Infectious Carcinogens Derived from Intestinal Microflora: Mechanisms of Microbial Transitions from Eubionts to...

A diverse community of microorganisms inhabits the gastrointestinal tract in a physiological state. While a symbiotic relationship exists between commensal bacteria and the healthy host, an imbalanced microbial population (dysbiosis) is associated with the development of colitis-associated colorectal cancers. The decline of beneficial microbes (eubionts) and the expansion of commensal-derived opportunistic pathogens (pathobionts) are widely recognized as key factors in the microbial etiology of various diseases. In particular, certain bacteria with emerging virulence elements are present in the gut microbiome and have been implicated as contributors to the development of colon cancer, such as Escherichia coli , Bacteroides fragilis , and Fusobacterium nucleatum . Bacterial virulent factors, including lipopolysaccharide, fimbriae and adhesins, and toxins, promote oncogenesis through direct or indirect mechanisms. These microbial products modify host cellular functions, resulting in DNA damage, increased epithelial proliferation, and intensified inflammation, all of which ultimately contribute to tumor formation. Although the existence of pathobionts is generally accepted nowadays, an open question remains regarding why bacteria shift from harmless commensals to disease-causing pathobionts. Accumulating evidence suggests that host epithelial functions influence the composition of the intestinal microbiota by regulating oxygen availability in the lumen, providing antimicrobial defense, activating innate immune responses, synthesizing mucin glycoproteins, and establishing a physical barrier through the organization of microvilli. This review examines the various aspects of mucosal drivers that shape microbiota and provides evidence that intraepithelial stress plays a significant role in configuring colitogenic and tumorigenic microflora. Understanding the mechanisms by which microbes transition from eubionts to pathobionts that promote cancer progression is crucial for developing bacterial precision medicine. Identifying the roles of intestinal pathobionts and the critical time point for host-microbe interactions in tumorigenesis could lead to the development of new strategies for prevention and therapy.