Integrated Oral Microbiome and Metabolome Analysis Unveils Key Biomarkers and Functional Pathway Alterations in Patients with Acute Myocardial Infarction

Ikram Khan^1*Muhammad Irfan²Imran Khan³Xie Ping^4,5Yu Xiaohui⁶Shengnan Lei⁷Tianzhu Song⁷Xiaodong Xie⁸Li Zhiqiang⁷

• ¹School of Basic Medical Sciences, Lanzhou University, Lanzhou, China
• ²Khyber Medical University, Peshawar, Khyber Pakhtunkhwa, Pakistan
• ³Dalian Medical University, Dalian, Liaoning, China
• ⁴Second Provincial People’s Hospital of Gansu, Lanzhou, Gansu Province, China
• ⁵Third People's Hospital of Gansu Province, Lanzhou, Gansu Province, China
• ⁶The 940 Hospital Joint Logistic Support Force of PLA, Lanzhou, Gansu Province, China
• ⁷Northwest University for Nationalities, Lanzhou, Gansu Province, China
• ⁸Lanzhou University, Lanzhou, Gansu Province, China

The significance of oral microbiota in acute myocardial infarction (AMI) has been increasingly appreciated. However, the association between oral microbiota, metabolites, and AMI parameters, as well as the key microbiota and metabolites that may play a crucial role in this process, remains unclear. To investigate the oral microbiome composition and metabolomic profiles associated with AMI and explore the roles of specific bacterial species and key metabolites in functional pathways in the progression of AMI. A case-control study was conducted involving 24 AMI patients and 24 matched healthy controls. Saliva samples were collected for 16S rRNA sequencing and untargeted LC-MS metabolomics. Correlation analysis was then conducted to explore associations between microbial taxa, metabolomic profiles, and AMI clinical parameters, with results visualized as heatmaps of correlation coefficients. The component of the oral microbiota of the AMI group showed significant alterations when compared to the control group. Particularly, a significant shift in terms of alpha and beta diversity was observed between the AMI and control groups (p < 0.05). Streptococcus and Rothia genera and 9(R)-HODE, 20-HETE ethanolamide, and 5,6 EET metabolites were identified as potential biomarkers, achieving an area under the curve of 0.82-0.88. Functional pathway analysis demonstrated significant upregulation in key metabolic pathways, including the Citrate Cycle (TCA cycle), Pyruvate metabolism, and Glucagon signaling pathways, which exhibited strong correlations with established clinical markers of AMI. This integrative analysis underscores the diagnostic potential of oral microbiome-metabolome interactions in AMI and unveils key mechanistic pathways for guiding future therapeutic interventions.