This shows a pregnant woman.
The microbiota of the mother or dam is thought to be important for the development and health of her offspring. Credit: Neuroscience News

Mother’s Microbes Influence Fetal Brain and Gut Development

Summary: Researchers discovered the activity of genes in the fetal intestine, brain, and placenta is influenced by the microbes in the mother’s body.

In a study comparing normal mice with germ-free mice in sterile environments, significant differences were found in gene expressions associated with the immune system, nervous system, and pregnancy regulation.

The results suggest that the maternal microbiota and the compounds it produces play a pivotal role in the offspring’s development and health. Notably, many of these metabolites affected by the maternal microbiota were previously unknown.

Key Facts:

  1. The mother’s microbiota affects gene activity in the fetal intestine, brain, and placenta, pointing to its crucial role in the offspring’s development and health.
  2. Differences in gene expression were more pronounced in male fetuses, hinting they might be more sensitive to maternal microbiota impacts.
  3. The research discovered new metabolites, believed to be influenced by the maternal microbiota, that might impact fetal development, especially in the intestine and brain.

Source: University of Helsinki

In a Finnish study, significant differences in the gene activity of the fetal intestine, brain and placenta were identified, depending on the microbes in the mother’s body and the compounds produced by them. The findings indicate that maternal microbes are important to her offspring’s development and health.

The microbiota of the mother or dam is thought to be important for the development and health of her offspring. However, so far little is known about how interactions with the microbiota begin and what the mechanisms of action are.

A collaborative study carried out at the Universities of Helsinki, Eastern Finland and Turku investigated how the maternal microbiota affects fetal development by comparing the fetuses of normal and germ-free mouse dams living in a sterile environment.

The researchers measured gene expression and the concentrations of small-molecular compounds, or metabolites, in the fetal intestine, brain and placenta.

“The effects of the dam microbiota and the metabolites it produces on fetal development have not been previously investigated in such a comprehensive manner. Our study sheds light on the significance of the microbiota and the mechanisms by which the microbiota affects individual development and pregnancy.

“We identified previously unknown compounds in the fetus, which are likely to be microbial and which can be important for individual development,” says Mikael Niku, the principal investigator of the study from the Faculty of Veterinary Medicine, University of Helsinki.

The researchers demonstrated that there were considerable differences in gene expression in the intestine, brain and placenta of the fetuses of germ-free and normal mouse dams. In the gut, genes associated with the immune system and host–microbe interactions were less active in the fetuses of germ-free dams.

There were significant differences in the expression of genes in the brain associated with the development and functioning of the nervous system. In the placenta, there were differences in the expression of several important genes that regulate pregnancy.

The differences were more extensive in male fetuses, indicating that they may be more sensitive to the effects of the maternal microbiota, at least in mice.

The researchers discovered that the expression of many important genes was associated with the concentration of metabolites likely to be modulated by the maternal microbiota. These metabolites were absent in the fetuses of germ-free dams, or occurred at least at significantly lower concentrations.

“It would appear that such microbial products are likely to affect the development of the intestine and brain as well as the functioning of the placenta. Many of these metabolites are previously unknown,” Niku notes.

The group is now investigating the occurrence of microbial metabolites in other mammals: piglets and calves, as well as in the meconium and amniotic fluid samples of babies.

Today, deficiencies in the host–microbe interactions of the early stages of life caused by, for example, an unbalanced environment or antibiotics, may predispose the offspring to dysfunction in the immune system, such as inflammatory bowel diseases and allergies.

“Our research helps us understand the origin of such disorders, making it potentially possible in the future to enhance their prevention and treatment,” Niku muses.

About this neurodevelopment research news

Author: Eeva Karmitsa
Source: University of Helsinki
Contact: Eeva Karmitsa – University of Helsinki
Image: The image is credited to Neuroscience News

Original Research: Open access.
Impacts of maternal microbiota and microbial metabolites on fetal intestine, brain, and placenta” by Mikael Niku et al. BMC Biology


Abstract

Impacts of maternal microbiota and microbial metabolites on fetal intestine, brain, and placenta

Background

The maternal microbiota modulates fetal development, but the mechanisms of these earliest host-microbe interactions are unclear. To investigate the developmental impacts of maternal microbial metabolites, we compared full-term fetuses from germ-free and specific pathogen-free mouse dams by gene expression profiling and non-targeted metabolomics.

Results

In the fetal intestine, critical genes mediating host-microbe interactions, innate immunity, and epithelial barrier were differentially expressed. Interferon and inflammatory signaling genes were downregulated in the intestines and brains of the fetuses from germ-free dams.

The expression of genes related to neural system development and function, translation and RNA metabolism, and regulation of energy metabolism were significantly affected. The gene coding for the insulin-degrading enzyme (Ide) was most significantly downregulated in all tissues. In the placenta, genes coding for prolactin and other essential regulators of pregnancy were downregulated in germ-free dams. These impacts on gene expression were strongly associated with microbially modulated metabolite concentrations in the fetal tissues.

Aryl sulfates and other aryl hydrocarbon receptor ligands, the trimethylated compounds TMAO and 5-AVAB, Glu-Trp and other dipeptides, fatty acid derivatives, and the tRNA nucleobase queuine were among the compounds strongly associated with gene expression differences. A sex difference was observed in the fetal responses to maternal microbial status: more genes were differentially regulated in male fetuses than in females.

Conclusions

The maternal microbiota has a major impact on the developing fetus, with male fetuses potentially more susceptible to microbial modulation. The expression of genes important for the immune system, neurophysiology, translation, and energy metabolism are strongly affected by the maternal microbial status already before birth. These impacts are associated with microbially modulated metabolites. We identified several microbial metabolites which have not been previously observed in this context. Many of the potentially important metabolites remain to be identified.

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