Alternations in gut microbiota and host transcriptome of patients with coronary artery disease

Background Coronary artery disease (CAD) is a widespread heart condition caused by atherosclerosis and influences millions of people worldwide. Early detection of CAD is challenging due to the lack of specific biomarkers. The gut microbiota and host-microbiota interactions have been well documented to affect human health. However, investigation that reveals the role of gut microbes in CAD is still limited. This study aims to uncover the synergistic effects of host genes and gut microbes associated with CAD through integrative genomic analyses. Results Herein, we collected 54 fecal and 54 blood samples from CAD patients and matched controls, and performed amplicon and transcriptomic sequencing on these samples, respectively. By comparing CAD patients with health controls, we found that dysregulated gut microbes were significantly associated with CAD. By leveraging the Random Forest method, we found that 10 bacteria biomarkers can distinguish CAD patients from health controls with a high performance (AUC = 0.939). We observed that there existed prominent associations of gut microbes with several clinical indices relevant to heart functions. Integration analysis revealed that CAD-relevant gut microbe genus Fusicatenibacter was associated with expression of CAD-risk genes, such as GBP2 , MLKL , and CPR65 . In addition, the upregulation of immune-related pathways in CAD patients were identified to be primarily associated with higher abundance of genus Blautia , Eubacterium , Fusicatenibacter , and Monoglobus . Conclusions Our results highlight that dysregulated gut microbes contribute risk to CAD by interacting with host genes. These identified microbes and interacted risk genes may have high potentials as biomarkers for CAD. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This research was funded by the Hangzhou Medical and Health Technology Project (No. Z20200135), the Construction Fund of Key Medical Disciplines of Hangzhou (No. OO20200121), the National Natural Science Foundation of China (No. 32200535), and the Scientific Research Foundation for Talents of Wenzhou Medical University (No. KYQD20201001). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was reviewed and approved by the Ethics Committee of Zhejiang University. The enrolled patients signed a written informed consent form. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The original contributions presented in the study are included in the article/Supplementary Material. Detailed clinical baseline data is available at BIG Submission (BIG SUB, , OMIX ID:OMIX004322). * CAD : coronary artery disease TMAO : trimethylamine-N-oxide CAMP : cationic antimicrobial peptide BNP : brain natriuretic peptide cTNI : cardiac troponin I CK : creatine kinase CRP : C-reactive protein SCFA : short chain fatty acids PBMCs : peripheral blood mononuclear cells DGE : differential gene expression FDR : false discovery rate GSEA : gene set enrichment analysis ORA : over representative analysis KEGG : the Kyoto Encyclopedia of Genes and Genomes AUC : area under the ROC curve.