Oral microbial alterations by smoking and metabolic factors in esophageal squamous cell carcinoma.

Background: It is important to understand how clinical factors affect microbial profiles, but few studies have evaluated these associations in patients with esophageal squamous cell carcinoma (ESCC). This study aimed to analyze differences in the oral microbiome between patients with ESCC and healthy controls, with subgroup analyses stratified by clinical and metabolic factors. Methods: From December 2021 to May 2023, oral swab samples and clinical data were collected from participants at five tertiary medical centers. Clinical data included age, sex, body mass index (BMI), smoking history, metabolic profiles such as cholesterol, triglycerides (TG), low-density lipoprotein (LDL), and high-density lipoprotein, and endoscopic findings. Sequencing and taxa abundance analyses were performed to compare oral microbiota between patients with ESCC and controls. Subgroup analyses were conducted to explore the impact of clinical factors on microbial community composition and diversity. Results: No significant differences in α- or β-diversity were observed between ESCC patients (n=21) and controls (n=20). However, subgroup analyses revealed distinct microbial patterns. Haemophilus parainfluenzae was less abundant in younger and low-LDL ESCC patients compared to controls, while Veillonella dispar was more abundant in older and high-LDL ESCC patients. Streptococcus infantis was less abundant in ESCC patients under 65 years compared to controls, and in smoking patients compared to non-smoking patients. Conclusions: The oral microorganisms H. parainfluenzae, V. dispar, and S. infantis may serve as potential biomarkers influenced by metabolic factors in ESCC.