Alterations in oral metabolomics and microbiomics across CRC progression and identification of potential metabolic biomarkers

Background Oral microbiota can enter the gut via the oral-gut axis, leading to alterations in intestinal microbiota and their metabolites, which promote colorectal cancer (CRC). Relevant studies have shown that improving the detection rate of colorectal adenomas and performing timely removal can significantly reduce the incidence and mortality of CRC. Therefore, this study aims to elucidate changes in oral microbiota and their associated metabolites during the progression of CRC, clarify the relationship between these alterations and the onset and development of CRC, and identify potential metabolic biomarkers. Results We performed LC–MS/MS metabolomic profiling and 16S rRNA gene sequencing analyses on oral samples from 23 patients with CRC, 19 patients with colorectal adenomas (CRA), and 22 normal controls (NC). Metabolomic analysis revealed significant differences in metabolites among the NC, CRA, and CRC groups. Notably, Tauro-b-muricholic acid exhibited a progressive increasing trend from NC to CRA and then to CRC. Metabolites associated with CRC were significantly enriched in the Glycerophospholipid metabolism pathway, as well as in pathways related to infections and autoimmune diseases such as systemic lupus erythematosus and leishmaniasis. ROC curve analyses of metabolites between CRC vs. NC and CRC vs. CRA yielded AUC values of 0.95 and 0.91, respectively, suggesting its potential value in exploratory studies of noninvasive CRC diagnosis. Regarding microbiome analysis, both α-diversity and β-diversity analyses indicated significant differences in microbial community composition among the NC, CRA, and CRC groups. LEfSe analysis further identified that, compared with the NC group, g__ Veillonella , g__ Actinomyces , g__ Leptotrichia , and g__ Stomatobaculum were significantly enriched in CRC group. Compared with the CRA group, g__ Selenomonas and g__ Megasphaera were significantly enriched in CRC group. Correlation analyses between microbiota and metabolites demonstrated that the potential metabolite biomarkers enriched in CRC were significantly positively correlated with the aforementioned differential taxa. Conclusion This study, through integrated metabolomic and microbiome analyses, demonstrated that both oral metabolites and oral microbiota are altered during the development of colorectal cancer. It highlighted potential early-driver metabolites across stages of colorectal carcinogenesis and identified novel candidate biomarkers from the oral metabolome for early, non-invasive risk screening of colorectal cancer.