Alterations in the Salivary Microbiome and Metabolism in Patients With Carotid Atherosclerosis from Rural Northeast China

Background Periodontitis and atherosclerosis are both chronic inflammatory diseases with a high prevalence. Increasing evidence supports the independent association between severe periodontitis and atherosclerotic cardiovascular disease, in which oral microorganisms may play an important role. We aimed to evaluate the characteristic changes of salivary microbiome and metabolome in patients with carotid atherosclerosis (CAS) and periodontitis. Methods and Results The subjects were obtained from a cross‐sectional study that included 1933 participants aged 40 years or older from rural northeast China. The study enrolled 48 subjects with CAS and 48 controls without CAS matched by sex, age, body mass index, and prevalence of hypertension, diabetes, and dyslipidemia. We performed full‐length 16S rDNA gene sequencing and untargeted metabolomics of saliva samples from 96 subjects. We found that CAS was closely associated with an increased abundance of Streptococcus, Lactobacillus, and Cutibacterium. Furthermore, patients with CAS had higher prevalence of severe periodontitis than the control group. Notably, periodontal pathogens such as Tannerella and Anaeroglobus were not only associated with periodontitis but also enriched in patients with CAS, whereas periodontal health‐associated Neisseria was more abundant in those without CAS. We also identified 2 lipid metabolism pathways, including glycerophospholipid and sphingolipid metabolism, as associated with CAS. The levels of trimethylamine N‐oxide and inflammatory mediator leukotriene D4 were significantly higher in patients with CAS, whereas the levels of carnosine were significantly lower, than those in controls. Additionally, serum levels of inflammatory marker high‐sensitivity C‐reactive protein were significantly increased in CAS and positively correlated with the abundance of Anaeroglobus and leukotriene D4 in saliva. Conclusions Our study suggests that characteristic changes in salivary microbiota and metabolites are closely related to CAS, and periodontitis and associated microorganisms may be involved in the initiation and progression of CAS.