Beyond BMI: The diet-microbiome context of the obesity paradox.

Anti-PD-1 sensitivity in mice is more strongly associated with diet-microbiome-metabolite interactions than with obesity-related metabolic dysfunction, challenging BMI as a sole predictor.

• Why it matters: BMI alone fails to fully capture host biological factors influencing immune therapy responses, highlighting the need for more comprehensive biomarkers to improve treatment outcomes.
• What they did: Desharnais et al. examined diverse mouse models, analyzing the relationships between diet, microbiome composition, metabolites, and anti-PD-1 therapy sensitivity, emphasizing ecosystem interactions over obesity metrics.
• The result: Their findings suggest targeting the diet-microbiome-metabolite ecosystem could enhance anti-PD-1 efficacy independently of obesity, paving the way for novel therapeutic strategies.