Characteristics of the Oral and Gastric Microbiome in Patients with Early-stage Intramucosal Esophageal Squamous Cell Carcinoma

Abstract Background Oral microbiome dysbacteriosis has been reported to be associated with the pathogenesis of advanced esophageal cancer, especially the adenocarcinoma type. However, few studies investigated the potential role of oral and gastric microbiota in early-stage intramucosal esophageal squamous carcinoma (EIESC). Method A total of 104 samples, including 52 paired salivae and biopsies of the gastric antrum, were collected from 31 patients with EIEEC and 21 healthy controls. The oral and gastric microbiota compositions were compared at different taxonomics, using the amplicon 16s-rRNA sequence. The correlation between oral microbiota and clinicopathological factors was assessed. Co-occurrence networks were established in both oral and gastric microbial communities. Random forest models were used to determine significant microbial biomarkers for differentiating EIESC and control groups. Results A total of 292 oral genera and 223 species (excluding unidentified species) were identified in both EIESC and healthy controls. Six oral genera were remarkably enriched in EIESC groups, including the genera Porphyromonas, Shigella, Subdoligranulum, Leptotrichia, Paludibacter, and Odoribacter. LEfSe analysis identified the genera Porphyromonas and Leptotrichia with LDA scores > 3. In the random forest model, Porphyromonas endodontalis ranked the top microbial biomarker to differentiate EIESC from controls. The elimination rate of Porphyromonas endodontalis from the oral cavity to the stomach was also dramatically decreased in the EIESC group than controls. In the microbial co-occurrence network, Porphyromonas endodontalis was positively correlated with Prevotella tannerae and Prevotella intermedia and was negatively correlated with Veillonella dispar. Conclusion Our study provides evidence that the dysbacteriosis of both the oral and gastric microbiome was associated with early-stage of esophageal squamous cell carcinoma. Larger scale studies and experimental animal models are urgently needed to confirm the possible role of microbial dysbacteriosis in the pathogenesis of esophageal cancer, especially at an early stage. (Chinese Clinical Trial Registry Center, ChiCTR2200063464, Registered 07 September 2022, https://www.chictr.org.cn/showproj.html?proj=178563)