Gut Microbiota as Potential Biomarker and/or Therapeutic Target to Improve the Management of Cancer: Focus on Colibactin-Producing Escherichia coli in Colorectal Cancer

Abstract

The gut microbiota is crucial for physiological development and immunological homeostasis. Alterations of this microbial community called dysbiosis, have been associated with cancers such colorectal cancers (CRC). The pro-carcinogenic potential of this dysbiotic microbiota has been demonstrated in the colon. Recently the role of the microbiota in the efficacy of anti-tumor therapeutic strategies has been described in digestive cancers and in other cancers (e.g., melanoma and sarcoma). Different bacterial species seem to be implicated in these mechanisms: F. nucleatum, B. fragilis, and colibactin-associated E. coli (CoPEC). CoPEC bacteria are prevalent in the colonic mucosa of patients with CRC and they promote colorectal carcinogenesis in susceptible mouse models of CRC. In this review, we report preclinical and clinical data that suggest that CoPEC could be a new factor predictive of poor outcomes that could be used to improve cancer management. Moreover, we describe the possibility of using these bacteria as new therapeutic targets.

Molecular Mechanisms of Cancer Drug Resistance: Emerging Biomarkers and Promising Targets to Overcome Tumor Progression

“…In particular, CoPEC bacteria is the prevailing species in the colonic mucosa of CRP patients and trigger colorectal tumorigenesis by causing DNA double-strand breaks, increased ROS production, as well as chromosomal instability. These observations support the notion that CoPEC might be considered both a factor predictive of poor outcomes and a possible effective therapeutic target in CRC [ 35 ].…”

Relationship between gut microbiota and lung function decline in patients with chronic obstructive pulmonary disease: a 1-year follow-up study

“…The microbiota could be used as potential markers for the progression of HBV-related acute-on-chronic liver failure [ 46 ] and the management of cancer [ 47 ]. Previous studies indicated that gut microbiota regulated lung inflammation [ 48 ] and was associated with respiratory diseases [ 49 ].…”

The Nutrition-Microbiota-Physical Activity Triad: An Inspiring New Concept for Health and Sports Performance

“…Dysbiosis can promote cancer onset and/or progression through different mechanisms: (i) The presence of specific microorganisms or of intestinal dysbiosis has been associated with some tumors. First, the pathogen can cause DNA lesions, for example, through the production of genotoxins, as reported for Helicobacter pylori , a bacterium that increases the risk of gastric cancer [ 30 , 31 ], and colibactin-producing E. coli , a bacterium that increases the risk of colorectal cancer [ 32 , 33 , 34 ]. Second, the microbiota imbalance favors some species ( Fusobacterium ) that can abnormally stimulate oncogenic pathways, such as the beta-catenin signaling pathway [ 35 ]; (ii) The close interaction between microbiota and local immunity [ 36 , 37 ].…”