Characteristics Of Gut Microbiome In Patients With Coronary Artery Ectasia(CAE)

OBJECTIVE:Coronary artery ectasia(CAE)is defined as 1.5 times wider in diameter of abnormal coronary artery than normal coronary artery.It has been listed as rare disease by China and many countries.Pathogeneses are still unknown,making prevention,screening,treatment and patient management challengingl Currently,pathogeneses consist of chronic inflammation,extracellular matrix degradation,metabolites production and autoimmune process.Due to the recent exploration of gut microbiome,researchers have found tightly associations between gut microbiome and those pathogeneses,however,there is no research studying CAE patients’ gut microbiome characteristics for now.Thus,knowing the components and functions of CAE patients’ gut microbiome may be a core step of understanding its pathogeneses.The focus of this study will be understanding the structure and function of CAE patients’ gut microbiome,providing new insights into research and management of this disease.METHODS:In this study,the study plan is designed as a case-control matching study,in which the sex,age and status of coronary atherosclerosis disease are matched.In the study,there are 54 patients recruited,with 18 CAE patients and 36 Non-CAE participants.The information of demographic,clinical history,food history and stool history,also physical examination,blood samples and faecal samples are collected in a standardized way.The blood is used for lab test,the faecal is used in a 16S rDNA sequencing.Based on collected information,several platforms,databases and software are used to perform bioinformatics and statistical analysis.RESULTS:With the use of a matched process,age,sex and past medical history show no significant differences.In the diversity analysis,there are no significant differences found in a-diversity,while β-diversity is observed with significant differences between groups.Further analysis of differential floras shows Actinobacteria phylum is enriching in CAE group.At the genus level,8 genera,including Collinsella,Blautia,Streptococcus and Actinomyces etc.,have higher relative abundance in CAE group,while 5 genera,including 3 genera in Ruminococcaceae,Flavonifractor and Shigella,are in lower relative abundance in CAE group.Collinsella has been proved to be in positive association with chronic inflammation and cell adhesion molecules,which may play a role in pathogeneses of CAE.Also,the high relative abundance of Blautia,Streptococcus and Actinomyces indicates a potential role of autoimmune process in CAE,as they have been found to have an high relative abundance in autoimmune diseases patients.Meanwhile,in prediction of functions,19 pathways show differences between two groups at KEGG level 3,containing mainly glycan metabolism and amino acid metabolism.In glycan metabolism,peptidoglycan synthesis is increased,glycosaminoglycan degradation is decreased,leading to an accumulation of the products,while lipopolysaccharide synthesis is decreased.In amino acid metabolism,for aromatic amino acid,phenylalanine metabolism shows a decrease,yet tyrosine metabolism shows an increase.Branched-chain amino acids(BCAA)are observed with decreased degradation.The accumulation of peptidoglycan,glycosaminoglycan and BCAA has been proved to enhancing CAE-related pathways.In correlation analysis,only grouping and use of statin show a weak correlation with differential floras.Then,a within-group analysis of diffuse or local ectasia reveals no significance.Lastly,potential confounding factors are tested and reported,in which oral use of statin showed a significant effect.CONCLUSION:There are significant differences between CAE and Non-CAE groups in β-diversity,differential floras and prediction of functions,which could be a contribution to pathogeneses,and also call for further study of microbiome’s role in CAE.