Gut Metabolite Levels Associate with Outcomes After Aneurysmal Subarachnoid Hemorrhage

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Frontiers in Medicine Published April 9, 2026 Medically reviewed April 25, 2026 DOI ↗ By Dr. Ji-eun Park, MD · Brain, Mind & Pain

Key Takeaway

Note associations between gut metabolites and outcomes in aSAH; clinical utility remains unproven.

This prospective observational cohort study followed 80 consecutive patients with aneurysmal subarachnoid hemorrhage admitted to a tertiary neurocritical care center for 3 months. The study analyzed temporal dynamics of serum gut microbiota-derived metabolites, including short-chain fatty acids and tryptophan-related compounds, without a specific intervention or comparator. The primary outcome was functional status at 3 months assessed by the modified Rankin Scale (mRS), and delayed cerebral ischemia (DCI) was diagnosed per consensus criteria.

Lower Day 1 levels of propionic, isobutyric, and isovaleric acids were significantly associated with an unfavorable 3-month outcome (mRS 4-6). Reduced tryptophan levels at both Day 1 and Day 9, and markedly lower indole-3-propionic acid (IPA) concentrations on Day 9, were also linked to poor outcomes. For DCI, associations were observed with reduced tryptophan and propionic acid levels on both days and a pronounced decrease in IPA on Day 9. Tryptophan and propionic acid demonstrated excellent discriminative performance for outcomes, with reported AUCs up to 0.99.

In multivariable models, low Day 1 propionic acid and low Day 9 IPA independently predicted unfavorable outcome, while Day 9 tryptophan, IPA, and propionic acid independently predicted DCI. Safety and tolerability data were not reported. Key limitations include the observational design, which precludes establishing causation, and the lack of reported absolute numbers, effect sizes, or p-values/confidence intervals for most associations. The single-center setting and specific patient population also limit generalizability.

These findings position specific gut metabolites as promising associative biomarkers for secondary brain injury after subarachnoid hemorrhage. However, the evidence remains preliminary, and the clinical utility of these markers for prognosis or guiding therapy is not yet established.

Study Details

Study typeCohort

EvidenceLevel 3

PublishedApr 2026

View Original Abstract ↓

BackgroundDelayed cerebral ischemia (DCI) remains a major determinant of poor outcome after aneurysmal subarachnoid hemorrhage (aSAH). Growing evidence suggests that gut microbiota–derived metabolites, including short-chain fatty acids (SCFAs) and tryptophan-related indole compounds, modulate neuroinflammation and cerebrovascular vulnerability. However, their temporal dynamics and clinical relevance after aSAH are insufficiently characterized.MethodsIn this prospective observational study, 80 consecutive patients with aSAH were enrolled at a tertiary neurocritical care center. Serum concentrations of SCFAs (propionic, butyric, isobutyric, valeric, isovaleric, caproic acids) and tryptophan-derived metabolites (tryptophan, indole-3-propionic acid [IPA], indole-3-acetic acid, indole-3-lactic acid) were quantified using LC–MS on Day 1 and Day 9 after hemorrhage. Functional outcome at 3 months was assessed using the modified Rankin Scale (mRS), and DCI was diagnosed according to consensus criteria. Associations were analyzed using non-parametric statistics, ROC analyses, and multivariable logistic regression adjusted for established clinical confounders.ResultsPatients with unfavorable 3-month outcomes (mRS 4–6) showed significantly lower Day 1 levels of propionic, isobutyric, and isovaleric acids, persistently reduced tryptophan at both time points, and markedly lower IPA concentrations on Day 9. DCI was associated with reduced tryptophan and propionic acid levels on both days and a pronounced decrease in IPA on Day 9. Tryptophan and propionic acid demonstrated excellent discriminative performance for outcome and DCI (AUCs up to 0.99). In multivariable models, low Day 1 propionic acid and low Day 9 IPA independently predicted unfavorable outcome, while Day 9 tryptophan, IPA, and propionic acid independently predicted DCI.ConclusionDistinct temporal alterations in gut microbiota–derived metabolites after aSAH are strongly associated with functional outcome and DCI. SCFAs and tryptophan-related metabolites—particularly propionic acid, tryptophan, and IPA—emerge as promising biomarkers and potential mechanistic mediators in secondary brain injury after aSAH.

Gut Metabolite Levels Associate with Outcomes After Aneurysmal Subarachnoid Hemorrhage

Study Details

Intravenous tenecteplase improves functional outcomes but increases hemorrhage risk in non-large vessel occlusion acute ischemic stroke.

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Gut Metabolite Levels Associate with Outcomes After Aneurysmal Subarachnoid Hemorrhage

Study Details

Intravenous tenecteplase improves functional outcomes but increases hemorrhage risk in non-large vessel occlusion acute ischemic stroke.

Tenecteplase improves stroke recovery but increases bleeding risk in late treatment window

Clinical research that matters. Delivered to your inbox.

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