Role of gut microbiota-immunity axis in patients undergoing surgery for colorectal cancer: Focus on short and long-term outcomes

Abstract

Human body is colonized by a huge amount of microorganisms mostly located in the gastrointestinal tract. These dynamic communities, the environment and their metabolites constitute the microbiota. Growing data suggests a causal role of a dysbiotic microbiota in several pathologies, such as metabolic and neurological disorders, immunity dysregulations and cancer, especially the well-studied colorectal cancer development. However, many were preclinical studies and a complete knowledge of the pathogenetic mechanisms in humans is still absent. The gut microbiota can exert direct or indirect effects in different phases of colorectal cancer genesis. For example, Fusobacterium nucleatum promotes cancer through cellular proliferation and some strains of Escherichia coli and Bacteroides fragilis produce genotoxins. However, dysbiosis may also cause a proinflammatory state and the stimulation of a Th17 response with IL-17 and IL-22 secretion that have a pro-oncogenic activity, as demonstrated for Fusobacterium nucleatum. Microbiota has a crucial role in several stages of postoperative course; dysbiosis in fact seems related with surgical site infections and Enterococcus faecalis (and other collagenase-producers microbes) are suggested as a cause of anastomotic leak. Consequently, unbalanced presence of some species, together with altered immune response may also have a prognostic role. Microbiota has also a substantial role in effectiveness of chemotherapy, chemoresistance and in the related side effects. In other words, a complete knowledge of the fine pathological mechanisms of gut microbiota may provide a wide range of new diagnostic tools other than therapeutic targets in the light of tailored medicine.

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

“…In particular, anastomotic leaks (AL) constitute the most life-threatening postoperative complications following colorectal procedures (ranging from 2 to 19%) despite a consistent improvement of surgical techniques and perioperative care [ 90 ]. The potential role of gut microbiota on the pathogenesis of AL following CRC surgery is increasingly obvious [ 91 , 92 ]. Previous works on animal models have suggested the causal role of specific microorganisms presenting with high collagenolytic properties including Enterococcus faecalis and Pseudomonas aeruginosa [ 93 ].…”

Evaluation of prognostic factors and clinicopathological patterns of recurrence after curative surgery for colorectal cancer

“…While in this analysis anastomotic leak did not result in a higher risk of local recurrence, this association has been previously reported[ 30 , 31 ]. Notably, as we previously reported, the research of a relationship between gut microbiota, anastomotic leak, and local recurrence is a promising field under evaluation[ 32 ].…”

Role of gut microbiome in regulating the effectiveness of metformin in reducing colorectal cancer in type 2 diabetes

“…Interestingly, microbiota also have a substantial role in the effectiveness of chemotherapy, chemoresistance, and related side effects[ 69 ]. For instance, the presence of specific bacterial species such as Slackia and Blautia obeum may act as microbial markers associated with drug resistance monitoring[ 70 ].…”