Obesogenic Effect of Sulfamethoxazole on Drosophila melanogasterwith Simultaneous Disturbances on Eclosion Rhythm, Glucolipid Metabolism, and Microbiota

Antibiotics have recently gained attention because they are emerging environmental pollutants with obesogenic properties. In this study, Drosophila melanogasterwere exposed to sulfamethoxazole (SMX), a sulfonamide antibiotic, and the effects were measured on circadian rhythm (represented by the eclosion rhythm), lipid metabolism, and microbiota. Circadian rhythm disorder was considered due to its connection with lipid metabolism and microbiota in association with obesity. SMX decreased the proportion of adult flies that eclosed in the morning (AM adults) and increased the proportion of PM adults. Moreover, SMX increased the body weight of PM adults, indicating that SMX exposure caused dysrhythmia in eclosion together with obesity. In measurements of key metabolites and metabolic enzymes, SMX exposure stimulated 3 indices in AM adults and 10 indices in PM adults. In AMP-activated protein kinase and insulin/IGF-1 signaling pathways, SMX upregulated six genes in AM adults and nine genes in PM adults. Finally, microbiota analysis demonstrated that SMX increased the Firmicutes/Bacteroides ratios (F/B) by 79.6- and 5.8-fold compared to concurrent controls in AM and PM adults. Collectively, these results suggest that SMX showed obesogenic effects accompanied with dysrhythmia and disturbances in lipid metabolism and microbiota. Further studies on the intrinsic connection are needed.