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Dietary sucralose impacts gut microbes, hindering cancer immunotherapy effectiveness. Restoring gut health via amino acids or fecal transplants can reverse these negative effects, improving T cell function and treatment response.

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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.