Scientists in Chile aimed to compare, in mice, the effect of parental sucralose or stevia consumption on the diversity and composition of microbes in the gut as well as short-chain fatty acid (SCFA) concentrations. They also considered the expression of Tlr4, Tnf, Tjp1 and Srebp1 in the liver and intestines. These are genes and proteins that play critical and interrelated roles in regulating inflammation, metabolism, and gut barrier function. The study also aimed to determine whether these changes can be transmitted across generations.
Male and female mice were divided into three groups to receive water alone or water supplemented with sucralose or stevia for 16 weeks (F0 generation). The F0 mice were then bred to produce the F1 generation, and the F1 mice were bred to produce the F2 generation. The F1 and F2 animals did not receive non-nutritive sweeteners.
Compositional changes in the faecal microbiota were greater in the F0 and F1 generations, particularly those exposed to sucralose. Animals from the F0 Sucralose and Stevia groups had lower SCFA concentrations, and this trait was passed on to the next generations. In terms of gene expression the expression of liver Srebp1 and intestinal Tnf and Tlr4 also appear to be transmitted across generations.
The authors concluded that:
‘Our findings demonstrate that [in mice] parental consumption of sucralose or stevia induces persistent, intergenerational changes in host metabolism, intestinal and hepatic gene expression, gut microbiota composition, and microbial metabolite production in unexposed offspring. These results challenge the long-standing assumption that non-nutritive sweeteners are metabolically inert and underscore their potential to influence offspring health through microbial and molecular pathways. Given the widespread use of NNS during critical developmental periods, these findings raise important questions about their safety and long-term impact. Future research should aim to clarify the mechanisms underlying these intergenerational effects, their reversibility, and relevance to human health. A deeper understanding of how NNS shape host–microbiota interactions across generations is essential for developing evidence-based dietary guidelines and informing public health policies.’
Concha Celume F, Pérez-Bravo F, Magne F, Olivares R and Gotteland M (2026) Artificial and natural non-nutritive sweeteners drive divergent gut and genetic responses across generations. Frontiers in Nutrition, 13:1694149.
doi: 10.3389/fnut.2026.1694149
