Periodontitis Exacerbates Colorectal Cancer by Altering Gut Microbiota–Derived Metabolomics in Mice

ABSTRACT Aim The correlation between periodontitis and colorectal cancer (CRC) has drawn widespread attention. However, how periodontitis affects CRC progression remains unclear. Methods C57BL/6 mice were used to establish experimental periodontitis and CRC model. Histological alterations of periodontium and colon were observed by hematoxylin and eosin staining. Micro‐computed tomography (micro‐CT) was applied to evaluate alveolar bone loss (ABL). Tumor growth was detected by immunofluorescence. Gut bacteria were analyzed using 16S rRNA sequencing. Gas chromatography–mass spectrometry (GC–MS) was performed to observe the alterations of gut microbial metabolites. The detection of associated pathways was carried out using quantitative real‐time PCR (qRT‐PCR). Results Experimental periodontitis significantly induced increases in tumor number in mice with CRC. Double immunofluorescence for Ki67 and β‐catenin, as well as Cyclin D1 and β‐catenin, indicated that experimental periodontitis observably promoted tumor growth. 16S rRNA sequencing and untargeted metabolomics analysis displayed that experimental periodontitis altered gut microbial community and metabolite profiles in CRC mice. Notably, we found that experimental periodontitis dramatically increased the level of three oncometabolites (serotonin, adenosine, and spermine) in mice with CRC. Conclusion Alterations of gut microbial community and metabolites might be relevant in experimental periodontitis deteriorating CRC.