A new rat study shows that sweeteners consumed by parents can reshape gut bacteria, microbial metabolites and metabolic signals in offspring, with sucralose leaving the strongest multi-generational imprint.
Study: Artificial and natural non-nutritive sweeteners drive different gut and genetic responses between generations. Image credit: Andrey Zastrozhnov/Shutterstock
In a recent study published in the journal leader in nutritionResearchers showed that non-nutritive sweeteners (NNS) eliciting different genetic and gut responses across generations.
High-sugar diets promote obesity, hyperinsulinemia, and impaired glucose tolerance, and are associated with higher risk of noncommunicable diseases in children and adults. NNSSuch as aspartame, saccharin, acesulfame K, stevia, sucralose and cyclamate, are widely used as non-caloric sugar substitutes. NNS Consumption has increased significantly across all age groups, including women of childbearing age.
According to a survey in the United States (We), used by more than 140 million adults NNS In 2020. Furthermore, recently the World Health Organization (Who) Guidelines suggest that long-term NNS Use may be associated with adverse effects, such as increased risk of heart disease and diabetes. Despite being widespread NNS Use by women of childbearing age, impact of parental intake NNS Studies are conducted on children.
Parental NNS Mouse Study Design
In the current study, researchers evaluated how parental consumption of stevia or sucralose affects fecal microbiota (FM) and short-chain fatty acids (SCFA) production, gene expression of the liver and intestines, and whether any changes are transmitted to offspring. First, four-week-old male and female mice (parental, or F0, generation) were randomized to receive water (control) or water supplemented with stevia or sucralose for 16 weeks.
Mice of the same group were crossed out at week 6. Four weeks after lactation, the first (F1) generation was weaned and followed until 20 weeks of age. Unrelated F1 mice from the same group were crossed to generate the second (F2) generation. F1 and F2 animals received only standard chow and pure water, without direct NNS exposure. Changes in food and water intake and body weight were monitored every week.
At week 20, mice of all generations were euthanized, and liver and ileal tissues were harvested. Before euthanasia, an oral glucose tolerance test (OGTT) was performed. In addition, stool samples were obtained from each generation and group before euthanasia. FM The structure was evaluated using 16S ribosomal ribonucleic acid (rRNA) Gene sequencing. SCFA Quantitation was determined using gas chromatography.
Total ribonucleic acid (royal army) were extracted from intestinal and liver tissues to determine the expression of genes involved in inflammation (tumor necrosis factor (TNF) and toll-like receptor 4 (TLR4)), intestinal barrier function (tight junction protein 1 (TJP1)), and metabolism (sterol-regulatory element-binding protein 1 (SREBP1)). The Kruskal–Wallis test and post hoc Dunn test were used to compare inter-generational and inter-group differences.
Stevia and Sucralose Glycemic Conclusion
OGTT The test revealed no difference in glucose levels between the control and sucralose groups in F0 rats. Nevertheless, men in the stevia group showed lower glucose levels at 120 minutes compared to the sucralose and control groups. Male F1 rats in the sucralose group had lower glucose levels than the stevia and control groups, although glycemic changes were overall modest and selective. Fasting glycemia was higher in F2 women in the stevia group.
In contrast, F2 males in the sucralose group had lower glycemia than those in the stevia group and higher fasting glucose than controls. There was no intergenerational change in glycemia for the control group. NNS Consumption had no effect on intestinal Tjp1 expression in F0 animals and offspring. In contrast, sucralose was associated with elevated TNF and TLR4 expression in the intestine and reduced hepatic SREBP1 expression in F0 mice relative to controls.
Experimental design for intergenerational exposure to sucralose and stevia. At 4 weeks of age, non-consanguineous, primiparous female and male C57BL/6J mice (parental (F0) generation) were randomly distributed into three groups to receive water alone (control) or water supplemented with sucralose (0.1 mg/mL) or stevia (0.1 mg/mL) for 16 weeks. To assess the intergenerational effect of non-nutritive sweeteners (NNS), F0 mice belonging to the same treatment group were mated at 10 weeks of age. After 4 weeks of lactation, the F1 offspring were weaned and followed until 20 weeks of age. The F1 and F2 generations did not receive direct NNS exposure. All mice were maintained under identical housing and rearing conditions, including the same animal room, cage type and bedding, chow batch, water source and bottle cleaning protocols, and standardized cage cleaning schedules.
Gut microbiota and SCFAs change across generations
In F1 animals, intestinal TNF and TLR4 were highly expressed. NNS groups relative to controls, and these changes were normalized to F2 mice. In F0 animals, alpha diversity did not differ between groups, but the Shannon index was higher in the stevia group compared to the sucralose and control groups. Beta diversity demonstrated significant differences among groups.
In F1 rats, the sucralose group had more observed species than the control; Shannon index was higher NNS groups compared to controls, and beta diversity differed across groups. In F2 animals, the sucralose group had more observed species and a higher Shannon index than the stevia and control groups; The beta-diversity gap persisted in this generation. The control group showed no inter-generational differences in alpha or beta diversity.
Ahead, NNS There was a significant change in it due to consumption FM Composition in F0 and F1 animals, especially in the sucralose group. Other than this, NNS-related changes FM The structure was transmitted in the F1 generation but partially restored in the F2 generation. In the F0 generation, NNS The groups showed lower fecal valerate and acetate levels than controls, with no difference in butyrate and propionate levels or. SCFA Ratio.
In F0 generation, total SCFA level was low NNS group compared to the control. In F1 animals, acetate, butyrate, valerate, and propionate levels were significantly reduced in the sucralose group. In F2 rats, the sucralose group had lower levels of propionate and acetate, and the stevia group had lower levels of valerate, butyrate, acetate, and propionate compared with controls. Total SCFA level was low NNS Group.
Transgenerational health implications of NNS exposure
together, parents NNS Consumption induced inter-generational changes in gut microbiota composition, microbial metabolite production, host glycemic responses, and hepatic and intestinal gene expression in the offspring. These findings challenge that notion NNS are metabolically inert and highlight their potential to impact the health of the offspring. Overall, sucralose showed a stronger and more persistent transgenerational signal, whereas stevia-related effects were more prominent in F1, and many of the changes were mitigated by F2. Further research is needed to delineate the underlying mechanisms and relevance to human health.
