Tumor-associated microbiota in colorectal cancer with vascular tumor-thrombus and neural invasion and association with clinical prognosis

Abstract Background Neural invasion (NI) and vascular tumor thrombus (VT) are associated with poor prognosis in patients with colorectal cancer (CRC). But little is known about the changes of gut microbiota in CRC tissues with invasion. In this study, we applied 16S rRNA amplicon sequencing to tumor tissues and adjacent normal tissues in patients with CRC to determine the microbial differences. Results A discovery cohort (n = 88), including 30 patients with NI, 23 with VT, and 35 with double-negative CRC tissue, was utilized. We analyzed the relationship between the differential bacterial taxa and survival prognosis in an analysis cohort (n = 82) and explored the association of the special microorganisms with the clinical characteristics in an expanded cohort (n = 286) as well as their association with the survival prognosis in the overall cohort (n = 329). In the discovery cohort, the diversity, composition, and metabolic pathways of the gut microbiome distinctly differed between the tumor and non-tumor tissues in the NI and VT groups. Compared with the species richness of the microbiota communities of the noninvasive tumor tissues of the double-negative group, that of the tumor tissues of the NI and VT groups decreased. At the genus level, the four dominant bacteria in the NI and VT groups were Cupriavidus , Acinetobacter , Sphingobium , and Thermus . A high abundance of Cupriavidus was found to be related to a short survival time of NI CRC in the Kaplan–Meier analysis. Simultaneously, Herbaspirillum was a potential microbial biomarker predicting the prognosis of patients with CRC with NI or VT. Moreover, an abundance of Cupriavidus was associated with the NI status, pN stage, and clinical stage, while that of Herbaspirillum was related to the tumor diameter, NI status, pN stage, distant metastasis, and clinical stage. In the overall cohort, a high abundance of Cupriavidus and Herbaspirillum also indicated a poor prognosis. Conclusion This study is the first to comprehensively elaborate the differences in the gut microbiota of patients with CRC with different invasion statuses and to prove the relationship between some gut microbiota and clinical patient characteristics.