Gut bacteria linked to autism in mice

 

One specific species of gut bacteria seems to determine whether mice exhibit autism spectrum disorder-type traits, researchers have found. 

When the microbe was removed, the animals showed social deficits, when it was added back, some of the mice’s behaviour was reversed.

The researchers, who published their work in Cell, say the findings opened possibilities for a new approach to treatment.

“Whether it would be effective in humans, we don’t know yet, but it is an extremely exciting way of affecting the brain from the gut,” said senior author Mauro Costa-Mattioli, of Baylor College of Medicine in Texas.

“Other research groups are trying to use drugs or electrical brain stimulation as a way to reverse some of the behavioural symptoms associated with neurodevelopmental disorders – but here we have, perhaps, a new approach.”

There is mounting evidence that diet can change the gut microbiome and that gut microbes can influence the brain.

Epidemiological studies have found that maternal obesity during pregnancy can increase children’s risk of developing neurodevelopmental disorders, including Autism Spectrum Disorders (ASDs). 

That research, combined with the fact that some individuals with ASD also report recurring gastrointestinal problems, led Costa-Mattioli and his co-authors to suspect there could be a connection.

As a first step, the scientists fed around 60 female mice a high-fat diet – akin to a human eating fast food several times a day. 

The offspring of the mice showed behavioural deficits, such as spending less time in contact with their peers and not initiating interactions.

“First we wanted to see whether 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,” said Costa-Mattioli. 

Using gene sequencing to determine the bacterial composition of their gut, the team found a clear difference in the microbiota of the two maternal diet groups.

“The sequencing data was so consistent that by looking at the microbiome of an individual mouse we could predict whether its behaviour would be impaired,” first author Shelly Buffington said.

She next tested whether the specific differences in the microbiome were factors in causing the the social impairments in offspring of mothers fed a high-fat diet.

Mice eat each other’s faeces, so it was simple matter to get them to acquire microbiota from their cagemates. 

When socially impaired three-week-old mice born to mothers on a high-fat diet were paired with normal mice, there was a full restoration of the gut microbiome and a concurrent improvement in behaviour within four weeks.

The investigators concluded that one or more beneficial bacterial species might be important for normal social behaviour. 

Further investigation revealed one type of bacteria, Lactobacillus reuteri, was 900% less common in the microbiome of mice born to mothers on the high-fat diet.

“We cultured a strain of L. reuteri originally isolated from human breast milk and introduced it into the water of the high-fat-diet offspring,” said Buffinton.

“We found that treatment with this single bacterial strain was able to rescue their social behaviour.”

Other ASD-related behaviours, such as anxiety, however, were not restored by the reconstitution of the bacteria. But L. reuteri appeared to promote the production of the “bonding hormone” oxytocin, which is known to play a crucial role in social behaviour and has been associated with autism in humans.