مقالات پذیرفته شده در هشتمین کنگره بین المللی زیست پزشکی
Anticancer effect of antibiotics in iTM and microbiome
Anticancer effect of antibiotics in iTM and microbiome
Hanieh Alizadeh,1Mohammad Kazemi Ashtiani,2Flora Forouzesh,3Mohammad Amin Javidi,4,*
1. 1- Integrative Oncology Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran 2- Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran 2. Department of Cell Engineering, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran. 3. Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran 4. Integrative Oncology Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran
Introduction: In this essay the complex relationship between antibiotics, the microbiome, and cancer treatment, highlighting the potential benefits and risks of antibiotic use in oncology is reviewed. Central to the discussion is how the human microbiome, particularly gut microbiota, influences cancer progression and treatment outcomes. The study emphasizes the dual role of antibiotics, which can both support and hinder cancer therapies depending on their effects on microbial communities.
The Role of the Microbiome in Cancer Progression and Treatment
The human microbiome plays a pivotal role in regulating immune responses, metabolism, and cellular functions, all of which are essential in cancer development and treatment responses. Microbial communities within the gastrointestinal tract are particularly influential in modulating inflammation, immune activity, and the efficacy of cancer therapies. For instance, specific bacterial species can enhance the effects of immunotherapies by boosting T-cell activity, while others may interfere with treatment by inducing immunosuppression (1). The essay explains that variations in microbial composition within the gut or other epithelial barriers can affect both local and systemic immune responses, altering cancer progression and therapy effectiveness. This influence of microbiota on anticancer therapies is becoming increasingly recognized, with studies showing that a healthy, balanced microbiome can improve treatment outcomes in chemotherapy and immunotherapy by regulating immune responses (2).
The Dual Nature of Antibiotics in Cancer Treatment
Antibiotics are frequently used in cancer patients to manage infections due to compromised immune systems. However, while antibiotics have been shown to exhibit antitumor properties by inducing apoptosis and inhibiting cancer cell proliferation, they can also disrupt the microbiome, leading to a condition known as dysbiosis (3). Dysbiosis negatively affects the body’s immune responses, potentially diminishing the effectiveness of cancer treatments, especially immune checkpoint inhibitors (ICI). This can result in suboptimal treatment outcomes for cancer patients undergoing immunotherapy (3). The essay elaborates on how antibiotics, while beneficial in preventing infections, must be used with caution in cancer patients. By disrupting gut microbiota, antibiotics can impair the immune system’s ability to fight cancer, leading to decreased effectiveness of therapies like chemotherapy and immunotherapy. This is particularly concerning in the context of ICIs, where a balanced microbiome is critical for optimal immune function (4). Intra-tumoral Microbiome and Its Impact on Treatment
In addition to the gut microbiome, the essay explores the role of the intra-tumoral microbiome, which refers to the bacterial communities found within tumors. Although research in this area is still emerging, there is growing evidence that intra-tumoral bacteria can influence cancer progression and response to treatment. Some bacteria found in tumors can metabolize chemotherapeutic agents, reducing their effectiveness. For instance, intra-tumoral bacteria have been shown to inactivate gemcitabine, a common chemotherapy drug, thereby leading to drug resistance (5). The presence of intra-tumoral microbiota also affects immune regulation and gene expression within the tumor microenvironment. These bacteria can either enhance or suppress immune responses, impacting the effectiveness of anticancer therapies (6). Thus, understanding the role of intra-tumoral microbiota offers new opportunities to optimize cancer treatments by potentially targeting these bacteria to improve therapeutic outcomes.
Methods: Human microbiome plays a crucial role in the initiation and progression of cancer by influencing the balance between cellular proliferation and apoptosis, regulating immune responses, and affecting metabolic processes within cells. Comprehensive studies have highlighted that manipulating the microbiota could potentially enhance cancer therapies. One strategy for modulating the microbiota is the administration of antibiotics, though the effects of antibiotic use can range from beneficial to detrimental. Antibiotics may directly impact cancer cells by promoting apoptosis, targeting cancer stem cells to prevent recurrence, inhibiting cancer cell proliferation, and blocking metastasis. Alternatively, antibiotics may indirectly affect cancer cells by altering the microbiota in ways that inhibit cancer growth. Due to these effects, antibiotics are increasingly used to support cancer treatment. We identified 35 relevant articles through searches on PubMed and Google Scholar using conventional keyword strategies. These studies examined the microbiome of various human anatomical sites before and after antibiotic therapy using 16S rRNA gene sequencing. The primary goal of this study is to explore the anticancer effects of antibiotics on the microbiome and intra-tumoral microbiota.
Results: Future Research and Recommendations
The essay underscores the need for more research into the use of antibiotics in oncology, particularly how they interact with the microbiome and affect cancer therapy. Personalized antibiotic regimens, tailored to individual microbiome compositions, could minimize the negative impacts of antibiotics while preserving their therapeutic benefits. Microbiome profiling, which involves understanding the composition of a patient's microbiota, could help clinicians make more informed decisions about antibiotic use during cancer treatment (2). Additionally, microbiome-targeted interventions such as probiotics, prebiotics, and fecal microbiota transplantation (FMT) are proposed as potential strategies to restore microbial balance disrupted by antibiotics. These interventions could help enhance the efficacy of cancer therapies while reducing the risk of dysbiosis-related complications. The essay also calls for longitudinal studies to assess the long-term effects of antibiotic use on cancer recurrence, metastasis, and patient survival. Developing alternative antimicrobial strategies, such as bacteriophages and antimicrobial peptides, is another recommendation. These alternatives could reduce the risk of dysbiosis and provide effective infection management without compromising the microbiome (7).
Conclusion: Conclusion
In summary, while antibiotics remain an essential tool in managing infections in cancer patients, their impact on the microbiome demands careful consideration. The disruption of gut and intratumoral microbiota can have significant consequences for cancer progression, treatment effectiveness, and overall patient survival. The essay emphasizes the importance of personalized approaches to antibiotic use in cancer therapy and the potential of microbiome-targeted interventions to improve treatment outcomes. Through further research and a better understanding of the microbiome’s role in cancer therapy, clinicians can optimize antibiotic use, ensuring that these treatments support rather than hinder cancer therapies.