Trust your gut: how your gut microbiota can save you from cancer

Unhealthy dietary habits, sedentary lifestyles, smoking, and alcoholism, have long been flagged as culprits for several physiological disorders, including colorectal cancer (CRC) occurring in the colon or rectum in the digestive tract. The human intestinal tract consists of a variety of microorganisms, called “gut microbiota,” which affect the physiological and pathological functions inside the body. Normal gut microbiota helps maintain healthy intestinal conditions, including the gut barrier that blocks the passage of harmful entities from the intestine into the body, and immune cells that control the growth and mutation of cancerous cells. Several studies link modern unhealthy habits with disruptive changes in the gut microbiota, which can lead to chronic inflammation, DNA or chromosomal damage, and other harmful effects, all of which can stimulate the development and malignancy of CRC and influence its prognosis.

There is a growing interest in understanding how gut microbiota modulation impacts CRC detection and development, and the opportunities it presents for microbe-based therapeutics for CRC treatment and prevention. To supplement this growing body of research, a recent review published in the Chinese Medical Journal summarizes the pathogenic and anticancer mechanisms of CRC-related bacteria and describes new bacteria-dependent therapies for effective CRC management.

Talking about the main objective behind the review, Dr. Jie Hong, corresponding author of the study, says, “CRC is one of the leading cancers in China, with a significant increase in new cases and disease-related mortalities observed since 2015. We hope that our review facilitates clinical applications of intestinal bacteria for preventing and treating CRC.” 

The study explored the effects of common CRC-related bacteria on mice models and classified them based on their influence on CRC development as “direct” and “indirect” carcinogenic bacteria, which promote CRC advancement directly or through secondary effects on the intestine and immunity, respectively, and “probiotics,” which include bacteria that are beneficial for intestinal health and may exhibit anticancer properties.

In a healthy gut, the number of pathogenic bacteria is usually insignificant to exert any serious harmful effects. However, when the intestinal health is compromised (such as during illnesses or due to overuse of antibiotics), these pathogenic bacteria can rapidly invade and disrupt the gut microbiota balance, and stimulate CRC development through different mechanisms. Some bacteria, including Enterotoxigenic Bacteroides fragilis, certain strains of Escherichia coli, and Campylobacter jejuni, produce toxins that damage the intestinal epithelium, a key component of the gut barrier, and can lead to inflammation, infection, and cancer formation.

Other bacteria, such as Streptococcus. bovis and Fusobacterium nucleatum, can stimulate CRC cell proliferation and increase its invasiveness and resistance to chemotherapy. Peptostreptococcus anaerobius can promote the generation of reactive oxygen species or free radicals that can damage DNA, proteins, and cell metabolism, stimulating CRC development.

On the other hand, probiotics prevent cancerous cell proliferation and produce anticancer substances while reducing cancer-promoting substances. Akkermansia muciniphila, an anticancer probiotic, decreases inflammation in the colon and has proven effective in restoring the efficacy of immunotherapies. Lactobacillus rhamnosus GG and Pediococcus pentosaceus, both lactic acid bacteria, have antitumor capabilities and can prevent CRC development. Streptococcus thermophilus prevents gut microbiota infection and produces beta-galactosidase, an enzyme essential for reducing colonic cancer development. Similarly, Clostridium butyricum and Bacillus subtilis are anti-inflammatory and can reduce CRC cell proliferation and promote the degeneration of cancerous cells while enhancing immune response.

Working together with probiotics are prebiotics and postbiotics, which boost the activity of probiotics and help in metabolizing food to produce nutrients and beneficial by-products. Prebiotics are food compounds (like dietary fibers) that improve the growth of probiotics, increase micronutrient absorption, and regulate metabolism and immunity. Postbiotics, such as short chain fatty acids, are soluble factors secreted by living bacteria or released after a bacterial cell breaks down, which help restore the gut barrier, prevent pathogen translocation, diminish CRC cells, suppress bacterial toxins, and exert anti-mutagenic and antioxidant effects.

Another microbial CRC therapy gaining in popularity is fecal microbiota transplantation from healthy donors into CRC patients to restore their gut microbiota balance. Furthermore, an assorted diet comprising of probiotics, prebiotics and postbiotics is encouraged as a practical and economical remedy to manage CRC. Traditional Chinese medicine, which includes ingredients such as curcumin, is one such special diet that can regulate intestinal microbiota, improve immunity, and prevent CRC development.

Overall, the sentiment conveyed in the review is that microbe-based studies are important biomarkers for CRC, and gut-microbiota modulation is a promising approach for CRC prevention and treatment. Voicing the team’s collective vision for the future, Dr. Hong says, “Further clinical research on intestinal microbiome should clarify more specific bacteria related to CRC development and focus on potential applications of microbe-oriented therapies along with strategies to broaden the scope of CRC management”. 

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Reference

DOI: https://doi.org/10.1097/CM9.0000000000001887