Abstract
The incidence of sporadic young-onset colorectal cancer (yCRC) is increasing. A significant knowledge gap exists in the gut microbiota and its diagnostic value for yCRC patients. Through 16S rRNA gene sequencing, 728 samples are collected to identify microbial markers, and an independent cohort of 310 samples is used to validate the results. Furthermore, species-level and functional analysis are performed by metagenome sequencing using 200 samples. Gut microbial diversity is increased in yCRC. Flavonifractor plautii is an important bacterial species in yCRC, while genus Streptococcus contains the key phylotype in the old-onset colorectal cancer. Functional analysis reveals that yCRC has unique characteristics of bacterial metabolism characterized by the dominance of DNA binding and RNA-dependent DNA biosynthetic process. The random forest classifier model achieves a powerful classification potential. This study highlights the potential of the gut microbiota biomarkers as a promising non-invasive tool for the accurate detection and distinction of individuals with yCRC.
Highlights
The incidence of sporadic young-onset colorectal cancer is increasing
1038 eligible cases including 185 young-onset colorectal cancer (yCRC), 379 oldonset CRC (oCRC), 217 age-matched healthy controls for the yCRC and 257 age-matched healthy controls for the oCRC were included in this study according to the strict recruitment process (Fig. 1)
The microbial markers and classifier were identified by random forest model between Colorectal cancer (CRC) and agematched control (163 oCRC vs. 142 oControl; 100 yCRC vs. 104 yControl)
Summary
The incidence of sporadic young-onset colorectal cancer (yCRC) is increasing. A significant knowledge gap exists in the gut microbiota and its diagnostic value for yCRC patients. Young-onset CRC (yCRC) patients often present with more advanced disease and adverse pathological features compared to their older counterparts[7]. This may have a negative impact on their survival outcome[8,9]. The potential of the gut microbiota to affect health is relevant for older or younger individuals because the microbiota may modulate aging-related changes in innate immunity, inflammation, and cognitive function[12,13]. Both cell culturedependent and -independent studies have shown that the gut microbiota of the elderly is different from that of the young[14,15]. We hypothesize that the yCRC and oCRC may have different gut microbial bases, which may shed light on the pathogenesis of CRC at different ages, and may serve as a promising non-invasive biomarker for sporadic yCRC
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