Clinical bottom line
Emerging evidence highlights the microbiome’s influential role in cancer prognosis and treatment response, particularly through modulation of the tumor immune microenvironment. Gut and oral microbiota signatures are increasingly recognized as potential biomarkers for predicting immunotherapy efficacy and disease outcomes in cancers such as hepatocellular carcinoma, ovarian, prostate, and oral cancers. While promising, clinical application is limited by heterogeneity in microbiome profiles and incomplete understanding of causal mechanisms. Integrating microbiome analysis with conventional pathology may enhance personalized oncology strategies in the near future (Huang et al., 2025; Blanco et al., 2025; Chattopadhyay et al., 2019).
What the evidence shows
Huang et al. (2025) review the gut microbiota’s role in hepatocellular carcinoma (HCC) immunotherapy, demonstrating that specific microbial taxa can remodel the immune microenvironment, influencing checkpoint inhibitor responsiveness. Modulation of gut flora through antibiotics, probiotics, or fecal microbiota transplantation shows potential to enhance treatment outcomes.
Blanco et al. (2025) discuss ovarian cancer, where tumor-associated microbiota may affect chemotherapy sensitivity and immune evasion. Their analysis suggests that microbiome-targeted interventions could improve therapeutic efficacy and prognostication.
Chattopadhyay et al. (2019) identify distinct oral microbiome signatures correlated with oral cancer diagnosis and prognosis, proposing microbial profiling as a noninvasive adjunct to histopathology.
Huang et al. (2026) further explore the gut microbiome in prostate cancer, linking microbial dysbiosis with tumor progression and treatment resistance, and highlighting opportunities for microbiome-informed therapeutic strategies.
Fessler et al. (2019) provide a broader perspective on microbiome influences in cancer immunotherapy, emphasizing the microbiota’s role in modulating systemic immune responses and treatment toxicity.
Liu et al. (2022) elaborate on gut-brain axis interactions, underscoring microbiome-mediated systemic effects that may indirectly impact cancer progression and patient well-being.
Caveats and uncertainty
Microbiome composition varies widely among individuals and is influenced by diet, environment, and medications, complicating biomarker standardization.
Causal relationships between specific microbes and cancer outcomes remain largely associative, requiring mechanistic validation.
Interventional studies manipulating the microbiome are limited and often small-scale, with inconsistent methodologies.
Potential risks of microbiome modulation, including infection or unintended immune effects, need careful evaluation.
Integration of microbiome data into clinical decision-making lacks standardized protocols and regulatory frameworks.
How this may change practice
Pathologists and oncologists should consider microbiome profiling as an emerging biomarker to complement molecular and histopathological analyses.
Microbiome-informed patient stratification may optimize immunotherapy selection and predict adverse events.
Future clinical workflows may incorporate microbiome modulation strategies (e.g., probiotics, antibiotics, fecal transplantation) as adjuncts to conventional cancer therapies.
Interdisciplinary collaboration between microbiologists, pathologists, and oncologists will be critical to translate microbiome science into practice.
Ongoing research and clinical trials will clarify the utility and safety of microbiome-targeted interventions in oncology.