Year: 2026
Type: editorial
Abstract: also affects host metabolism, causing the reduction of protective short-chain fatty acids like butyrate and accumulation of secondary bile acids, lactate, and polyamines that support tumorigenesis These mechanisms are different for each kind of cancer. Fusobacterium nucleatum has been associated with promoting colorectal cancer development through FadA-mediated E-cadherin/β-catenin signaling and mediated activation of TIGIT receptor expressed on immune cells, helping the cancer to evade the immune system. Similar associations can be found in Fusobacterium nucleatum and Porphyromonas gingivalis, which can contribute to head and neck carcinogenesis by means of epithelial disruption, inflammation, and immune manipulation. For instance, the latter has been shown to induce overexpression of immune checkpoints like PD-L1 in the oral epithelium and cancer cells, possibly helping with immune escape. In prostate cancer patients, there was an increase in Methylobacterium, especially M. organophilum, in the tumor compared to the benign tissue in Indian and UAE samples. However, these associations need more evidence and remain population-specific.The microbiome also plays a role in the efficiency, toxicity and resistance to cancer treatment. Commensals producing short-chain fatty acids (SCFAs) and some metabolites like inosine or indole-3-aldehyde contribute to immune checkpoint inhibitors' efficiency, whereas dysbiosis caused by antibiotics correlates with worse treatment outcomes. β-glucuronidase enzymes of gut microbes convert irinotecan to its toxic metabolite, causing diarrhoea, and γ-proteobacteria destroy gemcitabine, making chemotherapy less effective. The βglucuronidase can deconjugate the estrogen glucuronide metabolites from the liver and produce active estrogens, which are recycled via enterohepatic recirculation. Thus, elevated β-glucuronidase enzyme activity of gut bacteria could lead to increased exposure of breast cells to active estrogens and promote estrogen receptor-positive (ER+) breast cancerhormone receptor-positive breast cancer. Moreover, microbial composition correlates with radiotherapy-induced toxicity and systemic antitumor activity.The results facts mentioned above have led to attempts to alter the microbiome using dietary interventions, prebiotics, probiotics, live biotherapeutics, and faecal transplants in order to improve therapeutic efficacy and reduce potential toxicities of treatment. However, the clinical translation is complicated by high individual variability among patients, differences in methodology of microbiome studies, and a lack of understanding of microorganisms' function. The perception of dysbiosis as a set of alterations at the level of organisms and pathways is necessary for developing targeted microbiome-based methods for cancer prevention and therapy.All of the papers published in on the topic, concern taken together, support one common idea: the microbiome does not act as a mere bystander or a simple driver of cancer development but as a complex distributed network. When this network is disrupted, a condition known as dysbiosis, it can influence inflammation, genotoxicity, immune evasion, and metabolism throughout cancer initiation and progression., whose perturbation-dysbiosis-interacts with inflammation, genotoxicity, immune escape and metabolism at each step of cancer.Lin et al. discuss that the focus is no longer on the organisms, but rather on the communication between the oral-gut axis microorganisms. Head and neck cancer (HNC) is increasingly linked to oral and gut microbiota Al Shareef et. al. investigated the prostate cancer tissue microbiota and showed that microbial diversity was significantly higher in prostate cancer samples compared to benign prostatic hyperplasia tissues, and had more variation in their microbial composition. Among the identified bacterial genera, Methylobacterium was more abundant in prostate cancer, and this association remained consistent even after adjusting for other clinical variables. showed greater microbial diversity and compositional heterogeneity than controls. Notably, the genus Methylobacterium was enriched in prostate cancer tissue. Authors are highlighting the importance of population-specific microbiome characterisation. Dixit et al.'s comprehensive review provides a good "twohit" approach: the first dysbiosis hit creates a permissive and barrier-deficient microenvironment, while the second hit -genotoxicity, persistent inflammation, immune escape, etc. drives malignant transformation.Author suggested that, however, clinical translation remains challenging because of individual variability, mechanistic complexity, and lack of standardisation. These challenges underscore the need for personalised, microbiome-informed approaches to cancer prevention and therapy.Three common points appear: methodological caution, increased mechanistic specificity and standardisation for clinical applications. The field is moving away from general "good vs bad" notions of the microbiome to specific pathways like FadA/E-cadherin, Fap2/TIGIT, colibactin/DNA damage and SCFA signalling. The challenge is now harmonisation of sampling, sequencing, functional validation, donor selection and regulatory aspects. Future progress in this field will probably use integration of multi-omic approaches and mechanisms rather than the discovery of new organisms.
Source: Frontiers in Oncology
Language: English
Topic: Gut microbiota and health
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7222942034