Introduction
Immunotherapy has become a popular cancer treatment option. Numerous aspects of the gut microbiome, including taxonomic compositions, community structures, and molecular functions, are important biomarkers for anticipating immunotherapy responses and immunological-related side effects. The gut microbiota has the potential to be both a target and a biomarker for improving the effectiveness of immunotherapy. Probiotic and prebiotic supplements, dietary changes, fecal microbiota transplantation (FMT), and antibiotic delivery are methods for modifying the gut microbiome.
What Are Gut Microbiota?
The human gut microbiota is a complex microecology that consists of over 1014 different microorganisms, such as bacteria, fungi, and viruses, coexisting with the host. It is called the "second genome" of humans due to its intimate connection to the human body. The human gut microbiota is dynamic and subject to several influences, including medication, smoking, and nutrition. Establishing a dynamic equilibrium between different bacterial species in the gut microbiota is possible.
As genomics and metabolomics technologies have developed, so has the depth of research on the gut microbiome. It was discovered that the human body and gut microbiota interact and that the development and occurrence of different diseases are intimately linked to the gut microbiota. The gut microbiota significantly influences the environment of the human body. It can encourage the body to create a lot of lymphocytes and lymphatic tissues, which will help the mucosal and systemic immune systems mature and develop normally over time.
An imbalance in the gut microbiota can encourage the growth of gastrointestinal cancers, among other malignant tumors. Bacteria comprise most intestinal germs, and they can be broadly categorized into three groups: dangerous, neutral, and good bacteria. Most good bacteria in the intestines are Lactobacilli, Bifidobacteria, obligatory anaerobic bacteria, etc.
More than 99 percent of the predominant microbiota in the intestine were obligate anaerobic bacteria, primarily consisting of Bacteroides, Peptostreptococcus, and Spirillum. Common probiotics like Lactobacillus and Bifidobacteria have been shown to enhance the gut environment and positively affect immunity, metabolism, and neurological function. Most facultative aerobic bacteria and neutral bacteria are conditionally harmful bacteria. Enterobacter and Enterococcus are examples of nondominant gut microbiota that are facultative aerobes. When the microecological balance in the stomach is normal, they are harmless, but they can be hostile in other situations. Pathogenic Escherichia coli, salmonella, shigella, proteus, and vibrio cholerae are the most common gut pathogens or harmful bacteria. A high concentration of pathogenic bacteria in the human digestive system can weaken the immune system and potentially cause the production of dangerous compounds like carcinogens.
What Are the Six Main Roles of the Gut Microbiome?
Normal gut flora contributes to:
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Distinct role in the metabolism of nutrients by the host.
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Drug metabolism and foreign substances.
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Protection against infections.
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Immunomodulation.
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Preservation of the gut mucosal barrier's.
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Structural integrity.
How does Gut Microbiota Affect Cancer Immunotherapy?
The gut microbiome primarily affects immunotherapy efficacy by modulating the immune system. The gut microbiota and its metabolites may control both innate and adaptive immunity. Patients with high concentrations of Faecalibacterium had increased densities of immune cells and antigen-presenting indicators.
By inhibiting the production of PD-L2 and its binding partner, repulsive guidance molecule b (RGMb), the gut microbiota supports antitumor immunity. Coprobacillus cateniformis was determined to be the mediator responsible for this action, as it was observed to downregulate PD-L2 expression on dendritic cells (DCs) and boost the effectiveness of PD-1 (programmed cell death protein 1) inhibitors. In melanoma patients that responded to PD-1 inhibitors, the Faecalibacterium, Ruminococcaceae, and clostridiales were more prevalent. These bacteria also had a strong positive link with the infiltration of CD8+ T cells and the frequencies of effector CD4+ and CD8+ T cells in the bloodstream.
How Does Gut Microbiota Affect the Adverse Reactions of Tumor Immunotherapy?
Immune checkpoint inhibitors, the primary development concept for tumor immunotherapy, can increase the body's antitumor immunity; however, side effects can affect the pituitary, thyroid, liver, heart, lung systems, skin, gastrointestinal tract, and lungs. The gut microbiota can both lessen the side effects of immunotherapy and increase its sensitivity.
Bifidobacterium can prevent colitis brought on by Ipilimumab therapy from developing. One possible reason for reducing immunotherapy's side effects could be the Bifidobacterium species' inhibition of proinflammatory cytokines. They discovered that the aforementioned mixed strains might increase the generation of CD8+ T lymphocytes by interferon γ via the major histocompatibility class IA molecular pathway and CD103+ dendritic cells. It also prevents treatment-related enteritis at the same time.
Conclusion
The term "microbiota" refers to all microorganisms, including bacteria, archaea, fungi, and viruses, that coexist in a certain environment, such as the skin, digestive system, mouth, vagina, or eyes. The intestine contains most of the human body's bacteria, which are the gut or intestinal microbiota. Providing nutrients, vitamins, toxins, and catabolic medications, as well as shielding the body from infections, fostering the growth of the immune system, and preserving epithelial mucosal homeostasis, are just a few of the physiological roles intestinal microbes play in preserving the host's health. The microbiota significantly influences the physiology and pathophysiology of the human body. According to estimates, microbial infections cause 10 to 20 percent of cancer cases. Numerous investigations have indicated that the gut microbiota is a key player in cancer development. Microbes and their products can either directly cause cancer or prevent it from starting and spreading through the control of circulating metabolite production, inflammation, and immunological responses. Immunotherapy for cancer is a very promising treatment that works by stimulating the immune system to destroy cancer cells and stop the growth of tumors. The microbiota present can influence immunotherapy responses in the human body.
