarilla, M. A., Navarro-Oviedo, M., Sevillano-Fernandez, D., Alou-Cervera, L., Hurtado, O., Moro, M. A., Lizasoain, I., PRADILLO, J. M.. 2025-11-14. Does Infarct Size Influence Gut Barrier Integrity and Bacterial Translocation after Experimental Stroke?. https://doi.org/10.1101/2025.11.13.688219

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