Maternal Aspartame Exposure Induces Neonatal Pulmonary Metabolic Dysregulation and Redox Imbalance: A Multiomics Investigation of Gut Microbiota-Host Interactions.

Redox imbalance during development may make offspring more vulnerable to long-term pulmonary issues. Maternal aspartame intake was investigated for its influence on neonatal lung redox biology. Using a multiomics approach (untargeted metabolomics, gut microbiota profiling, redox-inflammation markers), aspartame exposure (0.25 g/L in drinking water from gestational day 7 to postnatal day 21) was found to significantly alter neonatal pulmonary metabolic profiles, especially purine metabolism and the pentose phosphate pathway. MetOrigin analysis suggested a potential link between these metabolic changes and host-microbiota cometabolism. Elevated 8-hydroxy-2'-deoxyguanosine and malondialdehyde, along with decreased glutathione, suggested oxidative stress. These redox disturbances occurred with increased cleaved caspase-1 and interleukin-1β, consistent with inflammasome activation. Taken together, these integrated chemical and biological data propose a potential pathway by which early life aspartame exposures may disrupt redox-sensitive metabolic networks and inflammatory responses in the developing lung. These results emphasize the value of assessing artificial sweeteners when considering developmental redox homeostasis and immune-metabolic health.