ORIGINAL RESEARCH article
Front. Med.
Sec. Pathology
Diagnostic Value of Gut Microbiota Profiling and Circulating Biomarkers to Predict Post-Stroke Infection in Acute Ischemic Stroke
Weny Rinawati 1,2
Aryati Aryati 3,4
Abdulloh Machin 4,5,6
Stefan Kiechl 7,8
Gregor Broessner 7
1. Faculty of Medicine, Airlangga University, Surabaya, Indonesia
2. Rumah Sakit Pusat Otak Nasional Dr Mahar Mardjono, Jakarta, Indonesia
3. Universitas Airlangga Departemen Patologi Klinik, Surabaya, Indonesia
4. Universitas Dr Soetomo, Surabaya, Indonesia
5. Universitas Airlangga Departemen Neurologi, Surabaya, Indonesia
6. Rumah Sakit Universitas Airlangga, Surabaya, Indonesia
7. Landeskrankenhaus Innsbruck Department Neurologie und Neurochirurgie, Innsbruck, Austria
8. VASCage - Center for Clinical Stroke Research, Innsbruck, Austria
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Abstract
Background: Post-stroke infection (PSI), particularly pneumonia and urinary tract infection, is a common and serious complication after acute ischemic stroke (AIS). Current diagnostic biomarkers provide limited accuracy when used in isolation. This study aimed to evaluate the diagnostic value of circulating biomarkers and gut microbiota profiling, both individually and in combination, to predict PSI in AIS patients. Methods: We conducted a prospective observational study at Prof. Dr. dr. Mahar Mardjono National Brain Center Hospital, Jakarta. 80 AIS patients admitted within 24 hours of onset were enrolled and followed for 7 days to assess PSI. Blood samples were analyzed for NMDAR, butyrate, TMAO, RANKL, iFABP, and LPS. Stool samples were collected for 16S rRNA sequencing. Diagnostic performance was evaluated using ROC curves, with AUC, sensitivity, and specificity calculated. Multivariate logistic regression models were constructed to assess independent predictors and combined diagnostic accuracy. Results: PSI occurred in 37/80 patients (46.3%). NMDAR showed the highest diagnostic performance (AUC 0.911; sensitivity 86.5%; specificity 90.7), followed by iFABP (AUC 0.894), LPS (AUC 0.896), RANKL (AUC 0.881), butyrate (AUC 0.866), and TMAO (AUC 0.865). Gut microbiota analysis revealed reduced evenness and dominance imbalance in infected patients, with enrichment of pathogenic taxa (Escherichia coli, Salmonella enterica) and depletion of SCFA-producing commensals (Faecalibacterium prausnitzii, Roseburia intestinalis). Multivariate models integrating microbiota features and biomarkers improved predictive accuracy compared with single-domain approaches. Conclusion: Integrating circulating biomarkers with gut microbiota profiling significantly enhances early prediction of PSI in AIS. These findings highlight the role of the gut–brain–immune axis in post-stroke complications and support combined biomarker–microbiota models for risk stratification and preventive strategies.
Summary
Keywords
Acute ischemic stroke, post-stroke infection, biomarkers, Gut Microbiota, Diagnostic accuracy
Received
09 September 2025
Accepted
05 December 2025
Copyright
© 2025 Rinawati, Aryati, Machin, Kiechl and Broessner. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Aryati Aryati; Abdulloh Machin
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