Exploring the Dynamic Interplay Between the Human Micro-Biome and Cancer Development, Progress and Therapy

Introduction : The human microbiome is essential for both promoting health and preventing the onset of disease. The complex association between the microbiome and cancer has been clarified by recent research, which has important ramifications for cancer diagnosis, prevention, and treatment. With an emphasis on possible causes and a discussion of treatment options, this review seeks to investigate the dynamic interplay between the microbiome and the development of cancer. Objective: This review aims to explore in detail the complex connection between the human microbiome and the development of cancer. Methodology: We looked through English-language publications from 2015 onward on Web of Science, PubMed, Medline, Embase and Google Scholar for research on the relationship between the human microbiome and the development of cancer. Conclusion: There exist numerous ways by which the human microbiome is crucial to the pathogenesis of cancer.


Introduction
The intricate ecology of bacteria called the human microbiome, which lives in and on our bodies, has come to be recognized as essential to preserving health and modifying the course of disease [1] .Advances in microbiome research have revealed its complex role in many physiological processes, such as immune control, metabolism, and neurological functions.The growing knowledge of how the human microbiome affects the onset and spread of cancer is particularly intriguing [2] .By delving into the complex interactions that exist between the human microbiome and cancer, this narrative review aims to illuminate the different aspects of this relationship.
Unchecked cell proliferation and the capacity to infiltrate neighboring tissues are characteristics of cancer [3] .Although environmental variables and genetic abnormalities have long been known to be major causes of cancer, mounting data indicates that the microbiome also has a significant impact on carcinogenesis [4] .Research has linked certain microbial species to immune system disruption, inflammatory promotion, and the production of carcinogenic compounds that can aid in the development and spread of different forms of cancer [5] .The development of gastric cancer has been associated with the bacterium Helicobacter pylori, which is known to colonize the lining of the stomach [6] .Its capacity to cause longterm inflammation and modify the stomach milieu highlights the complex relationship between carcinogenesis and microbial dysbiosis [6] .The oral cavity bacteria Fusobacterium nucleatum has been linked to colorectal cancer through immune evasion and tumor progression mechanisms [7] .
The microbiome has been linked to altering treatment responses and outcomes in addition to its function in the development of cancer [8] .Microbial makeup may have an impact on the effectiveness of standard cancer treatments including immunotherapy and chemotherapy, according to new research [9] .Microbes have the potential to shape an individual's response to therapy by influencing medication metabolism, changing a drug's bioavailability, or modifying the immune system's reaction to a treatment [10] .In the modern era of precision medicine, an understanding of these relationships is essential for enhancing treatment plans and enhancing patient outcomes [11] .
Apart from its impact on cancer metastases and treatment outcomes, the microbiome exhibits potential as a target for innovative therapeutic approaches [12] .Probiotics, prebiotics, and fecal microbiota transplantation are some of the strategies that try to modify the microbiome and may open up new possibilities for cancer prevention or treatment by reestablishing microbial balance and boosting host immune responses [13] .The significance of investigating the microbiome's function in cancer biology is emphasized by the possibility of using it as a therapeutic tool [10] .
The complex relationship between cancer and the human microbiome is a rapidly developing field of study with broad implications for oncology [14] .The purpose of this review is to go deeper into this changing field by emphasizing the crucial role that the microbiome plays in determining the course of cancer and opening the door for cutting-edge methods of individualized cancer treatment.

