Sodium oligomannate (GV-971) attenuates post-stroke cognitive impairment by restoring intestinal butyrate metabolism
In a murine ischemic stroke model, GV-971 favored cognition and restored butyrate-producing bacteria, but causal evidence in humans is absent.
| Population | Human PSCI patients (observational cohort) and tMCAO mice of both sexes (experimental model) |
|---|---|
| Intervention | Oral GV-971; butyrate supplementation in vitro |
| Comparator | Non-stroke controls (humans); untreated tMCAO animals; antibiotics and fecal microbiota transplantation as mechanistic controls |
| Outcome | Cognitive performance (tMCAO murine model); Fecal butyrate levels (human PSCI); AUC of PSCI predictive model; Hippocampal microglial activation (murine); Butyrate-mediated HDAC3 inhibition (in vitro, HT22); LPS-induced inflammatory response (in vitro, BV2); Hippocampal neurogenesis (murine) |
Summary of findings
| Outcome | Effect | 95% CI | Certainty | Clinical relevance | Notes |
|---|---|---|---|---|---|
| Cognitive performance (tMCAO murine model) | effect size not reported; direction favorable for GV-971 vs untreated tMCAO, sex-independent | — | Low | — | 1 studies |
| Fecal butyrate levels (human PSCI) | significantly reduced vs controls; exact values and 95% CI not reported in available text | — | Low | — | 1 studies |
| AUC of PSCI predictive model | AUC 0.793 internal, 0.795 external validation; 95% CI not reported | — | Low | — | 1 studies |
| Hippocampal microglial activation (murine) | reduced by GV-971 vs untreated tMCAO; quantitative effect size not reported in available text | — | Low | — | 1 studies |
| Butyrate-mediated HDAC3 inhibition (in vitro, HT22) | significant inhibition of HDAC3 enzymatic activity; IC50 or 95% CI not reported in available text | — | Very low | — | 1 studies |
| LPS-induced inflammatory response (in vitro, BV2) | attenuated by butyrate vs LPS alone; quantitative effect size not reported in available text | — | Very low | — | 1 studies |
| Hippocampal neurogenesis (murine) | promoted by elevated butyrate via Ac-H3K9/K14; quantitative effect size not reported in available text | — | Low | — | 1 studies |
Context
Post-stroke cognitive impairment (PSCI) affects 33–50% of stroke survivors and lacks approved disease-modifying pharmacotherapy. Post-stroke gut dysbiosis with depletion of butyrate producers is a candidate mechanism. GV-971 is a marine algae-derived oligosaccharide approved in China for Alzheimer's disease.
What the study showed
PSCI patients had significantly reduced fecal butyrate correlated with cognitive scores. The machine learning model achieved AUC 0.793 (internal) and 0.795 (external validation). In tMCAO mice, GV-971 restored butyrate-producing bacteria, reduced microglial activation, and improved cognitive performance sex-independently. In vitro, butyrate inhibited HDAC3 activity in HT22 cells and attenuated LPS-induced inflammation in BV2 microglia.
How it was done
Mixed-design study: observational cohort of PSCI patients (exact n not specified in provided text) for butyrate-cognition correlation and predictive model construction; tMCAO murine model with metagenomic analysis, fecal microbiota transplantation, and antibiotic depletion; in vitro experiments in HT22 and BV2 cells. Duration of murine experiments not specified in the abstract.
Effect magnitude
Predictive model AUC: 0.793–0.795; specific effect sizes (OR, SMD, 95% CI) for cognitive and molecular outcomes not reported in the provided text.
Risk of bias
The human component is strictly observational, precluding causal inference between butyrate and PSCI. Human sample size is not described in the available excerpt. Translation from tMCAO murine model to human PSCI faces well-known structural limitations. Formal risk-of-bias tools (RoB 2, ROBINS-I) are not mentioned.
What this study does NOT prove
This study does not prove that GV-971 improves cognition in humans with PSCI, nor that butyrate restoration is an obligatory causal mechanism in humans. Murine data are not directly generalizable to clinical practice.
In clinical practice
No change in clinical practice is justified based on this single study. Clinicians should not prescribe GV-971 for PSCI outside clinical trial settings. Fecal butyrate monitoring as a PSCI biomarker lacks prospective clinical validation.
Limitations
The human component is strictly observational, precluding causal inference between butyrate and PSCI. Human sample size is not described in the available excerpt. Translation from tMCAO murine model to human PSCI faces well-known structural limitations. Formal risk-of-bias tools (RoB 2, ROBINS-I) are not mentioned.
What is still missing
RCT in humans with PSCI testing GV-971 with primary cognitive outcomes and butyrate as an intermediate biomarker. Dose-response and long-term safety studies in diverse populations.
Technical appendix
Version history
- 1.0 · 2026-07-12 — Auto-generated under Evidence Standard v1.0