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A study published in Frontiers in Nutrition looks at sweeteners in mice and measures of gut microbiome, glucose tolerance and gene expression.
Prof Jules Griffin, Director of the Rowett Institute, University of Aberdeen, said:
“The paper by Francisca Concha Celume and colleagues describes an in-depth intergenerational mouse study of the effects of artificial and natural non-nutritive sweeteners on the offspring of parents that consumed the sweeteners. The study provides evidence that microbiome changes induced by artificial and natural non-nutritive sweeteners can occur across generations in mice, in the offspring that don’t directly consume the sweeteners. While the study raises questions for the research community about how these sweeteners may impact gut health across the generations, the current paper also needs to be interpreted carefully in terms of its relevance for human health. These results are in mice and may not be translatable to humans as mice are coprophagic and this provides an efficient way for the microbiome to spread from the parent to the child at the start of life. The researchers identify some genes and gut microbes that are altered in the offspring of mice, but they have looked at a relatively small snapshot of the total, there are conflicting results in other studies for these genes and these genes and microbes are not currently used to diagnose disease.”
Prof Gunter Kuhnle, Professor of Nutrition and Food Science, University of Reading, said:
“There is a large consensus that reducing the intake of sugar is overall a good thing and healthy. Artificial sweeteners can help reduce sugar intake by maintaining taste while reducing the calories – but there has been some controversy regarding their potential effect on health. WHO and SACN have a cautionary advice to limit the use of artificial sweeteners, although there are only limited data on adverse effects on health – mainly based on observational studies that have considerable limitations. There is also a general recommendation to reduce the overall ’sweetness’ of the diet, but several studies have shown that sweeteners do not affect preferences for sweetness.
“Sucralose and stevia are two sweeteners commonly used – and properly authorised for use – in the UK and Europe. Sucralose has only recently been reassessed by the European Food Safety Authority (EFSA) which has found no reason to make any changes to their recommendations. Stevia has also been assessed by EFSA in 2010 (and several follow-up assessments), and there have been no changes to the recommended acceptable daily intake (ADI – amount that, if consumed for a lifetime, could be expected not to have an adverse effect on health).
“While stevia and sucralose are both commonly used sweetener, they are quite different in their chemical structure and mode of action. Sucralose is a chemically modified form of normal sugar, while stevia is extracted from the South American stevia plant and is chemically fundamentally different from sugar. They both have in common that they can bind to sweet receptors, but otherwise they follow different metabolic pathways.
“The current study investigates the effect of stevia and sucralose on a wide range of risk markers in a multi-generation study in mice. With a large number of endpoints, there is always the risk of false-positives, even when authors attempt to adjust for false-discovery rates, and it is important to keep this in mind.
“The authors – and the press release – mention an impact on the oral glucose tolerance test, but unfortunately the results of this are only in the supplement and only provided as graphic and not with actual figures, making an interpretation difficult. While there might be a statistically significant difference, it is impossible to say whether the results are in any way clinically meaningful.
“It is also very difficult to interpret the data on the gut microbiome. Mice and humans differ significantly in the anatomy of their intestinal tract, and in contrast to humans, mice rely on consuming their own faeces as a normal part of their diet. This makes it different to translate these findings to humans. Moreover, it is very difficult to identify whether a change in the microbiome is beneficial or not: many nutritionists would consider a more diverse microbiome to be beneficial to health. The main reason for this is that most dietary changes – beneficial or not – will affect the gut microbiome.
“Regulatory agencies such as the UK’s Food Standards Agency (FSA) or EFSA are actively working on the question on how to interpret changes in the gut microbiome – but this is unfortunately a very complex question.
“In conclusion: the study provides interesting data for future risk assessments of artificial sweeteners, and I agree with the author in their press release that this should not cause any alarm.”
Prof Parveen Yaqoob, Professor of Nutritional Physiology, and Deputy Vice Chancellor & Pro-Vice-Chancellor (Research & Innovation), University of Reading, said:
“This is an interesting and carefully conducted animal study, but the claims around “transgenerational effects” should be interpreted with caution.
“The concept of epigenetic inheritance is highly contested (Edith Heard, the Director of the Francis Crick Institute, works on epigenetics and is particularly critical of the concept). While there is robust evidence that environmental factors (including diet) can influence gene expression, convincing evidence that such effects persist across multiple generations in mammals, particularly via nutritionally induced mechanisms, remain limited and often difficult to reproduce. In mice, what appears to be a “second-generation” effect can actually be mediated by changes in the maternal environment, early-life microbial colonisation, or behavioural factors that have nothing to do with genetic reprogramming.
“The reliance on a small number of candidate genes in this study is another limitation. Changes in expression of a handful of inflammation- or metabolism-related genes provide, at best, a narrow snapshot and are highly sensitive to context, so it is difficult to assess whether these differences are biologically meaningful or simply reflect normal variability. The modest differences in glucose tolerance described in the paper are subtle and fall short of indicating meaningful biological relevance; the authors themselves acknowledge that translation to humans should be interpreted with caution.
“Despite the limitations of the study, non-nutritive sweeteners are justifiably an active area of research, particularly with regard to their interaction with the gut microbiome (most products containing them will warn against over-consumption because of effects on the gut). Studies like this contribute to a growing body of literature suggesting that these compounds may not be metabolically inert, even if the magnitude and clinical relevance of effects in humans remain uncertain.”
Artificial and Natural Non-Nutritive Sweeteners Drive Divergent Gut and Genetic Responses Across Generations’ by Francisca Concha Celume was published in Frontiers in Nutrition at 05:00 UK time on Friday 10 April 2026.
DOI: 10.3389/fnut.2026.1694149
Declared interests
Prof Jules Griffin: “I am a consultant for Sitryx, a company specialising in designing drugs to target immunometabolism.
I have received funding from the European Union to investigate endocrine disrupting chemicals and hold a grant from UK Research and Innovation examining the health benefits of a fish diet.
I hold shares in GlaxoSmithKline and Haleon plc.”
Prof Gunter Kuhnle: “I am a former member of the UK Committee on Toxicity of Chemicals in Food, Consumer Products, and the Environment; a current member of the Advisory Committee on Novel Foods and Processes; the Director of the Chemical Analysis Facility at the University of Reading, which provides analytical services to academic and commercial clients; have received research funding (2010–20) from Mars for work on flavanols; and have received consultancy payments from RSM UK and EQT, paid to the University of Reading. As a member of the EFSA ANS panel (2018-2019) and the UK’s COT (2019-2025) I was involved in the evaluation of stevia glucosides.”
Prof Parveen Yaqoob: “No interests to declare.”