Micro-biome Dysbiosis and Cancer Risk
The human microbiome plays a crucial role in maintaining host health and influencing disease processes [15] .Microbiome dysbiosis, characterized by alterations in microbial composition and function, has been implicated in the pathogenesis of numerous diseases, including cancer [9] .Microbiome dysbiosis is shedding light on the mechanisms through which microbial imbalances can promote tumorigenesis [12] .
Emerging evidence suggests that dysbiosis of the gut, oral, skin, and other microbiomes can contribute to cancer development through multiple mechanisms [16] .Dysbiotic microbial communities may promote inflammation, disrupt immune surveillance, and produce genotoxic metabolites, all of which can drive cellular transformation and tumor progression [17] .Dysbiosis of the gut microbiome has been linked to colorectal cancer, with specific bacterial species such as Fusobacterium nucleatum and Escherichia coli implicated in promoting tumorigenesis through mechanisms involving chronic inflammation and DNA damage [18] .
Furthermore dysbiosis of the oral microbiome has been associated with an increased risk of oral and esophageal cancers [19] .Oral pathogens, such as Porphyromonas gingivalis and Streptococcus mutans, have been shown to induce inflammation, alter the local microenvironment and promote carcinogenesis in adjacent tissues [20] .Dysbiosis of the skin microbiome has been linked to skin cancer development with alterations in microbial diversity and composition influencing immune responses and tumor progression [21] .
In addition to promoting cancer initiation, microbiome dysbiosis can also impact cancer treatment responses and outcomes [3] .Dysbiotic microbial communities have been shown to modulate the efficacy of chemotherapy, immunotherapy and other cancer treatments through various mechanisms [22] .Certain gut microbes can metabolize chemotherapeutic agents affecting drug bioavailability and therapeutic responses [22] .Moreover, dysbiosis-induced immune dysregulation can impair antitumor immunity and limit the effectiveness of immunotherapy [10] .
Understanding the complex interplay between microbiome dysbiosis and cancer risk is essential for developing novel strategies to prevent, diagnose and treat cancer [23] .Targeting dysbiotic microbial communities through interventions such as probiotics, prebiotics, or fecal microbiota transplantation holds promise as a potential approach to modulate cancer risk and improve treatment outcomes [1] .

Microbiome-Mediated Immune Modulation
The human microbiome plays a crucial role in shaping host immune responses and maintaining health [24][5] .Microbiomemediated immune modulation refers to the intricate interactions between the microbiome and the immune system, influencing immune development, function and regulation [24] .This bidirectional crosstalk between the microbiome and the immune system is essential for maintaining immune homeostasis, protecting against pathogens and preventing inflammatory disorders [25] .The gut microbiome has emerged as a key player in modulating immune responses throughout the body [4] .The gut is home to trillions of microbes that interact with the host immune system through various mechanisms, including microbial metabolites, pattern recognition receptors, and microbial antigens [13] .These interactions help educate the immune system, shaping the development of immune cells and promoting tolerance to harmless antigens while mounting effective responses against pathogens [7] .
One of the critical roles of the gut microbiome in immune modulation is in shaping the balance between pro-inflammatory and anti-inflammatory responses [26] .Dysbiosis of the gut microbiome, characterized by alterations in microbial composition and function, can disrupt this delicate balance and lead to immune dysregulation [27] .Dysbiotic microbial communities may promote inflammation, impair immune tolerance, and contribute to the development of autoimmune diseases, allergies, and inflammatory bowel diseases [28] .
Healthy and diverse gut microbiome can support immune health by promoting the production of anti-inflammatory metabolites, enhancing barrier function, and regulating immune cell activation [29] .Certain beneficial bacteria, such as Bifidobacterium and Lactobacillus species, have been shown to exert immunomodulatory effects by stimulating the production of regulatory T cells, promoting the release of anti-inflammatory cytokines, and enhancing mucosal immunity [30] .
In addition to the gut microbiome, other body sites such as the skin, oral cavity, and respiratory tract also harbor microbial communities that interact with the local immune system [31] .Dysbiosis of these microbiomes can impact immune responses in these tissues and contribute to the development of inflammatory skin conditions, oral diseases, and respiratory infections [6] .Understanding the role of these microbiomes in immune modulation is essential for developing targeted interventions to restore microbial balance and improve immune function [29] .
Microbiome-mediated immune modulation has significant implications for human health and disease [32] .Harnessing the immuno-modulatory properties of the microbiome holds promise for developing novel approaches to prevent and treat immune-related disorders [33] .
Further research into the crosstalk between the microbiome and the immune system will pave the way for personalized approaches to enhance immune function and combat inflammatory diseases [34] .

