Maternal gut bacteria associated with altered fetal brain metabolism

In a recently published study, Molecular MetabolismThe researchers: Bifidobacterium breveEffect of the presence of in the maternal gut during pregnancy on fetal brain metabolism.

study: Maternal gut Bifidobacterium breve alters fetal brain metabolism in germ-free miceImage credit: Prostock-studio/Shutterstock.com

background

Fetal growth restriction (FGR) is a serious condition in which the fetus cannot develop properly due to placental insufficiency during pregnancy. FGR can lead to postnatal neurodevelopmental disorders, including motor and cognitive impairment, learning disabilities, and cerebral palsy.

Pharmacological therapies such as aspirin, heparin, and sildenafil citrate have inconsistent effects on pregnancy outcomes, so effective treatments are needed to avoid or reduce the side effects of FGR.

Intestine Microbiome Probiotics may influence brain function and behavior, and targeting the maternal gut microbiota with probiotics may specifically alter brain development throughout the perinatal period.

Researchers previously demonstrated that three doses of Bifidobacterium breve administered to pregnant and non-pregnant germ-free mice sustained gut colonization, promoted fetal development, and altered placental structure.

About the Research

In this study, the researchers Bifidobacterium breve UCC2003 in the maternal gut coincided with changes in fetal brain growth and metabolism.

The researchers tested germ-free and germ-free pregnant mice Bifidobacterium breve UCC2003. C57BL/6J mice were administered 100 mL of the reconstituted lyophilized emulsion on days 10, 12, and 14 of gestation. B. Breve (BIF group) or control group (PBS, GF group) were orally administered.

The research team isolated fetal brain ribonucleic acid (RNA) for reverse transcription, real-time polymerase chain reaction (PCR), and measurement of the expression of cellular, metabolic, and axon formation genes.

Analyzing molecular processes B. BreveUsing samples from their previous biobank, the researchers quantified messenger RNA (mRNA) expression of key genes involved in the cell cycle, growth, microglial activity, and neurogenesis.

The researchers measured mRNA levels of transporters involved in the absorption and metabolism of branched-chain amino acids in the fetal brain and the solute carrier family 2 member 1 (Slc2a1) and Slc2a3 genes, which code for glucose transporter proteins type 1 (GLUT1) and GLUT3, in fetal brain tissue.

Brain proteins were isolated and subjected to Western blotting, and fetal brain metabolites were analyzed by nuclear magnetic resonance (NMR) spectroscopy. Fetal sex was determined by detection of the sex-determining region Y gene (SRY).

The researchers investigated signaling pathways involved in brain activity, including cell growth, proliferation, survival, nutrient absorption, dendritic structure, neuronal development and differentiation, astrogliogenesis, and cell fate transitions.

The researchers examined levels of hypoxia-inducible factor 1α (HIF-1α) and HIF-2α, as well as the abundance of pyruvate dehydrogenase kinase 1 (PDHK1), in lysates from fetal brain.

They assessed mitochondrial adenosine triphosphate (ATP) production capacity by analyzing oxidative phosphorylation (OXPHOS) complexes, using general linear and linear mixed models.

result

Maternal colonization Bifidobacterium breve It caused significant metabolic changes in the fetal brain. In particular, seven metabolites, including carnitine, citric acid, and 3-hydroxyisobutyric acid, were decreased in the fetal brain. These changes were accompanied by increased glucose transporter levels and improved absorption of branched-chain amino acids.

moreover, Bifidobacterium breve Supplementation stabilized HIF-2α and promoted the activity of metabolic pathways such as phosphatidylinositol 3 kinase-protein kinase B (PI3K-AKT), AMP-activated protein kinase (AMPK), signal transducer and activator of transcription 5 (STAT5), and Wingless-associated integration site (Wnt)-β-catenin signaling (including its receptor Frizzled-7).

The results showed that treated mouse fetuses exhibited increased dendritic branching, cell proliferation, and neuronal hypertrophy, accompanied by changes in protein stability, translation efficiency, and degradation rates.

Fetal brains from treated mice revealed reduced levels of forkhead box protein M1 (Foxm1) and cyclin-dependent kinase 1 (Cdk1) genes, downregulation of plexin A3 (Plxna3) and slit guidance ligand 1 (Slit1), and increased expression of glucose transporter and L-type amino acid transporter 1 (LAT1).

The mRNA levels of Slc37a4 and solute carrier family 16 members 1, 2, 4, and 8 were similarly higher in fetal brains of the BIF group.

Fetuses from the treated group had higher total protein content and levels of respiratory chain complex II. Levels of Achaete-scute homolog 1 (Ascl1) were also increased in the fetal brains of BIF-treated mice. Bifidobacterium breve The maternal intestine increased oxidative phosphorylation in fetal brain mitochondria.

B. Breve They produce short-chain fatty acids, which may affect the permeability of the maternal and fetal vagus nerve and blood-brain barrier. Furthermore, the release of bacterial extracellular vesicles (BEVs) affects host immunity. Altered fetal development may be related to structural and functional changes in the placental transport labyrinth region in BIF mice.

Conclusion

This study found that oral intake of probiotics by mothers Bifidobacterium breveHormonal imbalance during pregnancy has a profound effect on fetal organogenesis, affecting brain metabolism, cellular development, and axonogenesis pathways.

Bifidobacteria can improve pregnancy health and fetal development through microbiota-focused therapy.

In vitro and animal studies could elucidate mechanisms, while structural and histological analyses could determine changes in cell division, cell death, and axon development. Postnatal investigations, including behavioral studies, could assess the effects of B. breve on neurocognition.