Probiotics, antibiotics and stewardship around immunotherapy

Meta-analyses of more than 10,000 patients find that antibiotic exposure within about 30-60 days before starting checkpoint inhibitors is associated with roughly halved overall survival (pooled HR near 1.9), consistent across lung, kidney and melanoma cohorts, though confounding by indication (sicker patients get antibiotics) is unresolvable in observational data. Over-the-counter probiotics were associated with lower microbiome diversity and worse response in the Spencer melanoma cohort; by contrast, the specific strain Clostridium butyricum CBM588 improved PFS when added to nivolumab-ipilimumab in a small randomised trial in kidney cancer (Nature Medicine 2022, n=30). The distinction between 'probiotics' as a class and specific evidence-based strains matters. Practical stewardship: avoid prophylactic or empirical antibiotics around IO initiation where safe, narrow spectrum and shorten courses, and counsel against unselected probiotic supplements.