Gut Microbiota, Inflammation, and Colorectal Cancer

Abstract

Colorectal cancer is the second-leading cause of cancer-related deaths in the United States and fourth-leading cause of cancer-related deaths worldwide. While cancer is largely considered to be a disease of genetic and environmental factors, increasing evidence has demonstrated a role for the microbiota (the microorganisms associated with the human body) in shaping inflammatory environments and promoting tumor growth and spread. Herein, we discuss both human data from meta’omics analyses and data from mechanistic studies in cell culture and animal models that support specific bacterial agents as potentiators of tumorigenesis—including Fusobacterium nucleatum, enterotoxigenic Bacteroides fragilis, and colibactin-producing Escherichia coli. Further, we consider how microbes can be used in diagnosing colorectal cancer and manipulating the tumor environment to encourage better patient outcomes in response to immunotherapy treatments.

Relationship of the mucosal microbiota to gastrointestinal inflammation and small cell intestinal lymphoma in cats

“…Fusobacterium nucleatum numbers are significantly correlated with tumor size, and shortened survival times in a population of human Japanese patients with later stage CRC compared to earlier stages 53. These findings, as well as additional observations in rodent models and humans with CRC suggest that chronic inflammatory disease of the GI tract is a potential risk factor for the development of additional channels for amplified inflammatory processes, aneuploidy, high‐grade dysplasia, metaplasia and loss of cellular proliferative checkpoints, all of which are processes that can be appreciated in malignancy 13, 19, 54, 58, 59. The increased numbers of mucosal Fusobacterium spp.…”

“…Although incompletely understood, GI inflammation‐mediated progression to cancer development might involve bacterial toxin production, release of alarmins, gut biofilm modification, dysregulation of gut barrier function, suppression of anti‐inflammatory mediators and transition through an element of high grade dysplasia to cell damage and aneuploidy 13, 19, 35, 40, 60, 61, 62…”

“…numbers and both CD11b + and NF‐κB expressing cells. Furthermore, CD11b + myeloid cells might contribute to development of a tumor microenvironment,19, 63 and Fusobacterium spp. might induce toll like receptors (TLR), to stimulate NF‐κB through the TLR4/MYD88 pathway 54.…”

“…, Enterobacteriaceae , Fusobacterium spp.) might drive a tumor‐permissive milieu characterized by mucosal infiltration with specialized effector cells, including CD11b + myeloid cell derived macrophages, as observed in humans, and rodent models 9, 19, 21, 22…”

“…dysbiosis) is associated with development of benign mixed mucosal inflammation (lymphoplasmacytic enteritis with IBD) and GI lymphoid malignancy 9, 10, 15, 16, 17, 18. Microbial imbalances have also been implicated in the pathogenesis of approximately 20% of all human malignancies, including GI neoplasia such as colorectal adenocarcinomas and gastric carcinomas 19, 20, 21. Both chronic, high‐grade inflammation of disorders such as feline IBD, and lower grade smoldering inflammation attributable to pro‐inflammatory bacteria (e.g.…”