Analyses of Potential Driver and Passenger Bacteria in Human Colorectal Cancer

Cancer Manag Res. 2020 Nov 12:12:11553-11561. doi: 10.2147/CMAR.S275316. eCollection 2020.

Abstract

Introduction: Besides genetic and epigenetic alterations that lead to carcinogenesis and development of colorectal cancer (CRC), intestinal microbiomes are recently recognized to play a critical role in CRC progression. The abundant species associated with human CRC have been proposed for their roles in promoting tumorigenesis. However, a recent "driver-passenger" model suggests that these CRC-associated species with high relative abundances may be passenger bacteria that take advantage of the tumor environment instead of initiating CRC, whereas the driver species that initiate CRC have been replaced by passenger bacteria due to the alteration of the intestinal niche.

Methods: Here, to reveal potential driver and passenger bacteria during CRC progression, we compare the gut mucosal microbiomes of 75 triplet-paired CRC samples collected from on-tumor site, adjacent-tumor site, and off-tumor site, and 26 healthy controls.

Results: Our analyses revealed potential driver bacteria in four genera and two families, and potential passenger bacteria in 14 genera or families. Bacillus, Bradyrhizobium, Methylobacterium, Streptomyces, Intrasporangiaceae and Sinobacteraceae were predicted to be potential driver bacteria. Moreover, 14 potential passenger bacteria were identified and divided into five groups. Group I passenger bacteria contain Fusobacterium, Campylobacter, Streptococcus, Schwartzia, and Parvimonas. Group II passenger bacteria contain Dethiosulfatibacter, Selenomonas, Peptostreptococus, Leptotrichia. Group III passenger bacteria contain Granulicatella. Group IV passenger bacteria contain Shewanella, Mogibacterium, and Eikenella. Group V passenger bacteria contain Anaerococus. Co-occurrence network analysis reveals a low correlation relationship between driver and passenger bacteria in CRC patients compared with healthy controls.

Discussion: These driver and passenger species may serve as bio-marker species for screening cohorts with high risk to initiate CRC or patients with CRC, respectively. Further functional studies will help understand the roles of driver and passenger bacteria in CRC initiation and development.

Keywords: colorectal cancer; driver-passenger model; microbiota.

Grants and funding

This research was funded by the Natural Science Foundation of China Grant number 81972826, and the Fundamental Research Funds for the Central Universities, Nankai University Grant number 63191440, and Key R&D Projects in the Tianjin Science and Technology Pillar Program Grant number 19YFZCSY00420, and National key R&D Program of China Grant number 2017YFC1700604, and National key R&D Program of China Grant number 2017YFC1700606, and Tianjin 131 Innovative Talent Training Project in 2018, and the Research Foundation of Tianjin Union Medical Center number 2018YJ023.