The immune system plays a major role in preventing cancer and reducing existing tumors. Immunotherapy known as anti-PD-1 is a cancer treatment protocol that works to harness and amplify natural immune repsonse. In this 2025 study from University of Pittsburg, researchers reported that mice administered the artificial sweetener sucralose (based on the human Acceptable Daily Intake of 5/mg/kg/day) experienced reduced immune function, thereby negating the benefits of immuno-therapy. Specifically, sucralose was stated to disrupt and destabilize the gut microbiota (which includes beneficial bacteria involved in immune function) resulting in compromised immune T cell function and T cell exhaustion. T cells are a type of white blood cell involved in cancer cell destruction.
ABSTRACT
Gut microbiota composition is directly associated with response to immunotherapies in cancer. How the diet impacts the gut microbiota and downstream immune responses to 55 cancer remains unclear. Here, we show that consumption of a common non-nutritive sweetener, sucralose, modifies microbiome composition, restricts T cell metabolism and function, and limits immunotherapy response in preclinical models of cancer and advanced cancer patients treated with anti-PD-1 based immune checkpoint inhibitors (ICIs). Sucralose consumption is associated with a reduction in microbiota-accessible 60 arginine, and amino acid supplementation or fecal microbiome transfer (FMT) from antiPD-1 responder mice completely restores T cell function and immunotherapy response. Overall, sucralose consumption destabilizes the gut microbiota, resulting in compromised T cell function and ablated ICI response in cancer.
Statement of Significance:
This study highlights an unappreciated role of sucralose in 65 reducing immunotherapy efficacy in both mouse models and cancer patient samples through shifts in the microbiome and arginine degradation that leads to T cell exhaustion. T cell function and immunotherapy responses are restored through amino acid supplementation.