The gut microbiota comprises the billions of bacteria and other microbes that live in the gut. Photo credit: Alpha Tauri 3D Graphics / Shutterstock.com
During pregnancy in mice, billions of bacteria and other microbes that live in a mother's gut regulate important metabolites, small molecules that are important for healthy fetal brain development, UCLA biologists report in Nature on Sept. 23.
While the maternal gut microbiota has been linked to abnormalities in brain function and offspring behavior – often in response to factors such as infection, a high-fat diet, or stress during pregnancy – scientists had not previously known whether they affected brain development during critical events affect prenatal periods and in the absence of such environmental problems.
To test the effects of gut microbes on the metabolites and other biochemicals that circulate in the maternal blood and nourish the rapidly developing fetal brain, researchers bred mice that were treated with antibiotics to kill gut bacteria, as well as mice bred with microbes were. free in a laboratory.
"Maternal gut microbiota depletion by either method similarly disrupted fetal brain development," said lead study author Helen Vuong, a postdoctoral fellow in UCLA's Elaine Hsiao lab.
Depletion of the maternal gut microbiota changed which genes were activated in the brain of developing offspring, including many genes that are involved in creating new axons in neurons, Vuong said. Axons are tiny fibers that connect brain cells and enable them to communicate.
In particular, axons that connect the thalamus of the brain to its cortex were reduced in number and length, the researchers found.
"These axons are particularly important for the ability to understand the environment," said Vuong. "In accordance with this, the offspring of mothers without gut microbiota had impairments, particularly in sensory behavior."
The results show that the mother's gut microbiota can promote healthy fetal brain development by regulating metabolites that make their way into the fetal brain itself, Vuong said.
"When we measured the types and levels of molecules in maternal blood, fetal blood and fetal brain, we found that certain metabolites are often decreased or absent when the mother lacks an intestinal microbiota during pregnancy," she said.
The biologists then grew neurons in the presence of these key metabolites. They also introduced these metabolites into the microbiata-depleted pregnant mice.
"When we grew neurons in the presence of these metabolites, they developed longer axons and increased numbers of axons," said Vuong. "And when we supplemented the pregnant mice with key metabolites that were decreased or absent when the microbiata was depleted, the levels of these metabolites in the fetal brain were restored and the impairment of axon development and offspring behavior prevented.
"The gut microbiota has the incredible ability to regulate many biochemicals not only in the pregnant mother but also in the developing fetus and the fetal brain," said Vuong. "Our results also reveal selected metabolites that promote axon growth."
The results suggest that microbiota-nervous system interactions begin prenatally through the influence of the maternal gut microbiota on the fetal brain, at least in mice.
The applicability of the results to humans is still unclear, said lead author of the study, Elaine Hsiao, professor of integrative biology and physiology at UCLA and of microbiology, immunology and molecular genetics at UCLA College.
"We don't know if and how the results might apply to humans," said Hsiao, who is also an adjunct professor of digestive diseases at UCLA's David Geffen School of Medicine. "However, there are many neurodevelopmental disorders believed to be caused by both genetic and environmental risk factors during pregnancy. Our study suggests that maternal gut microbiota during pregnancy should also be considered a factor and should be further investigated which could possibly affect not only the health of the mother but also the health of the developing offspring. "
Hsiao, Vuong, and colleagues reported in 2019 that serotonin and drugs that target serotonin, such as antidepressants, can have a huge impact on the gut microbiota. In 2018, Hsiao and her team established a causal link between seizure susceptibility and gut microbiota and identified specific gut bacteria that play an essential role in the anti-seizure effects of the ketogenic diet.
Gut bacteria play a key role in the anti-seizure effects of the ketogenic diet
Helen E. Vuong et al., The Maternal Microbiome Modulates Fetal Neurodevelopment in Mice, Nature (2020). DOI: 10.1038 / s41586-020-2745-3
University of California, Los Angeles
Guts and Brains: How Microbes in a Mother's Gut Affect Fetal Neurodevelopment (2020, Sep 23)
accessed on September 23, 2020
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