Influence of the Gut Microbiota on Acute Ischemic Stroke Functional Outcomes at Three Months
Lledós, Miquel (Universitat de Barcelona)
Prats-Sánchez, Luis Antonio (Institut de Recerca Sant Pau)
Muiño, Elena (Institut de Recerca Sant Pau)
Cullell, Natalia (Mútua Terrassa)
Llucià-Carol, Laia (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Cárcel-Márquez, Jara (Institut de Recerca Sant Pau)
Gallego-Fabrega, Cristina (Institut de Recerca Sant Pau)
Martín-Campos, Jesús María (Institut de Recerca Sant Pau)
Marín, Rebeca (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Aguilera-Simón, Ana (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Guasch-Jiménez, Marina (Institut de Recerca Sant Pau)
Ezcurra Diaz, Garbiñe (Institut de Recerca Sant Pau)
Camps-Renom, Pol (Institut de Recerca Sant Pau)
Martí-Fàbregas, Joan (Institut de Recerca Sant Pau)
Fernández Cadenas, Israel (Institut de Recerca Sant Pau)
Freijo, María del Mar (Hospital Universitario de Cruces (Barakaldo, País Basc))
Universitat Autònoma de Barcelona. Departament de Medicina

Date:	2025
Abstract:	Background: Functional recovery from ischemic stroke (IS), the main cause of adult disability worldwide, is influenced by many factors, and a portion of interindividual variability remains unexplained. Methods: Observational study in a tertiary stroke centre of patients with IS analyzed using shotgun metagenomic sequencing (January 2020-March 2022). Functional outcomes were assessed according to modified Rankin Scale (mRS) scores 3-months post-IS, considering 0-2 favorable and 3-6 unfavorable. The causal relationship between several bacteria and post-IS outcomes was explored via two-sample Mendelian randomization (MR) analyses using Genome-Wide Association Analysis (GWAS) summary statistics. Results: Comparing 128 patients with favorable and unfavorable post-IS functional outcomes, β-diversity analysis showed a separation in microbial structure, and α-diversity measures revealed greater bacterial richness in the favorable outcomes group. Taxonomic profiling of the samples showed that a greater abundance of pathogenic bacteria (e. g. , Pseudomonas, Finegoldia, Porphyromonas) was associated with an unfavorable outcome. Functional profiling of the samples revealed differences in the ethylbenzene degradation pathway and in 16S rRNA (uracil1498-N3)-methyltransferase. MR confirmed increased pyruvate levels to be causally associated with post-IS favorable outcomes (β = -0. 50, 95% CI: -0. 91, -0. 10). Conclusions: Our study points to gut microbiota differences in patients with unfavorable versus favorable 3-month post-IS outcomes. Patients with unfavorable outcomes presented gut microbiota dysbiosis and alterations in multiple metabolic pathways. Trial Registration: This study was registered on 3 October 2021 with https://clinicaltrials. gov. Access number: NCT04795687.
Grants:	Instituto de Salud Carlos III PI18/01338 Instituto de Salud Carlos III AC19/00106 Instituto de Salud Carlos III PI20/00925
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Functional outcome ; Gut-brain axis ; Ischemic stroke ; Microbiota ; Shotgun metagenomics
Published in:	European Journal of Neurology, Vol. 32, Num. 7 (July 2025) , art. e70265, ISSN 1468-1331

DOI: 10.1111/ene.70265
PMID: 40686474

11 p, 1022.6 KB

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