Kimia Sadat Esfahani,1Fatemeh Nafian,2,*Tina Illeslamlo,3
1. Department of Genetics, Faculty of Advanced Sciences and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran, k.esfahani@student.iautmu.ac.ir, ORCID: 0009-0004-0809-4096 2. Department of Medical Laboratory Sciences, Faculty of Paramedics, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran, f.nafian@iautmu.ac.ir, ORCID:0000-0002-0622-4086 3. Department of Genetics, Faculty of Science, Central Tehran Branch, Islamic Azad University, Tehran, Iran, illeslamllo.tina@gmail.com, ORCID: 0009-0003-4913-590X
Introduction: Numerous cancer types cause the death of 7.5 million individuals annually. Recent approaches have been developed to enhance tumor prognoses. Nonetheless, certain cancers continue to have unfavorable prognoses due to factors namely metastasis when diagnosed and limited treatment efficacy. These come with the persistent multiplicity of cancer-related fatalities. Bacteria maintain a persistent presence within the human body throughout its lifespan and beyond. The historical interconnection between the development of human diseases like cancer and the evolution of microorganisms, mainly bacteria, is widely interesting. A significant milestone involves recognizing that an altered microbiome is a notable hallmark of cancer. Consequently, the investigation of the microbiome alteration holds substantial promise as a subject of cancer research. The current study aims to review the microbiome as a therapeutic and diagnostic target in cancers.
Methods: An estimated population of 10^13 to 10^14 microbiota inhabit the gastrointestinal tract, despite other sterile tissues. The genetic material contained within the microbiome surpasses the extent of the human genome. It has been proposed that microbiome communities can impact on development, progression, formation of metastases, and responses to treatment of diverse cancer types. Furthermore, the interconnection between the microbiome and cancer metastasis can be a positive or negative relationship. Mounting evidence substantiates the premise that the gut microbiota can modify the immune system, given its role in harboring over half of the body's lymphocytes, potentially impacting the dissemination of cancer. On the other hand, the microbiome is thought to impede cancer metastasis through its anti-inflammatory attributes. Even, interventions targeting the structure of microbial metabolites can obstruct both the early and late stages of cancer metastasis. Concisely, it has been substantiated that the initiation and progression of cancer can be influenced by dysbiosis of the microbiome.
Results: Critical roles in the metastasis of breast cancer, melanoma, prostate cancer (PC), and colorectal cancer (CRC) are played by microbiomes like Fusobacterium nucleatum(Fn), Porphyromonas gingivalis, and Akkermansia, as well as microbial metabolites including indole-propionic acid (IPA), cadaveric amines, and sodium butyrate (NaB). Metastasis promotion through inducing epithelial-mesenchymal transition (EMT) and activating the Wnt signaling pathway is facilitated by the microbiome, which, in turn, reduces β-linked proteins. Additionally, the microbiota upregulates E-cadherin expression through multiple mechanisms, impeding the EMT process. Moreover, intestinal microbiota-produced cadaveric amines suppress EMT, leading to the inhibition of cancer stem-cell motility and metastasis, thereby exerting a tumor-suppressive impact on breast cancer. A strong negative correlation was observed between the presence of Oscillatoria and the genes associated with promoting EMT, which is suggestive of potential metastasis inhibition in muscle-invasive bladder cancer (MIBC). The utilization of 16S RNA sequencing on lung tissue indicated a close relationship between the levels of Bacteriaceae, Trichospiraceae, and Ruminococcaceae within lung tissue and the risk of lung cancer, besides the survival outcomes of recurrence-free and disease-free survival among individuals diagnosed with lung cancer. A significantly higher abundance of F. nucleatum was observed in patients with CRC and its associated precancerous lesions compared to the control group. Moreover, F. nucleatum levels were notably elevated in both cancerous and para-cancerous tissues within the context of CRC. Alterations in the F. nucleatum to Faecalibacterium prausnitzii and Bifidobacterium ratio in stool samples from CRC patients hold potential as a means to detect early-stage CRC.
Conclusion: The microbiome holds a significant place within the human body through diverse functions. Research findings indicate its pivotal involvement in carcinogenesis, a role more substantial than initially anticipated. In conjunction with therapeutic approaches, clinical trials are currently being undergone by certain genetically modified bacteria, serving as antitumor agents, antioncogenes, or immunogenic antigens. It assists the enhanced potential of these bacteria for cancer therapy. With a comprehensive understanding of the microbiome, effective diagnostic and therapeutic approaches can be developed for the prevention, detection, and treatment of cancers. The microbiome is a remarkable entity from diagnosis to cancer therapy.