Gut-Brain Axis Links Gastrointestinal Syndromes to Ischemic Stroke Risk

Background It has been hypothesized that the gut microbiome affects ischemic stroke occurrence. However, the relationship between stroke and GI disorders is not well understood. We aimed to determine whether GI syndromes are associated with an increased risk of ischemic stroke. Methods We conducted case‐control and cohort studies using the TriNetX US Collaborative Network database (2018‐2022). In the case‐control study, patients with ischemic stroke were compared to propensity‐score‐matched controls with at least 3 years of prior data. The cohort study assessed the risk of stroke in patients with specific GI syndromes over 5 years compared to matched controls. Results For the case‐control study, 551,738 patients with ischemic stroke were matched with 19,419,979 negative controls, resulting in 548,179 pairs after matching. Compared to matched negative controls, all GI syndromes, appendectomy, and GI medications were significantly associated with ischemic stroke (all p<0.001). In the cohort study, all GI syndromes were significantly associated with ischemic stroke (all RR>1, p<0.001), but appendectomy was not (RR 1.28, 95% CI: 0.89‐1.82). Conclusion Several GI disorders were associated with an increased risk of future ischemic stroke, providing more evidence on the gut‐brain axis. Further research is warranted to confirm these findings and investigate underlying mechanisms.