Microbiome Modulation of Cancer Immunotherapy Efficacy

The composition and functional capacity of the gut microbiome have emerged as critical determinants of patient response to cancer immunotherapy. Commensal bacteria and their metabolites engage both innate and adaptive immune pathways, shaping tumour microenvironments and systemic immunity. Specific taxa, notably members of the Bacteroidetes, Ruminococcaceae and Akkermansia genera, have been associated with enhanced efficacy of immune checkpoint inhibitors, while others correlate with resistance or immune-related adverse events. Microbial metabolites such as short-chain fatty acids modulate T-cell activation, dendritic‐cell function and epigenetic programmes, thereby influencing antitumour immunity. Approaches to harness this axis include dietary modulation, probiotics and faecal microbiota transplantation, as well as precision diagnostics based on metagenomic and metabolomic profiles. Together, these insights pave the way for personalised microbiota-targeted interventions to optimise immunotherapy outcomes on a global scale.

Research from Nature Portfolio

Recent studies have explored microbiome modulation to enhance immunotherapy. A 2022 randomised phase 1 trial assessed combination of nivolumab and ipilimumab with a live bifidogenic bacterial supplement in metastatic renal cell carcinoma; while the primary increase in Bifidobacterium was not significant, supplemented patients exhibited extended progression-free survival and a trend towards higher response rate, suggesting therapeutic potential of targeted bacterial consortia. In parallel, cross-cohort analyses of pretreatment stool metagenomes in melanoma patients revealed cohort-dependent associations between microbial composition and outcome following immune checkpoint blockade; a panel including Bifidobacterium pseudocatenulatum, Roseburia spp. and Akkermansia muciniphila was linked to responders, though no single species proved universally predictive, highlighting the complexity of microbial biomarkers. Foundational mechanistic work has further demonstrated that microbial metabolites such as pentanoate and butyrate can reprogramme CD8+ T cells and chimeric antigen receptor T cells via metabolic and epigenetic pathways, amplifying antitumour activity in preclinical models.

Microbiome Modulation of Cancer Immunotherapy Efficacy publication trend

The graph below shows the total number of articles in microbiome modulation of cancer immunotherapy efficacy across all publications each year (not limited to Nature Index journals).

Technical terms

Immune checkpoint inhibitors: Antibodies that block inhibitory receptors on T cells, thereby enhancing antitumour immunity.

Short-chain fatty acids (SCFAs): Microbial fermentation products (e.g. acetate, propionate, butyrate) that influence host immune and metabolic pathways.

Dysbiosis: An imbalance in the microbial community structure that can impair immune homeostasis and therapeutic responsiveness.

Faecal microbiota transplantation (FMT): Transfer of stool from a healthy donor to a recipient to restore a balanced gut microbiome.

Metagenomic sequencing: High-throughput analysis of microbial DNA from environmental samples to characterise community composition and functional potential.

References

1. Custom scoring based on ecological topology of gut microbiota associated with cancer immunotherapy outcome. Cell (2024).
2. Critical role of the gut microbiota in immune responses and cancer immunotherapy. Journal of Hematology & Oncology (2024).
3. Nivolumab plus ipilimumab with or without live bacterial supplementation in metastatic renal cell carcinoma: a randomized phase 1 trial. Nature Medicine (2022).
4. Cross-cohort gut microbiome associations with immune checkpoint inhibitor response in advanced melanoma. Nature Medicine (2022).
5. Microbial short-chain fatty acids modulate CD8+ T cell responses and improve adoptive immunotherapy for cancer. Nature Communications (2021).
6. Association of Short-Chain Fatty Acids in the Gut Microbiome With Clinical Response to Treatment With Nivolumab or Pembrolizumab in Patients With Solid Cancer Tumors. JAMA Network Open (2020).