Targeting Gut Microbial Biofilms-A Key to Hinder Colon Carcinogenesis?

Abstract

Colorectal cancer (CRC) is a global public health issue which poses a substantial humanistic and economic burden on patients, healthcare systems and society. In recent years, intestinal dysbiosis has been suggested to be involved in the pathogenesis of CRC, with specific pathogens exhibiting oncogenic potentials such as Fusobacterium nucleatum, Escherichia coli and enterotoxigenic Bacteroides fragilis having been found to contribute to CRC development. More recently, it has been shown that initiation of CRC development by these microorganisms requires the formation of biofilms. Gut microbial biofilm forms in the inner colonic mucus layer and is composed of polymicrobial communities. Biofilm results in the redistribution of colonic epithelial cell E-cadherin, increases permeability of the gut and causes a loss of function of the intestinal barrier, all of which enhance intestinal dysbiosis. This literature review aims to compile the various strategies that target these pathogenic biofilms and could potentially play a role in the prevention of CRC. We explore the potential use of natural products, silver nanoparticles, upconverting nanoparticles, thiosalicylate complexes, anti-rheumatic agent (Auranofin), probiotics and quorum-sensing inhibitors as strategies to hinder colon carcinogenesis via targeting colon-associated biofilms.

Keywords: chemoprevention; colorectal cancer; gut biofilm; microbiota; quorum-sensing.

Figure 1

The role of colonic microbiota and biofilm in colorectal cancer (CRC) carcinogenesis. (A) The driver-passenger model for CRC carcinogenesis [39]. (B) Biofilm-driven CRC carcinogenesis. Biofilm results in loss of colonic epithelial cell E-cadherin (consistent with disrupted intestinal barrier function), increased IL-6 expression and STAT3 activation. These microbial biofilms contribute to a pro-oncogenic and pro-inflammatory state, coupled with the increased polyamine metabolism in colonic tissues, hence resulting in dysbiosis and onco-transformation and leading to tumor progression [11]. (C) The reassociation experiment showing that the microbiota communities from human biofilm-positive mucosa (healthy or CRC patients) resulted in CRC development in a new cohort of mice, indicates these biofilm-positive microbiota communities maintained their tumorigenic capacity [6].

Figure 2

Potential mechanisms of probiotics to target gut microbial biofilms.