Bifidobacterium in Maternal Gut Found to Alter Fetal Brain Growth

By Dr. Chinta SidharthanReviewed by Lily Ramsey, LLMAug 29 2024

A plethora of evidence now supports the role of various host microbiomes in human disease, metabolism, and physiology. However, the field of microbiome contributions to gestational health and their roles in fetal development remains largely unexplored.

In a recent study published in Molecular Metabolism, researchers from the United Kingdom used germ-free murine models to examine the impact of the bacteria Bifidobacterium breve's colonization of the maternal gut on key metabolites and critical cellular and metabolic pathways in the fetal brain.

​​​​​​​Study: Maternal gut Bifidobacterium breve modifies fetal brain metabolism in germ-free mice. Image Credit: morrowlight/Shutterstock.com

Background

Recent research suggests that the gut microbiome plays an important role in the regulation of most developmental processes, and dysbiosis in the gut microbiome is implicated in various diseases and disorders, including schizophrenia, Parkinson’s disease, and metabolic disorders such as type 2 diabetes.

The gut microbiome composition is believed to undergo substantial changes during pregnancy, and perturbations in the gut microbiome of pregnant women have been linked to preeclampsia, hypertensive disorder, and abnormal placental growth.

Fetal growth restriction is also linked to placental insufficiency and can impact vital processes in the fetus, including the development of key organs such as the heart, brain, and kidneys.

Suboptimal conditions in the intrauterine environment can disrupt the fetus's brain development, leading to various neurodevelopmental, cognitive, and motor dysfunctions. However, the increased abundance of Bifidobacterium breve in the maternal gut is believed to have numerous benefits for maternal and fetal health.

About the Study

In the present study, the researchers investigated whether the abundance of B. breve in the gut of pregnant germ-free mice had an impact on the metabolism and development of the fetal brain.

Their hypothesis was based on previous findings in which Bifidobacterium species were found to impact immune response modulation and protect against various infectious diseases.

Pregnant mice were administered either a dose of lyophilized, reconstituted B. breve or a dose of 4% skimmed milk reconstituted in phosphate buffer saline, which served as the vehicle control.

The treatments were administered on the 10^th gestational day, and two additional doses were administered on gestational days 12 and 14. The treatment day selections reflected the time frame in which most women take their probiotic supplements during pregnancy.

To understand the impact of B. breve treatment on the development of the fetal brain, the researchers extracted the ribonucleic acid (RNA) from three randomly selected fetal mouse brains from the treatment and control groups and reverse transcribed the RNA.

Subsequently, real-time polymerase chain reaction (PCR) was used to analyze the expression levels of two reference genes in the samples.

The reference genes were Actb, which encodes the protein β-actin, which plays an important role in cell growth and brain development, and the Gapdh gene, which encodes the enzyme glyceraldehyde-3-phosphate dehydrogenase, which is essential for glycolysis.

The brain samples were also used for protein extraction, radioimmunoprecipitation assays, and Western blot analysis to analyze the proteins.

Additionally, the metabolites from the fetal brain were extracted and analyzed using nuclear magnetic resonance spectroscopy. The primer for the sex-determining region Y gene (Sry) gene was also used to determine fetal sex.

Major Findings

The results from the murine model experiments showed that the presence of Bifidobacterium in the maternal gut during pregnancy could significantly modify the development and metabolism of the fetal brain.

The fetal brains from the B. breve treatment group showed a substantial reduction in the levels of ten metabolites.

A previous study by the same team had found no differences in the concentration of these metabolites in the labyrinth zone of the placenta or the fetal liver in association with Bifidobacterium supplementation, indicating that the presence of Bifidobacterium in the maternal gut induced distinct responses in various fetal tissues and organs.

The levels of amino acids such as leucine, alanine, and valine were found to be reduced in the fetal brains from the Bifidobacterium treatment group, indicating an increased use of these amino acids during brain development.

Additionally, 3-hydroxybutyrate, which can function as an alternate source of energy to glucose, was also found to be at lower concentrations in the fetal brains.

Citrate and carnitine, which are part of the tricarboxylic acid cycle in the mitochondria, were also found at lower concentrations in association with Bifidobacterium treatment. The fetal brains after Bifidobacterium treatment also showed an increase in the mitochondrial complex-II levels.

An increase in the uptake of glucose transporters was also observed in the fetal brains after Bifidobacterium treatment, and the expression of vital metabolic pathways was elevated.

Furthermore, the genes and proteins involved in mitochondrial function, axogenesis, and cellular growth showed various modifications, suggesting increased brain development.

Conclusions

Overall, the findings showed that supplementation of the maternal gut microbiome with Bifidobacterium during pregnancy had beneficial effects on the metabolism and growth of the fetal brain.

These results provide new potential therapeutic options for improving fetal development and gestational health.