“ Collectively, these discoveries redefine the microbiome as an active therapeutic partner rather than a passive bystander. ”
BUFFALO, NY – September 28, 2026 – A new editorial was published in Volume 17 of Oncotarget on September 23, 2026, titled “ Gut feeling: Microbes at the heart of cancer therapy .”
The article examines how the human microbiome may influence cancer development, treatment response and emerging precision-oncology strategies.
The editorial was led by first author Uzma Saqib, with Krishnan Hajela serving as corresponding author. Hajela is affiliated with the School of Life Sciences, Devi Ahilya Vishwavidyalaya, Takshashila Campus, Indore, Madhya Pradesh, India .
The microbiome—the collection of microorganisms living in a particular environment—has increasingly been linked to cancer biology. The gut microbiome can influence inflammation, immune responses and metabolism, while microbial metabolites can affect systemic metabolism, epigenetic processes and immune surveillance. Dysbiosis, or an imbalance in microbial communities, has been associated with several cancers. The authors highlight Fusobacterium nucleatum in colorectal cancer and Helicobacter pylori in gastric cancer as examples of microbes associated with tumor-promoting processes.
The microbiome may also affect how patients respond to cancer therapy. The editorial discusses evidence linking favorable gut microbial profiles with responses to immune checkpoint inhibitors such as anti-PD-1 and anti-CTLA-4 therapies. Certain microbial communities may support dendritic-cell maturation, T-cell priming and antitumor immunity, whereas dysbiosis has been associated with treatment resistance. Microbial metabolism can also influence chemotherapy efficacy and gastrointestinal toxicity.
These findings have encouraged investigation of the microbiome as both a therapeutic target and a biomarker. Microbial signatures may potentially help predict responses to immunotherapy, while probiotics, prebiotics and fecal microbiota transplantation are being explored as ways of modifying treatment response. The authors highlight Akkermansia muciniphila , which has enhanced anti-PD-1 efficacy in preclinical models. These approaches remain investigational and are not established replacements for standard cancer treatments.
The editorial also examines more direct interactions between microbes and cancer treatment. Bacteria residing within tumors can produce 2-methylisocitrate (2-MiCit), a metabolite reported to sensitize tumor cells to chemotherapy. The paper describes evidence that 2-MiCit disrupts mitochondrial metabolism and induces DNA damage, potentially lowering the threshold for chemotherapy-induced cell death and enhancing the effects of agents such as 5-fluorouracil in experimental models.
Another experimental approach involves introducing defined bacterial communities into tumors. The authors discuss a combination of non-pathogenic Proteus mirabilis and Rhodopseudomonas palustris that has been shown to reduce tumors in experimental models. Proposed mechanisms include vascular collapse and thrombosis leading to tumor necrosis, along with intratumoral biofilm formation and metabolic stress. These findings remain preclinical and require further investigation before their relevance to human cancer treatment can be established.
The paper also highlights microbial extracellular vesicles (mEVs), small membrane-bound particles that transport biologically active molecules between microbes and host cells. Bacterial outer membrane vesicles are being investigated for drug delivery and immune modulation. Preclinical studies suggest that engineered or commensal-derived microbial vesicles may influence tumor growth, T-cell infiltration and treatment response, including potential synergy with anti-PD-1 immunotherapy. However, microbial vesicles can have both pro- and antitumor effects depending on their source and biological context.
Microbial extracellular vesicles are also being explored as potential biomarkers for cancer detection, disease monitoring and treatment-response prediction. Clinical translation will require standardized isolation methods, control of immunogenicity and endotoxin content, reliable tumor targeting and appropriate regulatory frameworks.
Despite growing interest in microbiome-based cancer strategies, significant limitations remain. Microbiome composition varies with genetics, diet, lifestyle, geography, medications, disease stage and tumor type, while differences in sample collection, sequencing and bioinformatic methods can contribute to inconsistent findings. Establishing causality is another major challenge because cancer-associated microbial changes may be drivers of disease, consequences of tumor-associated changes or biological bystanders.
Substantial person-to-person variation may also lead to different responses to microbiome-based interventions. In addition, studying microbes located directly within tumors is technically challenging because of low microbial biomass and susceptibility to contamination. The authors therefore emphasize standardized protocols, multicenter longitudinal studies, multi-omics approaches and stronger validation of microbiome-derived biomarkers.
“ Patient-specific microbiome profiling combined with engineered microbial therapeutics, may clear the path for the development of safe and effective strategies for precision oncology .”
Overall, the editorial presents the microbiome as more than a passive feature of cancer biology. Microbial communities, metabolites and extracellular vesicles may influence tumor development, immune activity and treatment response while offering potential avenues for biomarkers and therapeutic intervention. However, much of the therapeutic evidence remains preclinical, and questions involving causality, individual variability, standardization and safety must be resolved before microbiome-based approaches can become established components of precision oncology.
DOI: https://doi.org/10.18632/oncotarget.28919
Correspondence to: Krishnan Hajela – hajelak@gmail.com , ORCID: orcid.org/0000-0002-4742-9643
Abstract video: https://www.youtube.com/watch?v=IDY6pK5yo-A
Keywords : cancer, gut microbiome, immunomodulation, precision therapeutics, tumor
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Gut feeling: Microbes at the heart of cancer therapy
23-Sep-2026
Authors have no conflicts of interest to declare.