Christopher Boone does not like to be touched and screams every time anyone tries to grab him or even grazes him in passing. He hates yellow and brown, and talking to strangers, but loves astronomy and maths. And he dreams that one day he’ll become an astronaut. Christopher Boone has an Autism Spectrum Disorder (ASD). He became popular—and has been ever since—more than a decade ago as the main character of the 2003 bestselling novel “The Curious Incident of the Dog in the Night-Time”, by British writer Mark Haddon.
According to World Health Organisation one child in 160 worldwide has ASD, a developmental condition characterized by impairments in social interactions and behaviour (estimates in the US are now as high as one in 68). Scientists have usually associated it with abnormalities in brain structure and function, due to genetic factors.
But now a new study by researchers at Baylor College of Medicine (Houston, Texas, USA), published in the journal Cell, boosts the emerging theory that gut microbiota also plays a key role in some autism-associated behaviours.
In a study with mice, they have been able to show there is a clear link between gut bacteria, obesity and social behaviour. And, more interestingly, they have managed to demonstrate that treating autistic-like animals with some specific microbial species they lacked could reverse some of their social deficits. These findings may open the door to probiotics to treat neurodevelopmental disorders in the future. “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”, says senior author Dr Mauro Costa-Mattioli, associate professor of neuroscience at Baylor and main author of this research in a press release.
“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”, he adds.
Maternal obesity linked to autism
Previous epidemiological studies had found that maternal obesity during pregnancy could increase the newborn’s risk of developing neurodevelopmental disorders, including ASD. Moreover, in research carried out in humans and also non-human primates, the offspring of obese mothers had also an altered gut microbiota. In fact, people with ASD frequently suffer from recurring gastrointestinal problems.
Neuroscientist Dr. Mauro Costa-Mattioli suspected there might be a link between all those factors and decided to explore it. In an experiment with mice, he and his lab colleagues fed female mice a high-fat diet, the equivalent of eating fast food several times a day for humans. Then, they bred them and observed that “a large proportion” of the pups showed ASD-like behaviours: they didn’t interact with their littermates or show any interest in new objects, and showed repetitive actions. They were also anxious.
Costa-Mattioli and his group found clear differences between these newborn rodents’ microbiota compared with the control group’s. To find out whether these bacterial changes between groups could affect behaviour, they decided to put the rodents born to mothers fed with high-fat diet (MHFD) in the same cage as control mice newborns.
Mice are coprophagic—that is, they have the habit of eating each other’s poop. And researchers observed that when together, the first ones developed a similar gut microbiota to the control group and what’s more, they had more normal social interactions.
These findings made the investigators wonder whether the microbes in the mouse intestines were responsible for restoring social behaviour. To answer this question, they carried out fecal transplants from control mice to germ-free mice, which also have some ASD-like behaviour, and saw they could restore some of their social abilities.
One single culprit
Then, they tested to find out whether one or more beneficial bacterial species might be important for normal social behaviour. So investigators sequenced the gut microbiota and found that one single type of bacteria, called Lactobacillus reuteri, was nine times higher in the control group pups than in those born to MHFD. Interestingly, a previous study (also in rodents) had shown that this specific bacterial strain promoted the release of oxytocin, the so-called bonding hormone key to normal social behaviour in mammals.
“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 behaviour,” says first author Shelly Buffington, a postdoctoral fellow in Costa-Mattioli’s lab. Other ASD-like behaviours in the mice, however, such as anxiety, were not restored.
In the brain
The findings of this study did not stop there. The scientists were also able to show that L. reuteri treatment reversed abnormalities in the reward circuitry of the brains of MHFD mouse offspring with impaired social interactions.
“When we put the bacteria back in the maternal-high-fat-diet offspring, we could also restore the changes in the synaptic function in the reward circuitry”, Costa-Mattioli says.
The researchers are now looking to explore the effects of probiotics on neurodevelopmental disorders in future work.
Buffington SA, De Prisco GV, Auchtung TA, Ajami NJ, Petrosino JF, Costa-Mattioli M. Microbial reconstitution reverses maternal diet-induced social and synaptic deficits in offspring. Cell. 2016; 165(7):1762-75. doi:10.1016/j.cell.2016.06.001, 2016
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