Stroke is a leading cause of death and disability worldwide. As neuroprotective approaches have been shown to be insufficient when managing the condition, scientists have started focusing on alternative targets such as the gut microbiota. Interestingly, changes in gut microbiota composition have been reported as having an influence on many risk factors for stroke such as hypertension, type 2 diabetes, obesity, atherosclerosis, aging and vascular dysfunction.
However, the interactions between gut microbiota and stroke outcomes remain largely unknown.
A new prospective observational study, carried out by researchers from the Nanfang and Zhujiang Hospitals at Southern Medical University in China, reveals a link between altered short-chain fatty acid-producing bacteria and poor functional outcomes in patients diagnosed with acute ischemic stroke.
The authors explored whether changes in fecal microbiota composition and short-chain fatty acid levels in adult patients diagnosed with acute ischemic stroke and healthy controls were related to poor functional outcomes at 90 days.
The fecal microbiota allowed scientists to distinguish patients with acute ischemic stroke and healthy controls. Patterns of gut microbiota changes observed in stroke patients consisted of a lack of SCFA-producing bacteria and an increase in Lactobacillaceae and Akkermansia and opportunistic pathogens Enterobacteriaceae and Porphyromonadaceae. In line with the findings, a recent study in both patients after stroke and mice revealed stroke rapidly triggers changes in the gut microbiota, with Enterobacteriaceae overgrowth that, in turn, can exacerbate brain infarction.
Discriminative taxa at the family level allowed for distinguishing between mild, moderate and severe stroke patients. Patients with acute ischemic stroke exhibited a high Firmicutes/Bacteroidetes ratio, a lack of SCFA-producing bacteria and SCFAs. They also showed an altered intestinal barrier function, assessed according to biomarkers of intestinal barrier dysfunction—fatty acid-binding protein (FABP), d-lactate, lipopolysaccharide (LPS), and LPS-binding protein (LBP)—compared to healthy controls. More interestingly, patients with higher stroke severity showed the greatest difference in gut microbiota composition compared to healthy controls.
Further statistical analyses exploring associations between low SCFAs and 90-day poor functional outcomes showed that the abundance of the SCFA-producing bacterium Roseburia and SCFAs levels were negatively associated with stroke severity. Patients with 90-day poor functional outcomes had lower SCFA levels (especially acetate) than those without. That association persisted after taking into account other variables known to affect the gut microbiota, including age, sex, history of cardiovascular disease, dietary habits and transit time. In contrast, the populations of SCFA-producing bacteria and gut barrier function biomarkers did not correlate with functional outcomes of stroke.
On the whole, the findings suggest that changes in the levels of SCFA-producing bacteria and metabolites in patients’ stools could emerge as a potential marker for evaluating the progress of stroke and therapeutic targets for stroke. Altogether, the study supports the previously tested hypothesis that enriching the gut microbiota of patients with stroke with SCFA could be worth considering.
Durgan DJ, Lee J, McCullough LD, et al. Examining the role of the microbiota-gut-brain axis in stroke. Stroke. 2019; 50(8):2270-2277. doi: 10.1161/STROKEAHA.119.025140.
Tan C, Wu Q, Wang H, et al. Dysbiosis of gut microbiota and short-chain fatty acids in acute ischemic stroke and the subsequent risk for poor functional outcomes. JPEN J Parenter Enteral Nutr. 2021; 45(3):518-529. doi: 10.1002/jpen.1861.
Xu K, Gao X, Xia G, et al. Rapid gut dysbiosis induced by stroke exacerbates brain infarction in turn. Gut. 2021. doi: 10.1136/gutjnl-2020-323263.
Chen R, Xu Y, Wu P, et al. Transplantation of fecal microbiota rich in short chain fatty acids and butyric acid treat cerebral ischemic stroke by regulating gut microbiota. Pharmacol Res. 2019; 148:104403. doi: 10.1016/j.phrs.2019.104403.