Antibiotics are the most commonly prescribed drug class globally, yet their long-term consequences beyond infection control have received comparatively little attention. The possibility that disrupting the gut and urinary microbiome through repeated antibiotic courses could meaningfully shift cancer risk reframes how clinicians and patients might weigh antibiotic stewardship decisions beyond antibiotic resistance alone.
This umbrella review — a synthesis of existing meta-analyses and systematic reviews — pooled evidence across 66 distinct associations spanning 14 cancer types, drawing from searches across PubMed, Embase, Cochrane Library, and Web of Science through November 2025. Using random-effects models and the GRADE credibility framework, the authors identified nine associations reaching "highly suggestive" evidence status. Of these, antibiotic exposure was associated with elevated risk for four malignancies: proximal colon cancer, pancreatic cancer, kidney cancer, and bladder cancer. Seven additional associations were rated as suggestive, and 21 as weak, underscoring the heterogeneity of effects across cancer sites.
The cancer-type specificity here is analytically important. Proximal colon cancer and pancreatic cancer, in particular, share anatomical proximity to regions where gut microbiome perturbation would be most mechanistically plausible — Firmicutes and Bacteroidetes imbalances, reduced short-chain fatty acid production, and altered bile acid metabolism are each candidate pathways. Kidney and bladder associations may involve urinary microbiome disruption or systemic immune modulation. However, umbrella reviews inherit the limitations of their constituent meta-analyses: observational confounding (sicker patients receive more antibiotics), dose-response data that is inconsistently reported, and the inability to establish causality. The GRADE ratings of "highly suggestive" fall well short of confirmatory. This work is best understood as a credible hypothesis-sharpening exercise rather than a clinical alarm — but one that meaningfully elevates the case for prospective mechanistic research and cautious antibiotic prescribing.