High Sucralose Intake May Lower Effectiveness of Immune Checkpoint Inhibitors in Cancer Patients: Study

The study probed the way diet affects gut microbiota and downstream immune responses in preclinical models of cancer and advanced cancer patients treated with ICI. Although the gut microbiota is known to influence cancer immunity, the particular effect of non-nutritive sweeteners was uncertain. In this research, direct evidence was given that sucralose intake altered microbial composition and decreased the pool of microbiota-accessible arginine, an amino acid necessary for T cell function.

Key Findings

• 1 shared sweetener (sucralose) profoundly changed gut microbiota composition.

• T cell metabolism and function were limited under sucralose treatment.

• Anti-PD-1 immunotherapy efficacy was decreased in preclinical cancer models and patients with advanced cancer.

• Arginine levels available to the microbiota decreased following sucralose consumption.

• Amino acid supplementation or fecal microbiota transfer (FMT) from responder mice fully restored T cell function and immunotherapy results.

The researchers isolated the biological process underlying sucralose's adverse effect. Sucralose changed microbial makeup within the gut, which then decreased the microbial pool of available arginine. Arginine is instrumental in T cell activation and metabolism. Without adequate arginine, T cells lost their functional abilities, restricting their capacity to develop effective immune responses against cancers. Restoring arginine levels—either by supplementation or microbiota transfer—restored normal T cell function and response to immunotherapy.

This research determined that sucralose intake destabilizes microbiota of the gut, decreases microbiota-accessible arginine, disrupts T cell metabolism, and eliminates response to anti-PD-1 immunotherapy. Notably, resupplementation of amino acids or microbiota transfer from responder subjects negated the adverse effects. These findings emphasize the necessity of dietary consideration in cancer therapy, as an ubiquitous artificial sweetener could perilously undermine lifesaving immunotherapies.

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