Micro-biome-Metabolite Interactions
The composition of the gut microbiome is influenced by various factors, including diet, antibiotics and host genetics [35] .
The microbial community residing in the gut produces a wide array of metabolites through fermentation, metabolism and other biochemical processes.These metabolites include short-chain fatty acids (SCFAs), bile acids, trimethylamine Noxide (TMAO) and various neurotransmitters [36] .
Short-Chain Fatty Acids are produced by gut bacteria during the fermentation of dietary fiber [35] .They play a crucial role in maintaining gut barrier function, regulating immune responses, and influencing energy metabolism [26] .Elevated levels of TMAO have been associated with atherosclerosis and increased cardiovascular events [32] .
Gut bacteria can produce neurotransmitters such as serotonin, dopamine and gamma-aminobutyric acid (GABA), which play a role in regulating mood, cognition and behavior [37] .Dysbiotic microbiota can alter the production of metabolites, leading to systemic inflammation, insulin resistance and metabolic dysfunction [11] .

Microbiome-Derived Metabolites and Immune Modulation
Among the diverse array of metabolites produced by the gut microbiome, short-chain fatty acids stand out as key players in immune regulation [38] .Acetate, propionate, and butyrate, the major SCFAs, exert profound effects on immune cell function, promoting anti-inflammatory responses and maintaining intestinal barrier integrity [14] .These metabolites can engage with immune cells through various mechanisms, including binding to specific receptors, modulating intracellular signaling pathways and influencing gene expression [12] .SCFAs interact with G protein-coupled receptors (GPCRs) on immune cells, leading to the production of anti-inflammatory cytokines and the suppression of pro-inflammatory responses [38] .Such interactions play a pivotal role in shaping immune cell function, fostering immune tolerance, and preserving immune homeostasis [8] .

Therapeutic Opportunities
The emerging field of microbiome-based therapeutics holds promise for cancer management.Strategies such as probiotics, prebiotics, fecal microbiota transplantation (FMT) and microbial-based therapies are being explored to restore a healthy microbiome and modulate cancer-associated dysbiosis [39] .Probiotics, which are live microorganisms that confer health benefits when consumed in adequate amounts, have been studied for their potential to prevent or treat certain types of cancer [40] .Lactobacillus and Bifidobacterium species have been shown to have anti-tumor effects in animal models of colorectal cancer [16] .
Prebiotics, which are non-digestible fibers that selectively stimulate the growth and activity of beneficial bacteria in the gut, can also modulate the microbiome and potentially reduce cancer risk [17] .FMT, the transfer of fecal material from a healthy donor to a recipient, has been successful in treating certain gastrointestinal infections and is being explored as a potential therapy for cancer [12] .Microbial-based therapies, such as oncolytic viruses and bacteria, are also being investigated for their ability to enhance anti-tumor immune responses [18] .These approaches involve the use of genetically modified viruses or bacteria to selectively target and kill cancer cells while stimulating an immune response against the tumor [19] .

Conclusion
The intricate interplay between the human microbiome and cancer development highlights the significant impact of microbial communities on host physiology and immune responses.The composition of the gut microbiome, influenced by Qeios, CC-BY 4.0 • Article, May 21, 2024 Qeios ID: J0U1J3 • https://doi.org/10.32388/J0U1J35/8 various factors, contributes to the production of metabolites that can modulate immune function and inflammatory processes.Microbiome-derived metabolites, such as short-chain fatty acids, bile acids, indole derivatives, and lipopolysaccharides, play crucial roles in regulating immune responses and maintaining immune homeostasis.Dysbiosis, characterized by imbalances in the gut microbiome, can disrupt the production of immunomodulatory metabolites and lead to aberrant immune activation, potentially contributing to the development of cancer and other immune-related disorders.Understanding the mechanisms by which microbiome-derived metabolites influence immune responses is essential for developing targeted therapeutic strategies to restore immune balance and prevent cancer progression.Future research should focus on elucidating the specific interactions between microbiome-derived metabolites and immune cells in the context of cancer development.Harnessing the immunomodulatory properties of microbiome-derived metabolites holds promise for innovative approaches to cancer therapy, such as probiotics, dietary interventions, and microbial metabolite supplementation.By leveraging the dynamic interplay between the human microbiome and immune system, we can advance our understanding of cancer pathogenesis and pave the way for personalized interventions to improve cancer outcomes and overall health.