Ischemic Stroke Risk May Increase in Individuals With Specific Gut Microbiome

Specific gut microbiome bacteria may have an effect on the risk for subtypes of ischemic stroke, according to study findings published in the European Journal of Preventive Cardiology.

The relationship between the gut microbiome and the onset of ischemic stroke has generated controversy. It is well known that “gut dysbiosis directly results in some conditions that are risk factors for stroke,” including hypertension, diabetes, vascular dysfunction, dyslipidemia, obesity, and aging. It remains to be elucidated, however, whether only 1 or multiple bacterial entities are responsible for the various subtypes of ischemic stroke.

Researchers conducted a 2-sample Mendelian Randomization (MR) analysis to assess the relationship between specific gut microbiome and subtypes of ischemic stroke, including cardioembolic, small vessel, and large artery stroke. They also sought to propose possible strategies for the prevention of stroke.

The MR study used single-nucleotide polymorphisms (SNPs) to evaluate the causal effect between exposure and outcomes. Summary data were based primarily on independent genome-wide association studies (GWAS) of 18,340 individuals from 24 population-based cohorts. Exposure data were obtained from the international consortium MiBioGen, which was established in an effort to explore the impact of human genetics on gut microbiome.

A total of 194 bacterial traits that contained the following 5 biological levels were included:

• Phylum
• Class
• Order
• Family
• Genus

Researchers found that among the 194 gut bacterial features evaluated, the majority were not associated with subtypes of ischemic stroke. Overall, the following 4 bacterial features were potentially associated with an increased risk for large artery stroke:

• Phylum_Proteobacteria: odds ratio (OR), 1.66; 95% CI, 1.02-2.70
• Family_Pasteurellaceae: OR, 1.34; 95% CI, 1.05-1.71
• Genus_Gordonibacter: OR, 1.36; 95% CI, 1.05-1.76
• Genus_Fusicatenibacter: OR, 1.42; 95% CI, 1.02-1.97

In contrast, 5 bacterial features were significantly associated with a lower risk for large artery stroke in the primary inverse variance weighted (IVW)-MR analysis (P <.05):

• Order_Rhodospirillales: OR, 0.78; 95% CI, 0.62-0.98
• Genus_Tyzzerella3: OR, 0.81; 95% CI, 0.68-0.97
• Genus_Intestinimonas: OR, 0.77; 95% CI, 0.61-0.98
• Genus_RuminococcaceaeUCG009: OR, 0.73; 95% CI, 0.56-0.95
• Genus_Methanobrevibacter: OR, 0.70; 95% CI, 0.54-0.91

Per MR estimates of weighted median, however, 4 bacterial species were shown to be significantly associated with risk for large artery stroke:

• Family_Pasteurellaceae: OR, 1.45; 95% CI, 1.05-2.02
• Genus_RuminococcaceaeUCG009: OR, 0.68; 95% CI, 0.49-0.94
• Genus_Methanobrevibacter: OR, 0.71; 95% CI, 0.51-0.99
• Genus_Intestinimonas: OR, 0.72; 95% CI, 0.53-0.99

Overall, 4, 3, and 4 bacteria demonstrated an increased risk for large artery stroke, small vessel stroke, and cardioembolic stroke, respectively, whereas 5, 6, and 5 bacteria were associated with a decreased risk for large artery stroke, small vessel stroke, and cardioembolic stroke, respectively.

Of these bacteria, the Intestinimonas demonstrated negative correlations with large artery stroke (OR, 0.77; 95% CI, 0.61-0.98) and small vessel stroke (OR, 0.85; 95% CI, 0.73-0.98). Further, the Lachnospiraceae NK4A136 group was genetically linked to a decreased risk for both small vessel stroke (OR, 0.81; 95% CI, 0.66-0.99) and cardioembolic stroke (OR, 0.75; 95% CI, 0.60-0.94).

Limitations regarding the use of MR for the selection of gut microbiome should be noted. With recognition that the abundance of gut microbiome potentially may be impacted by diet, medication, gender, and time of sampling, the variance supported by genetics may decrease. In addition, because different cohorts were used, nonlinear associations could not be verified.

“This Mendelian randomization study supports the causal effects of the gut microbiome on ischemic stroke. Several types of intestinal bacterial traits were detected to potentially increase or decrease the risk of incident ischemic stroke. These may have prospects for the prevention of different ischemic stroke subtypes. In addition, the clinical benefits of the gut microbiome should be further evaluated in future large-scale people research,” the researchers concluded.

This article originally appeared on Neurology Advisor