How microbes in a mother's intestines affect fetal neurodevelopment


Date:
September 23, 2020
Source:
University of California - Los Angeles
Summary:
During pregnancy in mice, the billions of bacteria and other
microbes that live in a mother's intestines regulate key
metabolites, small molecules that are important for healthy fetal
brain development, biologists report. Scientists had not known
until now whether the maternal gut microbiota influenced brain
development during critical prenatal periods.



FULL STORY ========================================================================== During pregnancy in mice, the billions of bacteria and other microbes that
live in a mother's intestines regulate key metabolites, small molecules
that are important for healthy fetal brain development, UCLA biologists
report Sept. 23 in the journal Nature.


========================================================================== While the maternal gut microbiota has been associated with abnormalities
in the brain function and behavior of offspring -- often in response to
factors like infection, a high-fat diet or stress during pregnancy -- scientists had not known until now whether it influenced brain development during critical prenatal periods and in the absence of such environmental challenges.

To test the impact the gut microbiata has on the metabolites and other biochemicals that circulate in maternal blood and nurture the rapidly developing fetal brain, the researchers raised mice that were treated
with antibiotics to kill gut bacteria, as well as mice that were bred microbe-free in a laboratory.

"Depleting the maternal gut microbiota, using both methods, similarly
disrupted fetal brain development," said the study's lead author, Helen
Vuong, a postdoctoral scholar in laboratory of UCLA's Elaine Hsiao.

Depleting the maternal gut microbiota altered which genes were turned
on in the brains of developing offspring, including many genes involved
in forming new axons within neurons, Vuong said. Axons are tiny fibers
that link brain cells and enable them to communicate.

In particular, axons that connect the brain's thalamus to its cortex
were reduced in number and in length, the researchers found.



========================================================================== "These axons are particularly important for the ability to sense the environment," Vuong said. "Consistent with this, offspring from mothers
lacking a gut microbiota had impairments in particular sensory behaviors."
The findings indicate that the maternal gut microbiota can promote
healthy fetal brain development by regulating metabolites that enter
the fetal brain itself, Vuong said.

"When we measured the types and levels of molecules in the maternal blood, fetal blood and fetal brain, we found that particular metabolites were
commonly decreased or missing when the mother was lacking a gut 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 greater numbers of axons," Vuong said. "And when we supplemented the pregnant mice with key metabolites that were decreased
or missing when the microbiata was depleted, levels of those metabolites
were restored in the fetal brain and the impairments in axon development
and in offspring behavior were prevented.



==========================================================================
"The gut microbiota has the incredible capability to regulate many
biochemicals not only in the pregnant mother but also in the developing
fetus and fetal brains," Vuong said. "Our findings also pinpoint
select metabolites that promote axon growth." The results suggest that interactions between the microbiota and nervous system begin prenatally
through the influence of the maternal gut microbiota on the fetal brain,
at least in mice.

The applicability of the findings to humans is still unclear, said
the study's senior author, Elaine Hsiao, a UCLA associate professor of integrative biology and physiology, and of microbiology, immunology and molecular genetics in the UCLA College.

"We don't know whether and how the findings may apply to humans,"
said Hsiao, who is also an associate professor of digestive diseases
at the David Geffen School of Medicine at UCLA. "However, there are
many neurodevelopmental disorders that are believed to be caused
by both genetic and environmental risk factors experienced during
pregnancy. Our study suggests that maternal gut microbiota during
pregnancy should also be considered and further studied as a factor
that could potentially influence not only the health of the mother
but the health of the developing offspring as well." Hsiao, Vuong
and colleagues reported in 2019 that serotonin and drugs that target
serotonin, such as antidepressants, can have a major effect on the gut's 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.


========================================================================== Story Source: Materials provided by
University_of_California_-_Los_Angeles. Original written by Stuart
Wolpert. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Helen E. Vuong, Geoffrey N. Pronovost, Drake W. Williams, Elena
J. L.

Coley, Emily L. Siegler, Austin Qiu, Maria Kazantsev, Chantel
J. Wilson, Tomiko Rendon, Elaine Y. Hsiao. The maternal microbiome
modulates fetal neurodevelopment in mice. Nature, 2020; DOI:
10.1038/s41586-020-2745-3 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/09/200923164601.htm

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