Altered gut microbiota and short-chain fatty acid in acute ischaemic stroke with active cancer.

Background: Acute ischaemic stroke (AIS) in patients with active cancer presents unique etiological factors and correlates with worse outcomes. Although gut microbiota dysbiosis has been separately documented in stroke pathophysiology and cancer progression, gut microbial profiles in patients with concurrent conditions remain unexplored. We investigated gut microbiota composition and short-chain fatty acid (SCFA) levels in patients with AIS and active cancer.

Methods: In this prospective observational study, we analysed consecutive patients with AIS admitted between 2018 and 2023. Gut microbiota profiles were characterised using 16S rRNA sequencing. Faecal SCFAs were quantified by gas chromatography-mass spectrometry, and serum biomarkers of intestinal barrier function were measured. Functional outcomes were assessed using the modified Rankin Scale (mRS) at 180 days poststroke.

Results: Among 942 consecutive AIS patients, 156 met inclusion criteria: 42 with active cancer and 114 matched controls. Patients with concurrent AIS and cancer demonstrated significant taxonomic alterations, characterised by elevated Firmicutes-to-Bacteroidetes ratio (F/B: 1.2 vs 0.6; p=0.010) and Clostridiales-to-Bacteroidales ratio (C/B: 1.1 vs 0.6; p=0.008) compared with controls. These patients exhibited enrichment of inflammation-associated bacteria, depletion of SCFA-producing microbes, reduced faecal SCFA levels and elevated markers of intestinal barrier dysfunction (all p<0.05). The abundance of inflammation-associated genera Erysipelotrichaceae and Dorea correlated with elevated D-dimer levels and worse 180-day mRS scores. Multivariate analysis identified Clostridiales abundance, F/B and C/B ratios as independent predictors of poor functional outcomes (mRS≥3) at 180 days.

Conclusions: Patients with concurrent AIS and active cancer demonstrate distinct gut microbiota profiles and reduced SCFA production, associated with compromised intestinal barrier function and poor outcomes. These observations suggest perturbed gut-brain axis function and motivate exploratory research into microbiota-targeted approaches for this high-risk population.