Department of Primary Child Health Care, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.
National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China.
BMC Microbiol. 2021 Jun 3;21(1):166. doi: 10.1186/s12866-021-02231-0.
Antibiotic exposure during pregnancy will adversely affect the growth of offspring; however, this remains controversial and the mechanism is poorly understood. To study this phenomenon, we added ceftriaxone sodium to the drinking water of pregnant rats and continuously monitored the body weight of their offspring. The results showed that compared with the control group, the offspring exposed to antibiotics during pregnancy had a higher body weight up to 3 weeks old but had a lower body weight at 6 weeks old. To determine the role of the gut microbiota and its metabolites in the growth of offspring, we collected feces for sequencing and further established that the experimental group has a different composition ratio of dominant bacteria at 6 week old, among which S24-7 correlated negatively with body weight and the metabolites that correlated with body weight-related unique flora were L-Valine, L-Leucine, Glutaric acid, N-Acetyl-L-glutamate, and 5-Methylcytosine. To further explore how they affect the growth of offspring, we submitted these data to Kyoto Encyclopedia of Genes and Genomes website for relevant pathway analysis. The results showed that compared with the control, the following metabolic pathways changed significantly: Valine, leucine, and isoleucine biosynthesis; Protein digestion and absorption; and Mineral absorption. Therefore, we believe that our findings support the conclusion that ceftriaxone sodium exposure in pregnancy has a long-lasting adverse effect on the growth of offspring because of an imbalance of gut microbiota, especially S24-7, via different metabolic pathways.
孕期接触抗生素会对后代的生长发育产生不利影响,但这仍然存在争议,其机制尚不清楚。为了研究这一现象,我们在怀孕大鼠的饮用水中添加了头孢曲松钠,并持续监测其后代的体重。结果表明,与对照组相比,孕期接触抗生素的后代在 3 周龄时体重较高,但在 6 周龄时体重较低。为了确定肠道微生物群及其代谢物在后代生长中的作用,我们收集粪便进行测序,并进一步确定实验组在 6 周龄时具有不同的优势菌组成比例,其中 S24-7 与体重呈负相关,与体重相关的独特菌群相关的代谢物有 L-缬氨酸、L-亮氨酸、戊二酸、N-乙酰-L-谷氨酸和 5-甲基胞嘧啶。为了进一步探讨它们如何影响后代的生长,我们将这些数据提交给京都基因与基因组百科全书网站进行相关的途径分析。结果表明,与对照组相比,以下代谢途径发生了显著变化:缬氨酸、亮氨酸和异亮氨酸生物合成;蛋白质消化和吸收;以及矿物质吸收。因此,我们认为我们的研究结果支持头孢曲松钠暴露于孕期对后代生长有长期不良影响的结论,这是由于肠道微生物群失衡,特别是 S24-7 通过不同的代谢途径造成的。