Epidemiological studies that have determined that obesity during pregnancy may increase the risk of having a baby with neurodevelopmental disorders such as ASDs. Additionally, gastrointestinal disorders and related symptoms are commonly reported in people with ASDs. Research on the microbiome has expanded to many areas, including demonstrating that as diet can alter the gut microbiome, the microbiome can then influence on the brain. So the researchers wanted to investigate whether there might be a connection between the microbiome and ASDs.
The scientists started by feeding a large group of female mice a high-fat diet, roughly simulating eating multiple fast food meals every day. After breeding these mice, the offspring were kept with their mother for three weeks, and were then put on a normal diet. The researchers observed that these offspring had behavioral deficits; they were not initiating contact or spending much time with their peers. They discuss this research in the video below.
"First we wanted to see if there was a difference in the microbiome between the offspring of mouse mothers fed a normal diet versus those of mothers fed a high-fat diet. “ The team used genetic sequencing to analyze the bacterial composition of the gut. “We found a clear difference in the microbiota of the two maternal diet groups," says the first author of the study, Shelly Buffington, who is a postdoctoral fellow in Costa-Mattioli's lab. "The sequencing data was so consistent that by looking at the microbiome of an individual mouse we could predict whether its behavior would be impaired."
To test whether the microbiome could be causing the behavior issues, they housed mice that were socially impaired and born to dams on a high-fat diet with mice that were born to normal mothers. Mice are coprophagic (they eat each other's feces) and as such, they transfer gut microbiota back and forth. After cohabitation, complete restoration of the gut microbiome was seen, along with a simultaneous improvement in behavior, within four weeks. These observations were confirmed when the team performed fecal-transplants on germ-free mice, establishing causal evidence that an imbalanced microbiome in mice born to dams on a high-fat diet is to blame for their social impairments. It was concluded that one or more bacterial species may be vital for normal social behavior.
"We cultured a strain of Lactobacillus reuteri originally isolated from human breast milk and introduced it into the water of the high-fat-diet offspring. We found that treatment with this single bacterial strain was able to rescue their social behavior," Buffington explains. It did not correct the anxiety seen in the mice, however.
Digging deeper, the investigators determined that L. reuteri promotes the production of oxytocin, a hormone that is known to play a critical role in social behavior and has also been connected with autism in humans.
The researchers suggest that probiotic intervention for the treatment of neurodevelopmental disorders in humans is an avenue to explore. "This is where the science is unexpectedly leading us. We could potentially see this type of approach developing quite quickly not only for the treatment of ASD but also for other neurodevelopmental disorders; anyway, this is my gut feeling," elaborates Costa-Mattioli.
Sources: Cell, Cell Press via Science Daily