Abstract
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 × 109 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.
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Data availability
The data support the fndings of this research are available from the corresponding author (fatih.kar@ksbu.edu.tr) upon reasonable request. The authors will take the responsibility for maintaining availability.
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This study was supported by Eskişehir Osmangazi University Scientific Research Projects Commission. (Project No: 2019–1915).
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F.K. designed, performed, analyzed all the experiments, and wrote the manuscript. C.H. and E.K. assisted in in vivo experiments, ELISA measurements, real-time qPCR and Western Blot methods. D.B.D. helped with the development of histopathological protocol. F.K. and E.K. analyzed behavioral data from maternal behavior. F.K and C.H. performed ELISA analyses to detect calprotectin levels in feces. S.U. and G.K. supervised the design, development, and analyses of molecular experiments. F.K., C.H., and G.K supervised the whole study design, development, and data analyses. F.K. and E.K. also contributed to the fnal version of the paper. All authors made manuscript revisions and approved the submitted version.
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The study was applied to the protocol approved by the ESOGU Animal Experiments Local Ethics Committee (HADYEK) with the decision number 636–1 dated 10.10.2019.
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Kar, F., Hacioglu, C., Kar, E. et al. Probiotics ameliorates LPS induced neuroinflammation injury on Aβ 1–42, APP, γ-β secretase and BDNF levels in maternal gut microbiota and fetal neurodevelopment processes. Metab Brain Dis 37, 1387–1399 (2022). https://doi.org/10.1007/s11011-022-00964-z
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DOI: https://doi.org/10.1007/s11011-022-00964-z