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Effects of Varied Sulfamethazine Dosage and Exposure Durations on Offspring Mice
Hongchao Wang1,2, Danting Dang1,2, Leilei Zhu1,2
1State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi 214122, China.
Abstract:
The development of antibiotics was a turning point in the history of medicine; however, their misuse and overuse have contributed to the current global epidemic of antibiotic resistance. According to epidemiological studies, early antibiotic exposure increases the risk of immunological and metabolic disorders. This study investigated the effects of exposure to different doses of sulfamethazine (SMZ) on offspring mice and compared the effects of exposure to SMZ on offspring mice in prenatal and early postnatal periods and continuous periods. Furthermore, the effects of SMZ exposure on the gut microbiota of offspring mice were analyzed using metagenome. According to the results, continuous exposure to high-dose SMZ caused weight gain in mice. IL-6, IL-17A, and IL-10 levels in the female offspring significantly increased after high-dose SMZ exposure. In addition, there was a significant gender difference in the impact of SMZ exposure on the gut microbiota of offspring: Continuous high-dose SMZ exposure significantly decreased the relative abundance of Ligilactobacillus murinus, Limosilactobacillus reuteri, Lactobacillus johnsonii, and Bifidobacterium pseudolongum (p < 0.05) in female offspring mice; however, these significant changes were not observed in male offspring mice.
Insights
Early exposure to sulfamethazine (SMZ) in mice led to weight gain and altered immune responses, particularly in females. Continuous high-dose SMZ also significantly impacted gut microbiota composition in female offspring.
Area of Science:
- Environmental Health
- Microbiology
- Immunology
- Toxicology
Background:
- Antibiotic misuse fuels the global antibiotic resistance crisis.
- Early antibiotic exposure is linked to increased risks of immunological and metabolic disorders.
- Sulfamethazine (SMZ) is a commonly used antibiotic.
Purpose of the Study:
- To investigate the effects of different doses and exposure periods of sulfamethazine (SMZ) on offspring mice.
- To compare prenatal, early postnatal, and continuous SMZ exposure impacts.
- To analyze SMZ's effects on offspring gut microbiota composition.
Main Methods:
- Offspring mice were exposed to varying doses of sulfamethazine (SMZ) during different developmental periods.
- Body weight, immune markers (IL-6, IL-17A, IL-10), and gut microbiota were analyzed.
- Metagenomic sequencing was employed to assess gut microbial composition.
Main Results:
- Continuous high-dose SMZ exposure resulted in significant weight gain in offspring mice.
- Female offspring exposed to high-dose SMZ showed elevated levels of IL-6, IL-17A, and IL-10.
- High-dose SMZ significantly reduced beneficial bacteria (e.g., *Ligilactobacillus murinus*, *Bifidobacterium pseudolongum*) in female mice, with no significant changes observed in males.
Conclusions:
- Continuous high-dose SMZ exposure adversely affects offspring mice, causing weight gain and immune dysregulation, particularly in females.
- SMZ exposure significantly alters gut microbiota composition in a gender-specific manner, with females being more susceptible to reductions in key bacterial species.
- These findings highlight the potential long-term health consequences of early-life antibiotic exposure.

