The virus integrations in gut microbes associated with dysbiosis of microbial community in tumorigenesis of colorectal carcinoma

Abstract

Patients with colorectal cancer (CRC) have a different gut microbial and viral communities from healthy individuals. But little is known about the ways and functions of interaction of virus-bacteria, let alone its correlation with the aetiology of CRC. In this study we aimed to identify the association between the genetic integration of virusbacteria and the expansion of some microbial population during tumorigenesis of human colorectum. Using a gut metagenomics sequencing data of healthy controls, advanced adenoma and carcinoma patients, to our knowledge, we demonstrate for the first time that the viral genetic integrations in gut microbes tend to occur in CRC patients and are potentially associated with the carcinogenesis. We found that almost all of the genetic integrations were happened between bacteriophages and bacteria, which could be influenced by the abundance of the phage communities. Importantly, the integrations of phage-carried positive effective genes offered selective advantages to the commensal and potential pathogenic bacteria, as a result, potentially led to a microbial dysbiosis along with the increasing bacterial diversity in carcinoma patients.Consequently, our work opens a new way to understand the carcinogenicity in complex intestinal ecosystems.Colorectal cancer (CRC) is among the top three most common cause of cancer mortality in the world. Most of the CRC cases are referred to as the order of adenoma-carcinoma that could progress into malignant forms [1][2][3]. The accumulation of genetic mutations for many years is the most important reason for the development of CRC, which is affected by many factors such as lifestyle and environment including the gut microbiota [4-6]. The human gut microbiome is composed of a large number of bacterial cells, along with a minority of virus, archaeal and eukaryotic cells, together forming a very complex intestinal microbial ecosystem [7]. The virus is primarily made up of bacteriophages and also includes rarer eukaryotic viruses and endogenous retroviruses [8-10].Accumulating data have demonstrated that the composition of gut microbiota in CRC patients are distinct from healthy individuals [11,12]. On the one hand, emerging evidences have indicated that several bacteria, such as Bacteroides fragilis [13], Fusobacterium nucleatum (F. nucleatum) [6,14] and a strain of Escherichia coli [4], are more abundant in the gut of CRC patients or CRC tissues and have been found to be associated with CRC development by promoting colorectal carcinogenesis. These microbes can accelerate carcinoma development through secretion of oncogenic virulence factors [15], generation of carcinogenic microbial metabolites [16,17] or recruitment of immune cells [18,19] and so on. On the other hand, an increasing number of studies suggest that the human intestinal microbiota contributes to CRC via the influence of the whole microbial community, especially the dysbiosis of the bacterial population that is a result of symbiotic, commensal, and pathobiont interactions among microorgan...