Combined immune checkpoint blockade (CICB) with agents targeting PD1 and CTLA4 can have substantial clinical benefits across many cancer types, but is associated with a high rate of immune-related adverse events (irAEs). Understanding the factors that contribute to irAE development may help prevent and treat these in patients undergoing CICB. Andrews et al. examined biomarkers of irAEs in a cohort of 77 patients with advanced melanoma receiving CICB, 49% of which experienced severe (grade ≥3) irAEs. Analysis of the microbiota in these patients identified a significant enrichment of Bacteroides intestinalis in pre-treatment samples of patients who developed severe irAEs, and a trend towards increased B. intestinalis in patients who experienced severe irAEs was also observed in an independent cohort. The authors then examined this phenomenon in a mouse model of melanoma in which CICB treatment induces intestinal inflammation. A known mechanism of intestinal inflammation by commensal bacteria involves induction of interleukin-1β (IL-1β). Accordingly, addition of an inhibitor of the IL-1β receptor (IL-1R) to CICB reduced intestinal inflammation in this model without affecting anti-tumour efficacy. Further analyses demonstrated increased Il1b expression in mouse intestines following CICB treatment, which was abrogated by antibiotic treatment, indicating a role for commensal bacteria. Colonic samples from patients who developed severe intestinal irAEs also had increased IL1B expression compared with normal colon. Finally, mice recolonized with B. intestinalis after antibiotic treatment had increased intestinal Il1b expression following CICB treatment. The mechanisms underlying the contribution of B. intestinalis to irAEs requires further elucidation, but these observations could inform clinical monitoring and treatment of irAEs.