Integration of Gut Microbiota, Stroke Dysbiosis Index, And Inflammatory Biomarkers in Assessing Prognosis of Acute Ischemic Stroke

Weny Rinawati^1,2Aryati Aryati^3,4Abdulloh Machin^4,5*Stefan Kiechl^6,7Gregor Broessner⁸

• ¹Faculty of Medicine, Airlangga University, Surabaya, Indonesia
• ²Rumah Sakit Pusat Otak Nasional Dr Mahar Mardjono, Jakarta, Indonesia
• ³Universitas Airlangga Departemen Patologi Klinik, Surabaya, Indonesia
• ⁴RSUD Dr Soetomo, Surabaya, Indonesia
• ⁵Universitas Airlangga Departemen Neurologi, Surabaya, Indonesia
• ⁶Landeskrankenhaus Innsbruck Department Neurologie und Neurochirurgie, Innsbruck, Austria
• ⁷VASCage - Center for Clinical Stroke Research, Innsbruck, Austria, Innsbruck, Austria
• ⁸University of innsbruck departmemt unair, Penn State Health Department of Neurology, Hershey, United States

Background: Acute ischemic stroke (AIS) is often complicated by systemic infections that worsen prognosis. Emerging evidence suggests gut microbiota dysbiosis, inflammatory biomarkers, and gut–barrier dysfunction play pivotal roles in post-stroke outcomes. This study aimed to integrate Stroke Dysbiosis Index (SDI), Microbial Dysbiosis Index (MDI), and inflammatory biomarkers to evaluate their prognostic value in AIS patients. Methods: An observational prospective cohort was conducted at a tertiary stroke center in Jakarta (September 2023–September 2024). Eighty AIS patients admitted within 24 hours of onset were enrolled. Fecal samples underwent 16S rRNA sequencing for microbiota profiling and SDI/MDI calculation. Blood biomarkers (NMDAR-Ab, butyrate, TMAO, RANKL, iFABP, LPS) and platelet-to-lymphocyte ratio (PLR) were measured. Clinical severity was assessed with NIHSS. Outcomes included infection within 7 days, in-hospital mortality, and complications. Statistical analyses comprised correlation, regression, and ROC curve modeling. Results: Infection occurred in 46.3% of patients, predominantly older (>60 years) and female. Infected patients showed reduced microbial diversity, enrichment of pathogenic taxa (Klebsiella, Escherichia, Salmonella), elevated SDI/MDI, and depleted SCFA producers. Biomarkers revealed increased NMDAR, TMAO, iFABP, and LPS, with reduced butyrate and RANKL (all p < 0.001). These markers correlated strongly with infection status. ROC analysis demonstrated promising discriminative ability in this cohort (bias-corrected AUCs > 0.80 after internal bootstrapping validation). Internal validation using 1000 bootstrap resamples was performed to estimate optimism in AUC values and obtain bias-corrected confidence intervals. Conclusion: Gut dysbiosis, elevated dysbiosis indices, and inflammatory biomarker derangements were strongly associated with post-stroke infections and adverse prognosis. Integrating microbiota and biomarker profiles with clinical parameters may provide a robust framework for risk stratification and open avenues for microbiota-targeted therapies in AIS.