Oral Pathobiont Streptococcus Anginosus Is Enriched in the Gut of Stroke Patients and Predicts 2-Year Cardiovascular Outcome

Abstract

Background: Several cross-sectional studies have implicated gut dysbiosis caused by an abundance of oral commensals in stroke, but the effect on long-term prognosis is still unknown. Therefore, we longitudinally investigated oral pathobionts in the gut and their clinical relevance to stroke.

Methods and Results: We analyzed the salivary and gut microbiomes collected from 189 acute stroke and 55 non-stroke subjects, and found that Streptococcus anginosus was significantly more abundant in both the saliva (median [IQR], 0.01 [0.00–0.14] vs. 0.00 [0.00–0.03], P=0.02) and gut (0.09 [0.00–0.28] vs. 0.00 [0.00–0.02], P<0.001) of the stroke patients compared with their non-stroke counterparts. Network analysis revealed S. anginosus as a central hub in gut dysbiosis. After adjusting for vascular risks, S. anginosus (odds ratio 1.20, 95% confidence interval 1.06–1.36, P<0.01), Anaerostipes hadrus (0.82, [0.73–0.93], P<0.01), and Bacteroides plebeius (0.86, [0.86–0.93], P=0.01) in the gut were independent predictors of stroke. Longitudinally, S. anginosus in the gut was significantly associated with increased rates of death and major cardiovascular events (P=0.04; log-rank test), whereas A. hadrus and B. plebeius were not (P=0.45 and P=0.19). After adjusting for vascular risks, S. anginosus in the gut was a residual risk for increased rates of death and major cardiovascular events (hazard ratio 4.78, 95% confidence interval 1.08–21.18, P=0.04)

Conclusions: S. anginosus in the gut may increase the risk of stroke and a poor prognosis.