Polyphenol-Mediated Microbiome Modulation in STEMI Patients: a Pilot Study

Argul Issilbayeva^1*Shynggys Sergazy¹Azamat Zhashkeyev²Alexander Gulyayev¹Samat Kozhakhmetov¹Zarina Shulgau¹Madiyar Nurgaziyev¹Ayaulym Nurgozhina¹Sanzhar Zhetkenev¹Nurislam Mukhanbetzhanov¹Zharkyn Jarmukhanov¹Zhanel Mukhanbetzhanova¹Elizaveta Vinogradova¹Zhaxybay Zhumadilov³Almagul Kushugulova¹Mohamad Aljofan^1,4

• ¹National Laboratory Astana, Nazarbayev University, Nur-Sultan, Kazakhstan
• ²Karaganda Medical University, Karaganda, Kazakhstan
• ³Department of Surgery, School of Medicine, Nazarbayev University, Astana, Kazakhstan
• ⁴Department of Biomedical Sciences, School of Medicine, Nazarbayev University, Nur-sultan, Kazakhstan

This study investigates the effects of polyphenol supplementation on gut microbiome composition and cardiovascular health in patients with ST-segment elevation myocardial infarction (STEMI). Methods: Double-blind randomized control trial where participants received either polyphenol supplementation or placebo for three months, after which composition of the gut microbiome; clinical and laboratory parameters, including TMAO levels and oxidative stress levels, were assessed. Results: The stable TMAO levels (from 0.5[0.2-0.9] to 0.4[0.3-0.9] μmol, p>0.05) were observed in the polyphenol group, compared to the increase observed in the placebo group (from 0.5[0.3-0.6] to 0.7[0.5-1.4]) μmol, p<0.001). Polyphenol supplementation significantly decreased the Firmicutes/Bacteroidetes ratio (p=0.04) and increased beneficial bacteria such as Roseburia (p=0.01), Agathobaculum sp. (p=0.004), Alistipes finegoldii (p=0.04) and Sellimonas (p=0.002). Predicted metabolic pathways analysis supports potential mechanisms linking polyphenol intake to microbiome modulation and TMAO regulation. Conclusion: Our findings demonstrate that polyphenol supplementation maintains stable TMAO levels by restructuring gut microbiome composition in STEMI patients, evidenced by a more focused microbiome with a significant increase in beneficial butyrate-producing bacteria (Roseburia, Agathobaculum sp., Alistipes finegoldii, and Sellimonas) and a decreased Firmicutes/Bacteroidetes ratio, suggesting microbiome-mediated cardioprotective effects. While promising, our preliminary findings require further studies with larger cohorts and more advanced sequencing methods to establish their significance for cardiovascular health.