Sucralose Consumption Ablates Cancer Immunotherapy Response through Microbiome Disruption

Area of Science:

• Oncology
• Immunology
• Microbiome Research

Background:

• Gut microbiota composition influences cancer immunotherapy response.
• The impact of diet, specifically non-nutritive sweeteners, on this relationship is not well understood.

Purpose of the Study:

• To investigate how sucralose consumption affects gut microbiota.
• To determine the downstream effects on T cell function and immunotherapy efficacy in cancer.
• To identify potential interventions to restore immunotherapy response.

Main Methods:

• Preclinical cancer models and advanced cancer patients treated with anti-PD-1 immune checkpoint inhibitors (ICIs).
• Analysis of microbiome composition and T cell metabolism.
• Intervention studies involving amino acid supplementation and fecal microbiome transfer (FMT).

Main Results:

• Sucralose consumption altered gut microbiota composition.
• Sucralose intake restricted T cell metabolism and function, leading to reduced ICI response.
• A reduction in microbiota-accessible arginine was observed with sucralose.
• Amino acid supplementation or FMT from responders restored T cell function and immunotherapy response.

Conclusions:

• Sucralose destabilizes the gut microbiota, compromising T cell function.
• Sucralose consumption significantly ablates anti-PD-1 immune checkpoint inhibitor response in cancer.
• Targeting gut microbiota and metabolic pathways presents a strategy to enhance cancer immunotherapy.