There has been an enormous increase in the consumption of non-nutritive sweeteners (NNS) over the last two decades correlating with increased awareness of the harms of sugar on a range of chronic health conditions. The consumption of ultra-processed foods has also been increasing and as a result, exposure to food additives such as NNS has followed the same upward trend.

Foods labelled ‘sugar-free’ or ‘low sugar’ may appeal to consumers as being a healthier alternative to foods containing added sugar, and are often given this label through the use of NNS. Foods that you may expect to contain these sweeteners include sugar-free drinks and sweets, but they are also found in other foods where you may not expect sweeteners to appear, such as in yoghurt and muesli bars.

In most countries, food authorities conduct rigorous testing of all food additives, including sweeteners, before they are approved for use. For example, in the USA, the Acceptable Daily Intake of sweeteners is based on studies in animals and is set at a level 100 times less than where no harmful effects are found. However, as research into the gut microbiota is relatively new in nutrition science, food safety testing has not previously considered the effect of sweeteners on the gut.

Research to date is mixed about the health effects of NNS. Some studies have reported an improvement in metabolic markers (such as blood sugar levels) by swapping sugar sweetened products with NNS, but other studies report neither a positive nor negative effect.

Some studies have suggested a link between higher body mass index (BMI) and increased cardiovascular disease risk with NNS consumption, however research so far is mostly observational, meaning we cannot say that one causes the other, and it may be related to other foods or drinks in the diet.

A recent experimental study published in Cell examined the effect of four NNS on 120 healthy adults. Over 14 days, participants were given doses of either saccharin, sucralose, aspartame, or stevia sachets, which were compared with control doses of glucose or no supplement. Participants had their gut microbiota and blood sugar levels monitored throughout the study including for 7 days after the intervention period.

The study found that both saccharin and sucralose significantly increased blood sugar levels over the study period compared with glucose and no-sweetener controls. In contrast, neither aspartame nor stevia had a significant effect on glucose tolerance during the two experimental weeks, or during follow-up.

There were changes in oral and gut microbiome composition and potential function after the doses of NNS. Importantly, there were no alterations to microbiome composition or function in the two control conditions (i.e., glucose or no supplement) supporting the notion that the changes observed in this study were due to the NNS sweeteners. Each NNS resulted in different changes to these microbiomes when compared to each other, and these changes could be linked to the changes in people’s glycaemic response that were observed in the NNS groups.

There were also some individualised microbial features that were able to predict glycaemic response, suggesting that how one responds to the NNS may differ from person to person as we each have a unique microbiome composition.

Interestingly, when samples from the microbiome of those that experienced the greatest glycaemic response from the NNS were transferred into germ-free mice (born without their own microbiome), these mice developed glycaemic responses like those of their human donors. This finding, also demonstrated in a previous study, may suggest a causal role between intakes of NNS and the gut microbiome in conferring metabolic changes.

Despite their low or non-caloric intake, this study reinforces the need for future investigation of the influence of NNS on metabolic and microbial health.

The findings about sucralose and saccharin altering the gut microbiome are probably unsurprising, given that neither of these sweeteners are absorbed earlier in the gastrointestinal tract, but rather make their way to the large intestine where the gut microbiome lives. On the other hand, most glucose is absorbed earlier in the gastrointestinal tract and only a small amount reaches the gut microbiome. Sugar may still influence the gut microbiome, but the pathways through which this happens and effects on human health are still not fully understood. In this study, only a small amount of sucralose and saccharin were administered (only about 1 teaspoon daily), therefore the amount may not have been large enough to have seen an effect on the gut microbiome.

It is important to note that these findings do not suggest that NNS should be replaced with sugar, as there are clear benefits to reducing added sugar for weight management, blood sugar control, and dental health. While this study shows alterations to the gut and oral microbiome following exposure to NNS, we still do not yet know the clinical significance of this on health and many more studies are needed before we can fully understand this.

Many foods and drinks containing NNS are considered to be ultra-processed foods, which our previous research has shown is linked to negative health outcomes including poorer mental health. When it comes to fluids, water is always the best choice, and if you need more flavour, you can add in fruit or herbs (such as mint or rosemary), or a bit of lemon juice. If you need a sweetness kick through other foods, fresh and dried fruit are other alternatives to foods containing added sugar or NNS.