Oral Microbiome Dysbiosis Is Associated With Precancerous Lesions and Disorders of Upper Gastrointestinal Tract: A Population-Based Study

口腔微生物群失调与上消化道癌前病变和疾病相关:一项基于人群的研究

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Abstract

INTRODUCTION: Oral microbiota may contribute to the development of upper gastrointestinal (UGI) disorders. In this study, we evaluated the association between microbiota of saliva, subgingival, and buccal mucosa and UGI disorders, particularly precancerous lesions. We also aimed to identify which oral site have the greatest potential as biomarkers for the development of UGI cancers. METHODS: In this population-based study, 388 adults underwent upper endoscopy with biopsies for histopathological analysis. UGI symptoms were assessed using a validated questionnaire, and 16S rRNA gene sequencing characterized the microbiota in 380 saliva, 200 subgingival, and 267 buccal mucosa samples collected during endoscopy. RESULTS: Dysbiosis of the salivary microbiota was observed in subjects with gastroesophageal reflux symptoms (GERSs) alone, as well as in those with combined conditions such as GERS and esophagitis, or esophagitis and Barrett's esophagus. Significant microbial alterations were also found in individuals with several stomach disorders including Helicobacter pylori infection, chemical reactive gastritis, atrophic gastritis, and intestinal metaplasia. However, microbiota dissimilarity in subgingival and buccal mucosa samples was primarily associated with Barrett's esophagus or gastric atrophy. Among identified genera in saliva, the association between Prevotella and Fusabacterium and atrophic gastritis and intestinal metaplasia was notable. In subgingival samples, the link of Fretibacterium with Barrett's esophagus and Fusabacterium with gastric atrophy and intestinal metaplasia has also been found to be important. DISCUSSION: Dysbiosis of saliva microbiota is linked to a broad spectrum of UGI disorders. However, microbiota dysbiosis in subgingival and buccal mucosa sites is specifically associated with the premalignant conditions such as Barrett's esophagus and gastric atrophy. Among oral sites, the subgingival microbiota shows more potential as a infectious biomarker for UGI cancers.

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