“At first, these latest results look worrying, but there are several factors that need to be kept in mind when interpreting this study.

Firstly, mice are not mini humans. They have different biochemistries and respond differently to humans to many chemicals. For example, chocolate is harmless to humans but very toxic to mice, and the artificial sweetener aspartame can increase insulin levels in mice but not in humans. In short, while animal experiments can give you an idea about what might happen, they don’t provide definitive answers.   

In this case, the results are further complicated by the fact that the type of mouse they used (the C57BL/6J strain) is known to be susceptible to diet-induced obesity and type 2 diabetes. This means it is likely that one will see a response to glucose tolerance in these mice with almost any diet intervention, not just sweeteners. The authors also don’t seem to have measured how much of the sweeter-dosed water the mice drank, or the final concentration of sweetener in their blood, so it is unknown what amount of sweetener the mice were actually exposed to.

Sweeteners are frequently in the crosshairs of some quite sensational headlines, despite decades of research showing their safety. Even if sucralose and stevia did cause some increase in risk (which this study does not prove), that risk would likely be very small compared to proven risk factors like high-fat/high-sugar diets and lack of exercise.  

In short, while the work is interesting, I don’t think this study itself gives us more reason to worry about sweeteners. I certainly won’t be giving up my Pepsi Max just yet.”

"Most of us reach for 'diet' or 'sugar-free' options thinking we’re making the healthy choice for ourselves and our families. However, this research is a real eye-opener because it suggests that these common sweeteners - specifically sucralose and stevia, might leave a lasting mark that spans generations.

By studying mice in a controlled setting, the researchers discovered that when parents consume these sweeteners, it doesn’t just affect them. It actually changes the gut health and the 'genetic wiring' of their children and even their grandchildren, potentially making them more sensitive to metabolic issues later in life. They also show that the impact of these sweeteners isn't one-size-fits-all; instead, the effects on offspring across generations vary depending on both the specific sweetener used and their genetic sex.

It is important to note that while mice share many biological similarities with humans, we cannot directly apply these results to people just yet. However, this study adds weight to recent global health warnings suggesting we should be more cautious.

For the average Australian, the takeaway isn't that you need to clear out your pantry in a panic. Instead, it’s a reminder that 'zero calories' doesn't mean 'zero impact.' These additives are complex, and they appear to influence our biology in ways we are only just beginning to map out. We need to keep studying this to ensure that the products we use to stay healthy today aren't creating unexpected hurdles for our children tomorrow."

"My first comment would be these are mice studies and potentially might not apply at all in humans. One of their key observations of change in microbiome and lower butyrate are not seen in most human studies using normal sweetener doses, so there is a striking inconsistency with mice studies. The fact that it appears also in the F1 [first generation] and F2 [second generation] is interesting but essentially irrelevant given the human results. The power of the stdy is also low very given that only six animals in each group had  the microbiome measured.

Many variables were measured in this study with no adjustment for multiple statistical tests, so some positive results may be falsely positive. If a change in gene expression in F1 and F2 are driven by butyrate then again this would not be seen in humans. Changes in srebp1 and TLR4 may be helpful rather than negative, so no conclusions about these can be made. Moreover, the conclusion that sucralose affect glucose tolerance is not true in F0 with very mild changes in males in F1 and F2."

"This intergenerational mouse study asks an important question: Can something as common as an artificial sweetener consumed by parents leave a lasting imprint on offspring who were never directly exposed?

The answer, at least in these mice, appears to be yes. Disrupted gut bacterial communities in the parental generation were passed to pups, accompanied by lower levels of short-chain fatty acids, molecules that help regulate inflammation, immune function, and metabolism. These reductions persisted into the grandchild generation. 

Particularly interesting is that different sweeteners, sucralose and stevia, did not behave the same way. Sucralose caused broader and more lasting changes, affecting core bacterial communities, increasing intestinal inflammatory markers in the parental and first offspring generations, and suppressing a key liver metabolic gene across all three generations. Stevia's effects on gene expression were milder and mostly resolved by the second unexposed generation, though reductions in short-chain fatty acids persisted. This distinction matters, and non-nutritive sweeteners should not be treated as a single category.

There are important limitations to consider. This is a mouse study conducted under controlled laboratory conditions, very different from the complex dietary landscape of humans. The study design cannot separate maternal from paternal contributions, since both parents consumed the sweeteners. Sample sizes for the microbiome analysis were small, which warrants caution when interpreting overall findings.

Most importantly, the study demonstrates associations, not causation. Experiments using germ-free mice, faecal transplants, or cross-fostering designs would be needed to prove that the altered microbiota is actually driving the downstream metabolic and inflammatory effects.

That said, the broader possible implications are important. From a reproductive health perspective, there is already growing recognition that the microbial environment inherited at birth shapes long-term metabolic and immune development. This may influence the risk of metabolic and inflammatory conditions later in life. This study suggests that such effects may extend across generations. The old saying 'you are what you eat' may need to be extended to include our children and grandchildren."

"This newest report on Non-Nutritive Sweeteners (NNS) ought to be a sobering commentary and defining moment in the long saga of the misinterpretation of nutritional biology and the failure to apply the precautionary principle to food system regulation. Decades ago, the then ANZFA, now FSANZ, was asked to approve sucralose as an NNS. As I recall as a Board Member at the time, it was rejected on inadequate evidence and as a chlorinated molecule of sucrose, compounds themselves considered risky.

