Department of Primary Child Health Care, Children's Hospital of Chongqing Medical University, Chongqing 400014, P.R. China.
Department of Pediatrics, Daping Hospital, Army Medical University, Chongqing, P.R. China.
J Microbiol Biotechnol. 2022 Jun 28;32(6):699-708. doi: 10.4014/jmb.2111.11048. Epub 2022 Apr 22.
Antibiotic exposure during pregnancy have an adversely effects on offspring behavior and development. However, its mechanism is still poorly understood. To uncover this, we added ceftriaxone sodium to the drinking water of rats during pregnancy and conducted three-chamber sociability test, open-field test, and Morris water maze test in 3- and 6-week-old offspring. The antibiotic group offspring showed lower sociability and spatial learning and memory than control. To determine the role of the gut microbiota and their metabolites in the changes in offspring behavior, fecal samples of 6-week-old offspring rats were sequenced. The composition of dominant gut microbial taxa differed between the control and antibiotic groups. KEGG pathway analysis showed that exerted its effects through the metabolic pathways including mineral absorption, protein digestion and absorption, Valine, leucine, and isoleucine biosynthesis. Correlation analysis showed that abundance was negatively correlated with the level of VEGF, and metabolites associated with -including 3-aminobutanoic acid, dacarbazine, L-leucine, 3-ketosphinganine, 1-methylnicotinamide, and N-acetyl-L-glutamate-were also significantly correlated with VEGF levels. The findings suggest that antibiotic exposure during pregnancy, specifically ceftriaxone sodium, will adversely affects the behavior of offspring rats due to the imbalance of gut microbiota, especially , via VEGF and various metabolic pathways.
孕期抗生素暴露会对后代的行为和发育产生不良影响。然而，其机制仍不清楚。为了揭示这一点，我们在孕期向大鼠饮用水中添加头孢曲松钠，并在 3 周和 6 周龄的后代中进行三箱社交性测试、旷场测试和 Morris 水迷宫测试。抗生素组后代的社交性和空间学习记忆能力低于对照组。为了确定肠道微生物群及其代谢物在后代行为变化中的作用，对 6 周龄后代大鼠的粪便样本进行了测序。控制组和抗生素组之间主要肠道微生物类群的组成不同。KEGG 途径分析表明，通过包括矿物质吸收、蛋白质消化和吸收、缬氨酸、亮氨酸和异亮氨酸生物合成在内的代谢途径发挥作用。相关性分析表明，丰度与 VEGF 水平呈负相关，与 -相关的代谢物，包括 3-氨基丁酸、达卡巴嗪、L-亮氨酸、3-酮鞘氨醇、1-甲基烟酰胺和 N-乙酰-L-谷氨酸，也与 VEGF 水平显著相关。这些发现表明，孕期抗生素暴露，特别是头孢曲松钠，会通过肠道微生物群的失衡，特别是 ，通过 VEGF 和各种代谢途径，对后代大鼠的行为产生不良影响。
