The role of intestinal bacteria in the development and progression of gastrointestinal tract neoplasms

Abstract

More than 100 trillion microorganisms inhabit the human intestinal tract and play important roles in health conditions and diseases, including cancer. Accumulating evidence demonstrates that specific bacteria and bacterial dysbiosis in the gastrointestinal tract can potentiate the development and progression of gastrointestinal tract neoplasms by damaging DNA, activating oncogenic signaling pathways, producing tumor-promoting metabolites such as secondary bile acids, and suppressing antitumor immunity. Other bacterial species have been shown to produce short-chain fatty acids such as butyrate, which can suppress inflammation and carcinogenesis in the gastrointestinal tract. Consistent with these lines of evidence, clinical studies using metagenomic analyses have shown associations of specific bacteria and bacterial dysbiosis with gastrointestinal tract cancers, including esophageal, gastric, and colorectal cancers. Emerging data demonstrate that intestinal bacteria can modulate the efficacy of cancer chemotherapies and novel targeted immunotherapies such as anti-CTLA4 and anti-CD274 therapies, the process of absorption, and the occurrence of complications after gastrointestinal surgery. A better understanding of the mechanisms by which the gut microbiota influence tumor development and progression in the intestine would provide opportunities to develop new prevention and treatment strategies for patients with gastrointestinal tract cancers by targeting the intestinal microflora.

Gastrointestinal and Hepatobiliary Disease in Cystic Fibrosis

“…128 Meanwhile, a growing body of literature indicates that intestinal microbial dysbiosis may play a role in tumorigenesis, by damaging DNA, activating oncogenic signaling pathways, producing mutagenic metabolites, suppressing antitumor immunity, and promoting inflammation, which may in turn induce the expression of microorganisms with genotoxic capabilities. 129,130 In support of this, bowel cancer risk is particularly high among patients classified as having severe genotype or a history of DIOS. 123 Further, patients with CF are at significantly increased risk for CRC after lung transplantation relative to nontransplanted CF patients and non-CF recipients, suggesting that some of these processes may be exacerbated by immunosuppressants.…”

Endoscopic gastric mucosal atrophy as a predictor of colorectal polyps: a large scale case-control study

“…(12) Multiple publications have indicated the relationship between intestinal microbiota and colorectal carcinogenesis. (43)(44)(45) Gavage of fecal samples from patients with colorectal cancer have shown the occurrence of colorectal polyps with proinflammatory gene expressions and oncogenic factors in germ-free and conventional mice. (46) These outcomes support the hypothesis that intestinal dysbiosis derived from the hypochlorhydria in the stomach can cause colorectal neoplasms.…”

Pathogenic Activity of Methicillin-Resistant Staphylococcus aureus Strains Isolated from Colorectal Cancer Patients

“…They play an important role in health status and diseases, including cancer. Specific bacteria and gastrointestinal dysbiosis can potentiate the development and progression of gastrointestinal neoplasms by destroying DNA, activating oncogenic signaling pathways, producing metabolites that promote the development of tumors and suppressing antitumor immunity [8].…”