Probiotics and Colorectal Cancer – Potential Chemoprotective Mechanisms

Utilising an experimental model in rats, a recent study has identified how probiotic intake may help prevent colorectal cancer initiation.

Colorectal cancer (CRC) is the third most common cancer worldwide, so although incidence has remained stable in the UK and US since the mid-1990s, CRC remains an incredibly common cancer. Moreover, CRC incidence and mortality are rapidly increasing in less-developed countries, predicting a global 60% increase in new CRC cases by 2030.

Chemotherapy and radiotherapy are limited by the varying post-treatment rates of CRC recurrence and disease-free survival, prompting great attention towards preventative measures to decrease CRC cancer risk. There are ever-growing findings suggesting that dietary supplementation with probiotics can help prevent CRC carcinogenesis. Many mechanisms for this link have been theorised, but their significance remains largely unknown.

The Research

I wouldn’t blame you for rolling your eyes at yet-another story highlighting the health benefits of probiotics, but a recent research study from India gives exciting evidence for exactly how probiotics could be chemoprotective.

Walia et al. adopted a widely-used animal model of CRC whereby rats injected with 1,2-dimethylhydrazine (DMH) develop colorectal tumours. Crucially, the development of tumours in this experimental model and in human colon carcinomas share similarities regarding excessive cellular proliferation and genomic alterations. Previous studies have indicated that probiotics prevent DMH-induced colon tumour formation. The study conducted by Walia et al. aimed to determine the molecular mechanisms responsible for probiotic-mediated prevention of DMH-induced carcinogenesis.

The Results

Oxidative stress refers to the buildup of harmful free radicals and ‘reactive oxygen species’ without their damaging effects being counterbalanced by the human body. Great oxidative stress can result in gene mutations and alteration of cellular signalling, placing it as a highly important factor in cancer development. Walia et al. demonstrated that DMH-treated rats given a lactobacillus-based probiotic significantly reduced the levels of a well-established marker for oxidative stress compared to the DMH-only control group. These results support previous findings that show probiotics to reduce the negative effects of oxidative stress. Furthermore, antioxidants inhibit oxidative stress, and Walia et al. found that probiotic supplementation caused a significant increase in certain antioxidant enzymes in DMH-treated animals.

Walia et al. then investigated more specific cellular and molecular effects that probiotics may be exerting in the DMH-induced colon cancer model, and centred their efforts around p53. In normal cells, the p53 protein delivers a crucial anticancer role as it activates DNA-repair mechanisms, or initiates apoptosis for cells with irreparable DNA. Mutations in p53 allow cells to grow and divide in an unregulated fashion and can therefore lead to tumour formation. In DMH-treated animals, Walia et al. observed that p53 activity was significantly reduced. Conversely, proper p53 activity was restored in rats given probiotic in addition to DMH, suggesting that probiotics help to maintain DNA integrity in colon tissue.

In summary, the results obtained by Walia et al. indicate that Lactobacillus-based probiotics protect against colorectal cancer formation due to their antioxidative properties and maintenance of DNA repair.

My conclusions

The link for probiotics in preventing CRC has been made by numerous in-vitro, in-vivo and gut microbiome studies. However, I believe this simple but effective investigation was an important forward step in identifying the underpinning mechanisms and thus further reinforcing previous findings.

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