Non-nutritive sweeteners (NNS) have become an integral component of the modern American diet due to their low caloric content and intense sweet taste. NNS such as sucralose primarily remain in the digestive tract and thus interact with the intestinal microbiota. Consumption of NNS has been linked to gut dysbiosis, contributing to activation of proinflammatory pathways and metabolic disruption. Similarly, alcohol consumption is a known modulator of the gut microbiome and can independently promote dysbiosis, gut permeability, systemic inflammation, and oxidative stress. Despite the common co-consumption of NNS with alcoholic beverages, their combined effects on gut health are poorly characterized. Therefore, this study investigated the individual and combined impact of moderate NNS and ethanol consumption on the murine gut microbiome to further understand their contribution to systemic health outcomes. Six-week-old, female C57BL6 mice were randomly assigned to one of six groups: Water, Sugar, Sucralose, Ethanol, Sugar/Ethanol, or Sucralose/Ethanol. Sweeteners were suspended in water or 10% EtOH at a concentration that aligned with the human average daily intake level of 0.1 g/L for sucralose and 100 g/L for sucrose. Treatments were provided ad libitum for 12 weeks. Gut microbiome composition was analyzed via 16S rRNA sequencing, and functional potential was inferred using PICRUSt. Serum was collected and intestinal tissue sections were processed for histological analysis. Serum analysis revealed a significant increase in blood urea nitrogen in Sucralose/Ethanol treated groups compared to Sugar/Ethanol treated groups. Sequencing data revealed shifts in microbial communities at the phylum and genus level across all treatment groups. However, alpha diversity was only significantly different in Sugar and Water groups, indicating that the sweetener and ethanol treatments affected specific taxon abundance rather than overall diversity. Further analysis of microbiota composition and functionality, and intestinal tissue imaging is forthcoming. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
Miko et al. (Fri,) studied this question.