The health of a mother’s microbiome during pregnancy may have a significant impact on her offspring’s risk for autism, according to a new mouse study conducted by researchers at the University of Virginia (UVA) School of Medicine. The microbiome is the collection of microorganisms that naturally live in the gut.
The UVA scientists were able to prevent the development of autism-like neurodevelopmental disorders in lab mice by targeting the maternal microbiome. The findings raise the possibility that preventing some forms of autism could be as simple as an expectant mom modifying her diet or taking custom probiotics.
The scientists also discovered they could halt the development of these same neurodevelopmental disorders by taking another approach: blocking a particular inflammatory molecule produced by the immune system. Targeting this molecule, known as interleukin-17a (IL-17a), offers another potential avenue for preventing autism in people, the researchers say. But they warn that this approach would be much more complex because of the risk of side effects.
“We determined that the microbiome is a key contributor in determining susceptibility [to autism-like disorders], so it suggests that you could target either the maternal microbiome or this inflammatory molecule, IL-17a,” said lead researcher John Lukens, Ph.D., of UVA’s Department of Neuroscience. “You could also use this [IL-17a] as a biomarker for early diagnosis.”
The research sheds light on the complex relationship between the health of the mother’s microbiome and the healthy development of her children.
“The microbiome can shape the developing brain in multiple ways,” said Lukens. “The microbiome is really important to the calibration of how the offspring’s immune system is going to respond to an infection or injury or stress.”
An unhealthy microbiome in the mother can make her unborn offspring susceptible to neurodevelopmental disorders. The researchers found that the IL-17a molecule was a key contributor to the development of autism-like symptoms in lab mice.
The good news is that the microbiome can be easily changed, either through diet, probiotic supplements or fecal transplant. All of these approaches seek to restore a healthy equilibrium among the different microorganisms that live in the gut.
“In terms of translating our work to humans, I think the next big step would be to identify features of the microbiome in pregnant mothers that correlate with autism risk,” Lukens said. “I think the really important thing is to figure out what kind of things can be used to modulate the microbiome in the mother as effectively and safely as we can.”
Blocking IL-17a also might offer a way to prevent autism, but it carries much more risk.
“If you think about pregnancy, the body is basically accepting foreign tissue, which is a baby,” said Lukens. “As a result, maintenance of embryonic health demands a complex balance of immune regulation, so people tend to shy away from manipulating the immune system during pregnancy.”
IL-17a previously has been tied to conditions such as rheumatoid arthritis, multiple sclerosis and psoriasis, and there are already drugs available that target it. But Lukens said that the molecule has an important purpose in stopping infections, especially fungal infections.
Blocking it, he said, “could make you susceptible to all kinds of infections.” And doing so during pregnancy could have complex ripple effects on a child’s development that scientists would need to sort out.
The researchers plan to investigate the potential role of other immune molecules in the development of autism and other such conditions. IL-17a may be just one piece in a much larger puzzle, he said.