Objective It has been hypothesized that intracranial aneurysm (IA) formation and rupture are affected by the gut microbiome, but research is still limited. This study sought to determine the prevalence of gastrointestinal (GI) syndromes and interventions preceding the diagnosis of IA in comparison to negative controls (NCs).

Methods Utilizing the TriNetX Research Network, a nationwide US-based database (October 1, 2015, to October 1, 2023), we conducted both a case-control and cohort study. In the case-control analysis, patients diagnosed with unruptured IA were compared with propensity-score-matched NCs, as were those with ruptured IA. Additionally, ruptured IA patients were compared with matched unruptured IA cases. To validate findings, a cohort study was conducted, comparing cohorts exposed to various GI syndromes with matched NCs for the development of unruptured and ruptured IAs within a five-year timeframe.

Results Our analysis identified 72,545 unruptured and 46,748 ruptured IA patients for the case-control examination. In comparison to matched NCs, all GI syndromes and appendectomy were significantly associated with both ruptured and unruptured IAs (all p<0.001). Ruptured IAs demonstrated significant associations with a history of all diseases of the digestive system (ICD-10: K00-K95), dysphagia, diarrhea, and constipation when contrasted with matched unruptured IA cases. Conversely, unruptured IAs exhibited significant associations with a history of gastroesophageal reflux disease (GERD), functional dyspepsia, and irritable bowel syndrome without diarrhea. In the cohort study, dysphagia, diarrhea, constipation, gastroparesis, and fecal incontinence displayed significant associations with both ruptured and unruptured IAs (OR>1; p<0.05). GERD, functional dyspepsia, and irritable bowel syndrome (IBS) without diarrhea were only associated with unruptured IAs.

Conclusion History of dysphagia, diarrhea, and constipation are associated with both the formation and rupture of IAs, while GERD, functional dyspepsia, and IBS without diarrhea are associated with IA formation only. Further studies are warranted to elucidate these associations and explore the intricate interplay among GI syndromes, the gut microbiome, and IA pathogenesis.

Disclosures G. Sioutas: None. M. Salem: None. O. Shekhtman: None. V. Srinivasan: None. J. Burkhardt: None.