Williams Cancer Institute

Artificial Sweeteners and Immunotherapy: Unraveling the Impact on Cancer Treatment

Artificial Sweeteners and Immunotherapy: Unraveling the Impact on Cancer Treatment

In a groundbreaking study published in the Journal for Immunotherapy of Cancer, researchers explored the connection between artificial sweeteners, specifically sucralose, and the efficacy of immunotherapy in cancer treatment. While immunotherapy has shown remarkable success in various cancers, a significant percentage of patients still do not respond to treatment, prompting investigations into potential contributing factors.

The study focused on the gut microbiota, previously linked to immunotherapy response in melanoma, and sought to understand the role of dietary factors in shaping a ‘pro’ or ‘anti’ tumor microbiome. Notably, the research uncovered that artificial sweetener, once considered inert, can disrupt the gut microbiome, potentially limiting anti-tumor immunity and the effectiveness of immunotherapy.

Using a mouse model of anti-PD1 responsive cancer, the researchers administered sucralose during tumorigenesis and anti-PD1 treatment. The results revealed a drastic reduction in anti-PD1 response in mice consuming sucralose compared to controls. This phenomenon was replicated through antibiotic treatment or fecal microbe transfer (FMT) from sucralose-treated animals, highlighting the direct impact of artificial sweeteners on treatment outcomes.

Sucralose consumption was found to diminish T cell functionality, including cytokine production, proliferation, and cell killing, while increasing T cell exhaustion within the tissue. Strikingly, the study extended its findings to human relevance, demonstrating a correlation between sucralose consumption and poor response to anti-PD1 treatment in melanoma patients.

In conclusion, this research sheds light on the significant role of artificial sweeteners in shaping the gut microbiome and impairing the response to immunotherapy. The gut microbiome was identified as both necessary and sufficient for this loss of response, suggesting that artificial sweeteners could pose a barrier to effective cancer treatment. The findings advocate for potential dietary interventions or fecal microbe transfers to enhance the response to current checkpoint inhibitors. As the study unveils a previously unrecognized factor influencing immunotherapy outcomes, it opens avenues for further exploration and personalized approaches in cancer treatment.

Additionally, it is important to note that in other studies they have implicated the natural sweetener, Stevia, to also negatively affect the microbiome. This raises caution about its use though further studies are needed.

Reference: Kristin Morder, Drew Wilfahrt, Bingxian Xie, Diwakar Davar, Hector Nieves-Rosado, Douglas Prado, Madison Nguyen, William Hawse, Larry Kane, Stacy Wendell, Jishnu Das, Greg Delgoffe, Abigail E Overacre-Delgoffe, 2 November 2023, 1322 Too sweet to be true: sucralose ablates immunotherapy response through microbiome disruption, https://jitc.bmj.com/content/11/Suppl_1/A1473

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