image: Figure 1: Graphical abstract.
Surgery and anastomotic leak (AL) weaken the gut barrier function, which promotes the dissemination and implantation of colorectal cancer cells in the peritoneal cavity and distant organs. A disrupted gut barrier leads to intestinal and systemic inflammation that promote carcinogenesis and decrease survival. Activation of peroxisome proliferator-activated receptor-gamma (PPAR-γ) by 5-aminosalicylate (5-ASA) and short-chain fatty acids, derived from bacterial fermentation of dietary fibers, reinforces the gut barrier, prevents AL, decreases inflammation, and ultimately improves oncological outcomes. Abbreviations: TNF-α: tumor necrosis factor alpha; IL1β: interleukin 1 beta; IL17A/F: interleukin 17 A/F; MIP-1α: macrophage inflammatory protein 1 alpha; MIP-2: macrophage inflammatory protein 2; MCP-1: monocyte chemoattractant protein 1; IL-5: interleukin 5; IL-10: interleukin 10; IFN-γ: interferon gamma; LCN2: lipocalin 2. Green arrows indicate promotion/stimulation, red arrows indicate inhibition/prevention. Created with https://www.biorender.com/.
Credit: 2024 Hajjar et al.
“Herein we discuss how gut microbiota and microbial metabolites regulate basal inflammation levels in the gut and the healing process of the bowel after surgery.”
BUFFALO, NY- August 19, 2024 – A new review was published in Oncotarget's Volume 15 on August 14, 2024, entitled, “The gut barrier as a gatekeeper in colorectal cancer treatment.”
Colorectal cancer (CRC) is highly prevalent and a major cause of cancer-related deaths worldwide. The primary curative treatment for CRC is surgical resection of the affected bowel segment. However, postoperative complications often include a weakened gut barrier and the dissemination of bacterial proinflammatory lipopolysaccharides.
Researchers Roy Hajjar, Carole Richard, and Manuela M. Santos from Centre de recherche du Centre hospitalier de l’Université de Montréal (CRCHUM), Québec; Centre hospitalier de l’Université de Montréal (CHUM), Québec; Université de Montréal, Québec; and Institut du cancer de Montréal, Québec, discuss how gut microbiota and microbial metabolites regulate basal inflammation levels in the gut and the healing process of the bowel after surgery.
“We and others have shown in the last few years that gut microbiota influences the healing process of the bowel and the restoration of the gut barrier after surgery.”
The researchers further elaborate on the restoration of gut barrier function in CRC patients and how this potentially impacts the dissemination and implantation of CRC cells in extracolonic tissues, thereby contributing to worse survival outcomes after surgery.
“Based on our recent work, we believe that weakened gut barrier function, namely due to poor healing after surgery, leads to persistent systemic low-grade inflammation and a higher risk of local and systemic cancer recurrence.”
Continue reading: DOI: https://doi.org/10.18632/oncotarget.28634
Correspondence to - Roy Hajjar - roy.hajjar@umontreal.ca
Video short - https://www.youtube.com/watch?v=HgWx_11K6Kw
Keywords: colorectal cancer, gut microbiome, gut barrier, colorectal surgery, anastomotic leak
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Journal
Oncotarget
Method of Research
Systematic review
Subject of Research
Not applicable
Article Title
The gut barrier as a gatekeeper in colorectal cancer treatment
Article Publication Date
14-Aug-2024
COI Statement
Authors have no conflicts of interest to declare.