Artificial sweetener suppresses immunity

High doses of the artificial sweetener sucralose, which is 600 times sweeter than sugar but yields zero calories when consumed, reduce immune responses in mice. Karen Vousden and Fabio Zani have found that the agent seems to affect the signals produced by immune T cells when they activate themselves to fight infections. They haven't looked in humans yet to see if the same thing could be happening, but if it is, it might be possible to use sucralose to control certain autoimmune diseases where the immune response inappropriately turns on the body itself…

Karen - Our lab's been interested in the impact of diet on disease for quite a while now, and we've been looking at how different components of our diet might be modulated for therapy. And as you know, across the globe, the consumption of sweetners is increasing rapidly and careful studies by many regulatory agencies have shown them to be safe at the normal levels of consumption. Now our study doesn't contradict these findings, however, in recent years there have been reports that sweeteners may have more effects than previously thought. So we carried out a study to look at the effects of some of these sweeteners in mice.

Chris - And how did you do it, Fabio?

Fabio - We looked at the effect of giving sucralose to mice at very high doses, doses much higher than what a normal person would see by just consuming food and drinks containing sucralose as a part of a normal diet. We measured many physiological responses such as weight gain and other metabolic parameters, including the composition of the gut microbiome. And we didn't see any major effect in any of these physiological parameters until we tested a possible effect of sucralose on T-cells that are part of our immune system.

Chris - And just to be clear, were you comparing mice with sweetener and mice without sweetener or rival sweeteners or sweeteners that are natural sugars? I mean, what was the comparison group here?

Karen - So all of those things, we fed our mice with just water and we also fed our mice with water containing different sweeteners. What we found was that feeding mice with sucralose- but not the other sweeteners we tested -somewhat decreased their ability to properly activate T-cells. So T-cells are a major component of the immune response. So what in effect we saw is there was a dampening of the immune response. So as Fabio's just said, there was no effect of sucralose on any of the other physiological responses that we tested. Also, when we tested mice with these high doses of sucralose, we didn't see any alteration of the immune system under normal unstressed conditions. However, when we used models that would trigger an immune response that involves those T-cells in mice, we did notice that the activation of the T-cells was less effective. And importantly, all of those effects are reversible. So when we take away the sucralose, the immune response goes back to normal. Then we actually went onto test where the sucralose could have any therapeutic effect, and we looked again in mice of T-cell mediated autoimmunity. So that means autoimmunity caused by overactivation of T-cells. And so we looked in two models, a type one diabetes model and a colitis model. And we found that these very high doses of sucralose dampen the T-cell responses and reduced inflammation, which in the end was beneficial for the mouse.

Chris - Now obviously we're not advocating, Karen, that someone with those diseases should take extremely high doses of sucralose to try to control their disease. But what it might highlight, if you can work out how it's having that effect, is a novel avenue therapeutically presumably, isn't it? So do you know how the sucralose is affecting the T-cells in the way that it is?

Karen - We spent a long time trying to answer that question. It was quite difficult to answer. So in our cell culture systems, we found that, in fact, exposing T-cells to sucralose prevented them from properly activating the signals that are required to mount a proper immune response. The way that that seemed to be happening is that the sucralose seemed to be affecting the membrane dynamics of those cells. So preventing the normal clustering of the receptors that these cells have allows them to signal downstream to properly activate the T-cell and thus activate the T-cell immune response.

Chris - So Fabio, do you think that this is clinically relevant? It's very interesting academically and at the doses you gave it - very, very high doses in the mice you saw this effect, but does this have impacts for clinical medicine and also the consumption of these sorts of sweeteners for people more broadly?

Fabio - So we don't know whether we would see the same effect in humans, and we are now hoping to test whether high doses of sucralose could have a similar effect in people. We really want to emphasise that our study did not support the idea that normal sucralose consumption is immunosuppressive. We need very high doses indeed. In our study we use two different doses of sucralose and both these doses are very, very high. And the lowest of the two doses already shows some decreased ability in modulating T-cell responses. That prompted us to think that it's unlikely the normal sucralose consumption could have any effect. However, we hope that we can exploit this discovery to design new therapeutical strategies and we think that high doses of sucralose could potentially be useful into some dependent autoimmune disease. Maybe by adding sucralose to existing treatment, we can achieve a better therapeutical effect.