The dietary sweetener sucralose is a negative modulator of T cell-mediated responses

Abstract

Artificial sweeteners are used as calorie-free sugar substitutes in many food products and their consumption has increased substantially over the past years1. Although generally regarded as safe, some concerns have been raised about the long-term safety of the consumption of certain sweeteners2–5. In this study, we show that the intake of high doses of sucralose in mice results in immunomodulatory effects by limiting T cell proliferation and T cell differentiation. Mechanistically, sucralose affects the membrane order of T cells, accompanied by a reduced efficiency of T cell receptor signalling and intracellular calcium mobilization. Mice given sucralose show decreased CD8+ T cell antigen-specific responses in subcutaneous cancer models and bacterial infection models, and reduced T cell function in models of T cell-mediated autoimmunity. Overall, these findings suggest that a high intake of sucralose can dampen T cell-mediated responses, an effect that could be used in therapy to mitigate T cell-dependent autoimmune disorders.

High sucralose intake suppresses autoimmunity and promotes tumor growth by limiting T cell‐mediated immune responses

“…Therefore, the consumption of sucralose has increased significantly in the past decades. These findings reported by Zani et al almost upend the way people think about sucralose 1 …”

“…In a recent study, Zani et al published an article entitled “The dietary sweetener sucralose is a negative modulator of T cell‐mediated responses” in Nature 1 . They reported that the intake of high amounts of sucralose, a calorie‐free sugar substitute, can suppress autoimmunity and promote tumor growth by suppressing the proliferation and function of effector T cells in mice.…”

“…These findings reported by Zani et al almost upend the way people think about sucralose. 1 They first treated the wild-type mice with 0.17 or 0.72 mg/mL sucralose to determine whether sucralose can affect the immune system. They did not identify any detectable effect on the homeostatic levels of immune cells, showing that sucralose had no significant effect on the immune system under immune homeostasis conditions.…”

The effect of diet and nutrition on T cell function in cancer

“…A recent study shows that dietary sucralose decreases CD8 + T cell antigen‐specific responses in subcutaneous cancer models, thus promote the tumor growth. Mechanistic studies reveal that sucralose affects the membrane order of T cells, accompanied by a reduced efficiency of T cell receptor signaling and intracellular calcium mobilization, which limits T cell proliferation and T cell differentiation 149 …”

Nonnutritive sweeteners and glucose intolerance: Where do we go from here?

“…Importantly, animal experiments have allowed unraveling some of the potential underlying mechanisms driving NNS effects on human physiology. Examples include indications of potential causal effects of some NNSs on the gut microbiome driving an altered host metabolism ( 6 ) and suppressive NNS effects on adaptive immunity in the context of cancer and infection ( 8 ). Careful consideration of the factors contributing to the above ambiguities in animal and human results may enable optimization of research toward better crystallization of NNS effects on human metabolism and associated mechanisms of activity.…”