Could the key to efficient chemotherapy lie in our gut? Read along to find out.
Reading time: 6 minutes
Yousra Iftequar
Cancer is a word that carries weight, fear, and urgency. It’s a disease that has touched nearly every family, leaving behind stories of resilience, loss, and medical breakthroughs. As one of the leading causes of illness and death worldwide, its impact is only expected to increase, with projections suggesting 29.4 million cases by 2040.
For decades, chemotherapy has been the backbone of cancer treatment. These powerful cytotoxic drugs work by attacking rapidly dividing cancer cells, but because they don’t discriminate, healthy cells, particularly those in the bone marrow, digestive system, and hair follicles, also get caught in the crossfire.
As our understanding of cancer treatment deepens, attention has shifted beyond just the tumor itself to the patient’s internal environment, particularly the gut microbiome. The gut’s microbial community is now recognized as a critical player in overall health, immunity, and even in determining how patients respond to chemotherapy. Emerging research suggests that the gut microbiota may influence the effectiveness and side effects of cancer therapies, opening new avenues for improving patient outcomes.
How Does the Gut Microbiome Influence Chemotherapy?
The human intestinal microbiota is a complex microcosm composed of more than 1000 different bacterial species, archaea, fungi, and viruses. There is growing evidence that these microbial inhabitants are not only involved in the digestion and absorption of food, but they can also exert a protective function by preventing the adherence of pathogenic bacteria to the mucosal layer, and they play a pivotal role in modulating the innate and acquired immunity of the host. In recent years, the gut microbiome has emerged as a major focus in cancer research, shifting the way we think about treatment response and drug effectiveness. Scientists are now uncovering its influence on chemotherapy and drug metabolism, a field known as pharmacomicrobiomics.
Why does this matter? The gut microbiota doesn’t just coexist with us; it actively participates in metabolic, immune, and inflammatory pathways that impact cancer progression and treatment. In fact, gut bacteria have been known to activate certain drugs since the 1960s, but only recently have advanced sequencing technologies allowed us to truly appreciate the depth of these interactions.
Scientists are now exploring how gut bacteria interact with various chemotherapy drugs, including 5-fluorouracil, cyclophosphamide, irinotecan, oxaliplatin, gemcitabine, and methotrexate, as well as targeted immunotherapies like anti-PD-L1 and anti-CTLA-4 treatments. The way these microbes influence drug action is structured under the TIMER framework, which includes:
- Translocation: Movement of bacteria or their components beyond the gut, influencing immune responses.
- Immunomodulation: Regulating how the immune system responds to cancer and treatment.
- Metabolism: Modifying drugs before they take effect.
- Enzymatic degradation: Breaking down chemotherapy agents, altering their potency.
- Reduced diversity: Changes in gut bacteria that affect drug response.
Probiotics and Prebiotics in Cancer Therapy: A New Frontier?
While much research has focused on how the existing gut microbiota can influence the response to chemotherapy, scientists are also increasingly exploring ways to actively modulate the gut environment to improve cancer outcomes. Among these strategies, the use of probiotics and prebiotics has gained significant attention.
Probiotics
Probiotics are defined as “live microorganisms that, when administered in adequate amounts, confer health benefits to the host.” Probiotics have been used by humans for centuries. They naturally occur in dairy and dairy products, which serve as a rich source for many of these beneficial microorganisms, including members of the genera Lactobacillus, Bifidobacterium, and Saccharomyces.
One of the primary ways probiotics influence cancer risk is through their ability to bind to, degrade, and inhibit the activity of mutagens (agents that cause changes in DNA), thereby reducing their carcinogenic potential. Additionally, probiotics play a crucial role in modulating the metabolism of procarcinogens — substances that, in themselves, are not cancer-causing but can be converted by the body into active carcinogens. Beyond detoxification, probiotics also help shape the gut environment in ways that may protect against cancer. Through the fermentation of non-digestible carbohydrates, they produce short-chain fatty acids (SCFAs) such as butyrate, which lower gut pH and create an environment less favorable for harmful bacteria and cancer-promoting pathways. Perhaps most significantly, probiotics have been found to modulate and enhance the host’s immune system. Probiotics have been extensively researched for their role in chemotherapy-induced mucositis, particularly those from the genera Lactobacillus and Bifidobacterium.
Next-generation probiotics: Do they open new therapeutic strategies for cancer patients?
There is increasing interest in next-generation probiotics (NGPs) as potential therapeutic agents capable of modifying gut microbiota and influencing cancer development. Three emerging NGPs include Faecalibacterium prausnitzii, Akkermansia muciniphila, and Bacteroides fragilis, whose presence in the digestive system may play a significant role in cancer incidence.
They have been shown to strengthen the immune system, support gut microbiota activity, and protect against leaky gut by preserving intestinal barrier integrity. Additionally, F. prausnitzii may help alleviate gastrointestinal side effects associated with chemotherapy and radiotherapy, while A. muciniphila has the potential to enhance the effectiveness of immunotherapy.
Prebiotics: Fueling the Right Bacteria
Prebiotics are non-living dietary components that contribute to host health by selectively stimulating the growth or activity of specific beneficial microorganisms in the colon. Primarily composed of dietary fibers, these carbohydrates remain undigested as they pass through the digestive system, reaching the large intestine, where they undergo fermentation by resident gut bacteria. This fermentation process leads to the production of SCFAs, which help lower intestinal pH and create an environment that supports the proliferation of beneficial bacteria, such as Lactobacillus and Bifidobacterium.
Future Prospects
Microbiome-based therapies, including prebiotics, probiotics, fecal microbiota transplantation (FMT), and microbiome-targeted drug delivery systems, hold promise for transforming cancer treatment by boosting therapeutic effectiveness, minimizing adverse effects, and enhancing patient outcomes.
• Personalized microbiome-based therapies: Using microbiome profiling to tailor probiotic or prebiotic interventions for individual cancer patients.
• Microbiome-derived drugs: Developing postbiotic compounds (metabolites from beneficial bacteria) that can be used in treatment.
• Fecal microbiota transplantation (FMT) in oncology: Early studies suggest that FMT from responders to non-responders could improve immunotherapy efficacy.
Final Thoughts
The gut microbiome represents an exciting frontier in oncology, offering new opportunities to improve cancer outcomes through diet, probiotics, and prebiotics. While much research is still needed, the potential to enhance chemotherapy, immunotherapy, and overall patient well-being makes this a promising area of investigation. By harnessing beneficial microbes, we may be able to enhance cancer therapies, reduce side effects, and improve patient prognosis.
Header Image Source: Image generated by author, with assistance from ChatGPT by OpenAI.
Edited by Mariella Careaga
References
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