Human Salivary Microbiome as the Novel Non-invasive Biomarker in Early-onset Colorectal Cancer Screening: A Prospective Study

Background: The incidence of Early-onset colorectal cancer (EOCRC) has been increasing in recent years, and oral microbiota alterations are linked with the carcinogenesis of CRC. However, it is not known if salivary microbiome could help the detection of EOCRC. Here, we aimed to investigate whether salivary microbiome has the underlying value in EOCRC screening as the novel non-invasive biomarker.Methods: We collected the saliva sample from 65 EOCRC patients and 63 control individuals. The saliva microbiota was assessed by using high-throughput 16S ribosomal RNA gene V3-V4 region sequencing. We profiled the saliva microbiota and developed EOCRC screening models by using machine learning (ML) algorithms.Results: Alpha diversity was comparable between the salivary microbiome of EOCRC patients and control individuals, while beta diversity exhibited statistical difference between two groups. Differential analysis of the saliva microbial communities at the genus level revealed Prevotella, Actinomyces, and Corynebacterium were more abundant in EOCRC patients, whereas Fusobacterium, Haemophilus, norank_o__Absconditabacteriales_SR1, norank_c__Gracilibacteria, Peptococcus, Eikenella, and Eubacterium_yurii_group were less abundant in EOCRC patients. Furthermore, in developing the EOCRC screening model based on the salivary microbiome, the neural network model demonstrated the best performance, achieving an AUC of 0.780 and a recall of 0.929, effectively distinguishing EOCRC patients from control individuals.Conclusions: This study firstly highlights the potential dysbiosis of salivary microbiota in EOCRC patients and suggests that salivary microbiome-based biomarkers may serve as a novel non-invasive tool for EOCRC screening.