Nonetheless, repeated applications ultimately succeeded in its approval. Yet, the alleged benefit of weight management in lieu of sucrose was equivocal at best. With time, various studies reported that it was prone to cause genetic change and potentially adverse effects on the gut microbiome. The present study in mice integrates this biology to indicate not only effects on epigenetics, metabolomics which are adverse, but that they are also intergenerational.

To a lesser extent, this also applies to the so-called 'natural' NNS Stevia. The findings such as those with SCFA (short chain fatty acids) have implications for wider biology including inflammation (reported) and immune function. All the while, the very basis of NNS usage was to separate the effects of sweetness from energy metabolism (calories) as though taste receptors only mattered in the mouth. Not so!

They occur throughout the body including the nervous and reproductive systems. Unless we apply our advanced understanding of nourishment science to food system regulation and policy, our health and the planet will suffer inexorably. We can achieve acceptable sweetness by way of a plant-based biodiverse diet."

"This is a well-controlled animal study exploring how artificial sweeteners may affect not just those who consume them, but the next two generations. Male and female mice were given water supplemented with either stevia or sucralose before mating, and females continued throughout pregnancy and lactation. The authors then studied outcomes in the parents (F0), their offspring (F1), and grandchildren (F2), who had no direct exposure to the sweeteners. 

While some differences in blood glucose levels are observed, these were subtle and levels remained within expected ranges for mice. The reported changes in the gut microbiota and inflammatory gene expression, particularly in the F1 generation, underscore the need for further investigation. I agree with the authors in that these findings suggest an increased vulnerability to metabolic conditions, such as type 2 diabetes, particularly if offspring are later exposed to a Western diet and/or sedentary lifestyle. 

An important limitation is that both parents consumed the same sweetener in this study, so it is not possible to distinguish between maternal and paternal contributions. Any observed effect could arise from changes to gametes, including epigenetic effects, that are passed down to offspring. Additionally, there is some evidence in humans for an association between artificial sweetener use and gestational diabetes risk. This was not examined in the present study, but is itself known to influence offspring growth and development. 

Overall, the findings absolutely raise important questions, but their relevance to human health is yet to be determined."

"This study is interesting because it goes beyond the usual question of whether sweeteners affect metabolism in those exposed to them, and asks whether parental exposure might leave detectable changes in offspring.

In mice, parental consumption of sweeteners was associated with some changes in offspring and grand-offspring gut microbiota, faecal short-chain fatty acids, and a small number of intestinal and liver gene-expression markers, with sucralose generally showing broader effects than stevia.

That said, in this animal study, the glucose findings in the offspring were fairly modest and mixed, rather than showing a definitive pattern of metabolic impairment, so this was not a clear diabetes-like picture.

Also, the offspring findings cannot be attributed specifically to inherited biological effects, because the design does not separate gestational and lactational exposure, maternal and paternal contributions, maternal microbiome transfer, or possible litter effects. So the paper suggests an offspring effect in mice, but it does not prove that the effect was passed down biologically.

For Australians, the sensible interpretation is cautious interest rather than alarm. This animal study raises questions worth following up, but it does not justify changing consumer behaviour, clinical advice, or policy on the basis of this evidence alone."

"This is an interesting mouse study because it suggests some artificial sweeteners may have consequences beyond the individual consuming them. The authors found that parental exposure, especially to sucralose, was associated with changes in the gut microbiome, lower levels of short-chain fatty acids in faeces, and altered expression of genes linked to inflammation and metabolism, with some of these effects still detectable in children, and the following generation. This matters because gut microbes and their metabolic products are an important part of how diet influences host health.

That said, this study should be interpreted carefully. It was done in mice, not humans, and the strongest findings were in microbial and molecular markers rather than large metabolic effects. The microbiome work was also based on a relatively small number of animals, so this is better viewed as an early mechanistic study, requiring further validation, rather than a reason for alarm.

The main takeaway here is that sweeteners marketed as harmless substitutes may still have biologically meaningful effects in the gut, and we need better human studies before drawing strong conclusions about long-term health risks."

“In this study, after weaning (commencing at 4 weeks – equivalent to 6 months of age in humans), 47 male and female mice were fed either water, or the non-nutritive sweeteners (NNS) sucralose (artificial) or 'stevia' (natural) in amounts equivalent to their respective Acceptable Daily Intakes (ADIs) for 2 additional generations.

There was an alteration in glucose metabolism in second-generation male mice fed sucralose. Changes to the microbiome were observed for mice fed both NNS, and there were also lower faecal short-chain fatty acid concentrations, attributed to changes in the microbiome. There were also some changes in gene expression related to metabolism and inflammation.

It is known that 80-85% of sucralose is excreted unchanged in the faeces. 'Stevia' (Steviol glycosides) are hydrolysed to steviol in the caecum [a pouch that forms the first part of the large intestine] and are excreted in the urine (predominantly) and faeces. It is therefore unsurprising that there were some changes in faecal microbiota (in particular for sucralose) and short-chain fatty acid concentrations in the mice.

Of course, in real life, human infants are not weaned onto ADI amounts of either NNS at 6 months of age, nor do they consume it for the rest of their lives and/or until they reproduce.

Based on the most recent available survey data, Australians aged 12+ years consume 3% of the ADI for sucralose (95% consume less than 16% of the ADI) and for Australians aged 2+ years, 10-20% of the ADI for stevia (90% consume less than 20-40% of the ADI).

The research will likely be noted by Food Standards Australia New Zealand, but won’t affect current permissions within the Food Standards Code.

The results of this new research on mice have little relevance to the average Australian’s health. Consumers of non-nutritive sweeteners do not need to be alarmed.”