New findings in mice suggest yet another role for gut microbes, even before birth.
The microbes residing in a female mouse’s gut help shape the wiring of her offspring’s brain, researchers report September 23 in Nature. While mouse and human development are worlds apart, the study hints at how a mother’s microbiome may have long-term consequences for her offspring.
Scientists have previously found links between a mouse mother’s microbiome and her young’s brain and behavior, but many of those studies worked with animals that were stressed (SN: 7/9/18) or sick. Instead, Helen Vuong, a neurobiologist at UCLA, and her colleagues looked at what a mother’s microbial mix normally does for her pups’ brains.
The new results point to the influence of specific microbes and the small molecules they produce, called metabolites. “Metabolites from the microbiome of the mother can influence the developing brain of the fetus,” says Cathryn Nagler, an immunologist at the University of Chicago who was not involved with the study. The metabolites do this by reaching a developing pup’s brain where they affect the growth of axons, she says. Axons are the threadlike signal-transmitters of nerve cells.
Vuong and her team looked at the brains of fetuses from pregnant mice — some with their usual gut bugs, some raised without microbes and others ridded of their gut bacteria with antibiotics. When a mother’s microbes were missing, fetuses had shorter and fewer axons extending from the brain’s “relay station” to the cortex, Vuong says. These connections are important for processing sensory information.
Those brain differences appear to have consequences for mice later in life. As adults, mice born to microbe-deficient mothers were less sensitive to touch than mice from mothers with a typical microbiome. For instance, in one of several sensory tests, mice from microbe-deficient mothers took longer to notice a small piece of tape stuck to one of their paws. But when microbe-lacking females were given Clostridia bacteria, their offspring’s brain and behavior developed normally. Clostridia are common gut microbes in humans and in mice, Nagler says, and their absence has been linked to some noncommunicable conditions, such as food allergies (SN: 8/26/14).
Small molecules made by the gut bugs may account for this effect. The researchers found that levels of several metabolites in mom’s blood were linked to levels in the fetal blood and brain. “It’s kind of cool that it’s crossing different sites from the mom all the way to the fetus,” Vuong says. That suggests mom shares her gut metabolites with her young.
When pregnant mice with altered microbiomes received supplements of some of those metabolites, their pups’ behavior developed normally. It’s not clear yet how gut microbes and metabolites could be involved in human brain development. Still, this “points now to a way that one might think about intervening,” if pregnant women have deficient microbiomes, says Nagler, who is president of ClostraBio, a company that’s exploring metabolite treatments for diseases related to the immune system. Instead of trying to alter those microbiomes, which can be difficult, pregnant women could receive the needed metabolites directly.
“It will be really important to understand whether these negative effects also happen in humans and whether they lead to long-term medical concerns,” says Carolina Tropini, a microbiologist and biomedical engineer at the University of British Columbia in Vancouver who was not part of the work. Researchers will need to study how the short-term benefits of antibiotics stack up against potential risks, she says, but such research may also lead to therapies for pregnant women who need antibiotics.
