Gut microbiota modulation: a tool for the management of colorectal cancer

Abstract

Colorectal cancer (CRC) is the second cause of cancer death and the third most frequently diagnosed cancer. Besides the lifestyle, genetic and epigenetic alterations, and environmental factors, gut microbiota also plays a vital role in CRC development. The interruption of the commensal relationship between gut microbiota and the host could lead to an imbalance in the bacteria population, in which the pathogenic bacteria become the predominant population in the gut. Different therapeutic strategies have been developed to modify the gut immune system, prevent pathogen colonization, and alter the activity and composition of gut microbiota, such as prebiotics, probiotics, postbiotics, antibiotics, and fecal microbiota transplantation (FMT). Even though the employed strategies exhibit promising results, their translation into the clinic requires evaluating potential implications and risks, as well as assessment of their long-term effects. This study was set to review the gut microbiota imbalances and their relationship with CRC and their effects on CRC therapy, including chemotherapy and immunotherapy. More importantly, we reviewed the strategies that have been used to modulate gut microbiota, their impact on the treatment of CRC, and the challenges of each strategy.

Keywords: Colorectal cancer; Fecal microbiota transplantation; Gut microbiota; Probiotics.

Fig. 1

Gut microbiota dysbiosis and its relationship with CRC. Dysbiosis of gut microbiota and increasing the abundance of pathogenic microbiota could promote chronic inflammation and, subsequently, cancer initiation and progression through three mechanisms, including dysregulation of immune responses, virulence factors/toxins, and metabolic products

Fig. 2

Strategies applied for modulating gut microbiota in CRC and the mechanisms of action of each strategy. Probiotics: Probiotics exert their effects on gut microbiota composition through immunomodulation, inhibition of pathogenic bacteria colonization, and enhancement of the gut barrier functions. Prebiotics: They act as gut microbiota modulatory elements through direct uptake by the intestine and exerting anti-inflammatory activities, prevention of the colonization of pathogens by interacting with them, fermentation by intestinal microbiota, and stimulation of beneficial gut bacteria. Postbiotics: They exert their tumoricidal functions through selective inhibiting tumor cells and protecting intestinal epithelium by inhibiting apoptosis in epithelial cells and increasing IgA secretion. Antibiotics: Antibiotics could deplete the intestine from harmful bacteria and preserve intestinal epithelium. FMT: This strategy helps restore the diversity of microbiota in the gut