Department of Basic Sciences, Faculty of Engineering and Natural Sciences, Kütahya Health Sciences University, Kütahya, Turkey.
Department of Medical Biochemistry, Faculty of Medicine, Duzce University, Duzce, Turkey.
Metab Brain Dis. 2022 Jun;37(5):1387-1399. doi: 10.1007/s11011-022-00964-z. Epub 2022 Mar 21.
The gut microbiota influences brain development and functioning through the gut-brain axis. This is first study regulate maternal gut microbiota and fetal neurodevelopment processes by using probiotics such as Bifidobacterium bifidum (BIF) and Lactobacillus salivarius (LAC) in the prenatal period. In this study, Wistar Albino female rats were divided into five groups; Control, lipopolysaccharide (LPS, 100 µg/kg), LPS + LAC, LPS + BIF and LPS + LAC + BIF (4 × 10 ml CFU). Maternal rats were given probiotics for 21 days. Inflammation was induced by lipopolysaccharide (LPS), on the 17th day of pregnancy. After birth, the brain tissues of the maternal and neonatal rats were removed and their blood was collected. Fecal calprotectin levels of pregnant rats were measured as an important biomarker in determining intestinal flora disruption. Calprotectin levels were high in LPS group (p < 0.05). Aβ 1-42, APP, γ secretase and β- secretase levels were higher in both maternal and neonatal LPS groups (p < 0.05). These levels were statistically decreased in the probiotic groups compared to the LPS group, as demonstrated in both biochemical and histological analyzes (p < 0.05). While BDNF mRNA expression decreased in LPS groups, APP level increased in the same group. The difference between groups in mRNA expressions in the neonatal brain tissues was similar to maternal brain tissues. What's more, BDNF/actin and APP/actin rates were proven by western blot and the damage caused by neuroinflammation in the brain tissue and the preservation of the intestinal microbiota were visualized histopathologically on the morphological structures in all groups. It will shed light on new therapeutic strategies for the impact of the use of probiotics on the neurodevelopmental processes of the neonatal against LPS-induced inflammatory responses and impaired gut microbiota in the prenatal period.
肠道微生物群通过肠-脑轴影响大脑发育和功能。这是第一项研究，即在产前使用双歧杆菌（BIF）和唾液乳杆菌（LAC）等益生菌来调节母体肠道微生物群和胎儿神经发育过程。在这项研究中，Wistar 白化雌性大鼠被分为五组：对照组、脂多糖（LPS，100μg/kg）、LPS+LAC、LPS+BIF 和 LPS+LAC+BIF（4×10mlCFU）。母体大鼠在 21 天内给予益生菌。在妊娠第 17 天，用脂多糖（LPS）诱导炎症。分娩后，取出母体和新生大鼠的脑组织并采集血液。测定孕鼠粪便钙卫蛋白水平作为确定肠道菌群失调的重要生物标志物。LPS 组钙卫蛋白水平较高（p<0.05）。母体和新生 LPS 组的 Aβ1-42、APP、γ 分泌酶和β 分泌酶水平均升高（p<0.05）。与 LPS 组相比，益生菌组的这些水平在生化和组织学分析中均显著降低（p<0.05）。虽然 LPS 组 BDNFmRNA 表达降低，但 APP 水平升高。新生脑组织中各组之间的 mRNA 表达差异与母体脑组织相似。更重要的是，通过 Western blot 证实了 BDNF/肌动蛋白和 APP/肌动蛋白的比率，并且通过组织病理学观察到神经炎症引起的脑组织损伤和肠道微生物群的保存。这将为在产前使用益生菌对神经发育过程的影响提供新的治疗策略，以对抗 LPS 诱导的炎症反应和受损的肠道微生物群。
