Diet–Gut Allies Amplify Cancer Immunotherapy in Obesity

A Nature study shows that obesity-related immunotherapy responses are driven by the diet–gut microbiome axis rather than metabolic dysfunction alone. Using 12 mouse diet models, researchers found obesogenic diets foster a stable gut microbiota that can restore anti-PD-1 sensitivity after short diet changes or fecal microbiota transplantation from non-responders. Monocolonization with beneficial bacteria like Lactobacillus johnsonii, paired with an obesogenic diet, enhanced tumor regression via microbiota-derived aromatic amino acid metabolites. In human-to-mouse FMT, high-BMI donors boosted ICI efficacy versus normal-BMI donors, and an obesogenic diet could restore sensitivity after FMT from a non-responder. The work suggests diet–microbiome synergy could be leveraged to improve ICI outcomes and guide FMT-based strategies.