Microbiota and immune-related adverse events in cancer immunotherapy.

This publication is a narrative review of how tissue-associated microbiomes contribute to immune-related adverse events (irAEs) from immune checkpoint inhibitors, with a primary focus on ICI-induced colitis.

Key points:

• Clinical context:

• Immune checkpoint inhibitors improve survival across multiple tumour types but can cause irAEs in non-tumour tissues (especially gut, lung, skin).
• irAEs may require ICI discontinuation and immunosuppression, creating a tension between toxicity control and preserving anti-tumour benefit.

• Role of the microbiome in irAEs:

• Emerging human and preclinical data link compositional and functional features of local microbiomes (particularly the gut microbiome) to the risk, type, and severity of irAEs.
• Certain microbial patterns appear associated with ICI colitis, while others may be protective, suggesting that microbial ecology shapes mucosal immune tone and checkpoint response.

• Mechanistic themes in ICI colitis:

• Disruption of gut barrier integrity, shifts in microbial communities, and altered microbial metabolites can promote pro-inflammatory mucosal immune responses under ICI therapy.
• The review highlights interactions between gut microbes, innate and adaptive immune populations, and checkpoint pathways that can tip the balance from effective anti-tumour immunity toward pathologic tissue inflammation.

• Therapeutic approaches under investigation:

• Strategies include modulation of the gut microbiome (e.g., antibiotics, faecal microbiota transplantation, probiotics, diet), targeted immunosuppression, and more selective blockade of inflammatory pathways.
• A central goal is to reduce irAE risk and severity without compromising systemic anti-tumour immunity.

• Implications and future directions:

• The authors emphasize the need for mechanistically informed, microbiome-focused interventions and prospective studies integrating microbiome profiling, immune phenotyping, and clinical outcomes.
• Better understanding of microbiome–immune interactions in irAEs could enable risk stratification, prevention, and personalized management of toxicity in patients receiving checkpoint blockade.