Maternal aspartame exposure alters lung Th1/Th2 cytokine balance in offspring through nuclear factor-κB activation

• Published in: International immunopharmacology 2025-01, Vol.145, p.113800, Article 113800
• Main Authors: Chuang, Hsiao-Chi, Yang, Yu-Chen S.H., Chou, Hsiu-Chu, Chen, Chung-Ming
• Format: Article
• Language: English
• Subjects: Animals; Aspartame; Asthma; Asthma - chemically induced; Asthma - immunology; Cytokines - metabolism; Female; Gastrointestinal Microbiome - drug effects; Gastrointestinal Microbiome - immunology; Immunoglobulin E - blood; Immunoglobulin E - immunology; Lung - drug effects; Lung - immunology; Male; Maternal Exposure - adverse effects; Mice; Mice, Inbred BALB C; NF-kappa B - metabolism; Nuclear factor-κB; Pregnancy; Prenatal Exposure Delayed Effects - immunology; T-helper cells; Th1; Th1 Cells - drug effects; Th1 Cells - immunology; Th1-Th2 Balance - drug effects; Th17; Th2; Th2 Cells - drug effects; Th2 Cells - immunology
• ISSN: 1567-5769; 1878-1705; 1878-1705
• DOI: 10.1016/j.intimp.2024.113800

[Display omitted] •Maternal intake of artificially sweetened soft drinks increased asthma risk in early childhood.•Maternal aspartame exposure regulates lung Th1/Th2 cytokine via NF-κB activation in offspring.•Aspartame acts as a sensitizing agent that contributes to the development of asthma in offspring. Epidemiological evidence suggests that maternal intake of nonnutritive sweeteners is positively associated with early childhood asthma incidence. We investigated the effects of maternal aspartame exposure during pregnancy and lactation on lung Th1/Th2 cytokine balance and intestinal microbiota in offspring and explored the mechanisms that mediate these effects. Pregnant BALB/c mice were randomly divided on gestational day 7 into two dietary intervention groups: control (drinking water only) and aspartame (drinking water +0.25 g/L aspartame) groups. The dams nursed their offspring for 3 weeks. On postnatal day 21, heart blood samples were collected, and immunoglobulin E levels were measured. Microorganisms from the lower gastrointestinal tract were sampled using a culture-independent approach. Lung tissues were harvested for biochemical analyses. Maternal aspartame exposure increased the body weight of the dams from gestational day 7 to postnatal day 21 and the body weight of the offspring from birth to postnatal day 21. Maternal aspartame exposure significantly increased the levels of Th2 cytokines (interleukin [IL]-4, IL-5, and IL-13) and IL-17 and immunoglobulin E but reduced that of a Th1 cytokine (interferon-γ) in the offspring’s lung tissues. The altered Th1/Th2 balance was accompanied by increased lung nuclear factor-κB activation. The bacterial composition and alpha-diversity of the gut microbiota of the offspring did not differ significantly between the control and aspartame groups. Our findings suggest maternal aspartame exposure influences lung Th1/Th2 cytokine balance in offspring through nuclear factor-κB activation.