Bacterial populations in mother's GI tract may play a central role.

Mothers who experience an infection severe enough to require hospitalization during pregnancy are at higher risk of having a child with autism. Two new studies from MIT and the University of Massachusetts Medical School shed more light on this phenomenon and identify possible approaches to preventing it. In research on mice, the researchers found that the composition of bacterial populations in the mother’s digestive tract can influence whether maternal infection leads to autistic-like behaviors in offspring. They also discovered the specific brain changes that produce these behaviors.

“We identified a very discrete brain region that seems to be modulating all the behaviors associated with this particular model of neurodevelopmental disorder,” said Gloria Choi, the Samuel A. Goldblith Career Development Assistant Professor of Brain and Cognitive Sciences and a member of MIT’s McGovern Institute for Brain Research.

If further validated in human studies, the findings could offer a possible way to reduce the risk of autism, which would involve blocking the function of certain strains of bacteria found in the maternal gut, the researchers said.

Choi and Jun Huh, formerly an assistant professor at UMass Medical School who is now a faculty member at Harvard Medical School, are the senior authors of both papers, which appeared in the journal Nature on September 13. MIT postdoc Yeong Shin Yim is the first author of one paper, and UMass Medical School visiting scholars Sangdoo Kim and Hyunju Kim are the lead authors of the other.

A key clue was that when immune systems in some of the pregnant mice were stimulated, they began producing IL-17 within a day. “Normally it takes three to five days, because IL-17 is produced by specialized immune cells and they require time to differentiate,” Huh said. “We thought that perhaps this cytokine is being produced not from differentiating immune cells, but rather from pre-existing immune cells.”

Previous studies in mice and humans have found populations of Th17 cells in the intestines of healthy individuals. These cells, which help to protect the host from harmful microbes, are thought to be produced after exposure to particular types of harmless bacteria that associate with the epithelium.

The researchers found that only the offspring of mice with one specific type of harmless bacteria, known as segmented filamentous bacteria, had behavioral abnormalities and cortical patches. When the researchers killed those bacteria with antibiotics, the mice produced normal offspring.

“This data strongly suggests that perhaps certain mothers who happen to carry these types of Th17 cell-inducing bacteria in their gut may be susceptible to this inflammation-induced condition,” Huh said.

Humans can also carry strains of gut bacteria known to drive production of Th17 cells, and the researchers plan to investigate whether the presence of these bacteria is associated with autism.

Sarah Gaffen, a professor of rheumatology and clinical immunology at the University of Pittsburgh, said the study clearly demonstrates the link between IL-17 and the neurological effects seen in the mice offspring. “It’s rare for things to fit into such a clear model, where you can identify a single molecule that does what you predicted,” said Gaffen, who was not involved in the study.