A recent study published in Molecular Metabolism highlights the significant impact of the gut microbiome, specifically Bifidobacterium breve, on fetal brain development during pregnancy. This research sheds light on the potential of probiotics to address fetal growth restriction (FGR), a condition in which a fetus fails to reach full development due to placental insufficiency, leading to serious postnatal neurodevelopmental issues such as motor and cognitive dysfunction, learning disabilities, and even cerebral palsy.
Bifidobacterium is a genus of Gram-positive, anaerobic, and nonmotile bacteria that, like Lactobacillus, are prevalent in the gastrointestinal tract. Species of Bifidobacterium, including Bifidobacterium breve UCC2003, are recognized for their ability to beneficially modulate the gut microbiota and influence host physiological responses.
Fetal growth restriction remains a challenging condition for obstetricians, as current pharmacological therapies like aspirin, heparin, and sildenafil citrate have shown inconsistent outcomes in managing pregnancy-related complications. Given the critical role of the gut microbiome in influencing brain function and behavior, the study explores the possibility of using
The pre-clinical study has demonstrated that administering Bifidobacterium breve to pregnant and non-pregnant germ-free mice resulted in sustained gut colonization, enhanced fetal development, and structural changes in the placenta. In this study, germ-free pregnant mice were divided into two groups: one received Bifidobacterium breve UCC2003, and the other served as the control group. The researchers then conducted a detailed analysis of fetal brain tissue, isolating ribonucleic acid (RNA) for reverse transcription and real-time polymerase chain reaction (PCR) to assess gene expression related to cellular metabolism, axonogenesis, and other critical processes.
Tello and colleagues noticed that when mothers were colonized with Bifidobacterium breve, it resulted in significant metabolic changes in the fetal brain. Specifically, the levels of seven metabolites, such as carnitine and citrate, were decreased in the embryonic brain of the treated group. These changes were linked to an increase in glucose transporter levels and enhanced absorption of branched-chain amino acids. The supplementation with Bifidobacterium breve also stabilized hypoxia-inducible factor-2 alpha (HIF-2α) and activated several key metabolic pathways, including phosphatidylinositol 3-kinase-protein kinase B (PI3K-AKT), AMP-activated protein kinase (AMPK), and Wingless-related integration site (Wnt)-β-catenin signaling. These pathways are essential for cellular growth, proliferation, survival, and neuronal development.
The study further revealed increased dendritic branching, cellular proliferation, and neuronal hypertrophy in the fetuses of the treated mice. There were also alterations in protein stability, translational efficiency, and degradation rates, indicating a profound impact on brain development at the molecular level. Moreover, the expression of genes related to glucose transporters and L-type amino acid transporter 1 (LAT1) was significantly upregulated in the treated group. This was complemented by higher mRNA levels of solute carrier family 16 members 1, 2, 4, and 8, which play a crucial role in cellular metabolism.
The findings suggest that maternal Bifidobacterium breve supplementation can enhance fetal brain metabolism by promoting oxidative phosphorylation in fetal brain mitochondria. This enhancement is likely due to the short-chain fatty acids produced by Bifidobacterium breve, which influence the vagus nerve and blood-brain barrier permeability. Furthermore, the release of bacterial extracellular vesicles (BEVs) by bacteria may also play a role in modulating host immunity and contributing to the observed fetal developmental changes.
The study concludes that maternal oral consumption of probiotics, particularly Bifidobacterium breve, during pregnancy has a significant positive impact on fetal organogenesis, affecting brain metabolism, cell development, and axonogenesis pathways. This research paves the way for microbiota-focused therapies to improve gestational health and fetal development. Future studies are needed to further elucidate the underlying mechanisms of these effects. In vitro and animal models could provide more insights into the cellular and molecular changes, while postnatal behavioral studies could assess the long-term neurocognitive implications of Bifidobacterium breve supplementation during pregnancy.
References
- Lopez-Tello J, Kiu R, Schofield Z, Zhang CXW, van Sinderen D, Le Gall G, et al. Maternal gut Bifidobacterium breve modifies fetal brain metabolism in germ-free mice. Molecular Metabolism. 2024 Aug 8;102004.
- Lopez-Tello J, Schofield Z, Kiu R, Dalby MJ, van Sinderen D, Le Gall G, et al. Maternal gut microbiota Bifidobacterium promotes placental morphogenesis, nutrient transport and fetal growth in mice. Cell Mol Life Sci. 2022 Jun 28;79(7):386.
- Bifidobacterium Breve – an overview | ScienceDirect Topics [Internet]. [cited 2024 Aug 26]. Available from: https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/bifidobacterium-breve