Analyses of Potential Driver and Passenger Bacteria in Human Colorectal Cancer

Abstract

Yijia Wang,1,* Chunze Zhang,2,* Shaobin Hou,3 Xiaojing Wu,1 Jun Liu,4 Xuehua Wan5 1Laboratory of Oncologic Molecular Medicine, Tianjin Union Medical Center, Nankai University, Tianjin, People’s Republic of China; 2Department of Colorectal Surgery, Tianjin Union Medical Center, Nankai University, Tianjin, People’s Republic of China; 3Advanced Studies in Genomics, Proteomics, and Bioinformatics, University of Hawaii at Manoa, Honolulu, HI, USA; 4Department of Radiology, Tianjin Union Medical Center, Nankai University, Tianjin, People’s Republic of China; 5TEDA Institute of Biological Sciences and Biotechnology, Nankai University, TEDA, Tianjin, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jun LiuTianjin Union Medical Center, No. 190, Jieyuan Road, Hongqiao District, Tianjin City, People’s Republic of ChinaEmail [email protected] WanNankai University, No. 94, Weijin Road, Nankai District, Tianjin City, People’s Republic of ChinaEmail [email protected]: 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take advantage of the tumor environment instead of initiating CRC, whereas the driver species that initiate CRC have been replaced by passenger bacteria due to the alteration of the intestinal niche.Methods: Here, to reveal potential driver and passenger bacteria during CRC progression, we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

Keywords

• colorectal cancer
• ‘driver-passenger’ model
• microbiota