Abstract: Sucralose is currently one of the most widely used sugar substitutes. Its safety assessment is still limited at the toxic level, so it is impossible to determine the effect of sucralose on human health. In this study, potential changes in the intestinal microecology of BALB/C mice after the ingestion of sucralose were investigated as well as its impact on the diversity and composition of intestinal flora. Further, we inferred whether the intestinal microecological changes can cause damage to the immune barrier and consequently chronic diseases. In this experiment, BALB/C male mice at the age of 4 weeks were randomly divided into blank control, low-, medium- and high-dose sucralose groups (15, 25 and 50 mg/(kg mb·d), respectively). After administration for 6 weeks, blood samples were collected from the eyeballs and all mice were sacrificed to measure the structure of intestinal flora in mice (by 16S rDNA high-throughput sequencing), spleen index, thymus index, contents of the inflammatory cytokine interleukin (IL)-1β, tumor necrosis factor (TNF)-α, secretory immunoglobulin A (SIgA) and intestinal tissue pathological changes. The results showed that compared with the blank group, the intestinal flora diversity of mice was significantly reduced after ingestion of sucralose (P < 0.05). At the phylum level, the abundance of Actinomycetes and Proteobacteria increased significantly (P < 0.05). At the family level, the abundance of Clostridiaceae and Ritiaceae was significantly reduced (P < 0.05). At the level of genus, the abundance of Bacteroidetes was significantly increased (P < 0.05). The immune organ index and SIgA level in mice were significantly reduced (P < 0.05), and intestinal epithelial lesions were observed. These results showed that sucralose could lead to structural changes of intestinal flora in mice, reduced intestinal flora diversity, and an imbalance in intestinal homeostasis, thus reducing both local and systemic immune response and increasing the risk of various diseases.

Key words: sucralose; intestinal microecology; immunity; diversity; intestinal homeostasis