Single Species of Gut Bacteria Can Reverse Autism Related Social Behavior: Mouse Study

Summary: Researchers culture a strain of Lactobacillus reuteri from human breast milk and introduced it to mice. They discovered treatment with this bacterial strain appeared to rescue social behaviors.

Source: Cell Press.

The absence of a one specific species of gut bacteria causes social deficits in mice, researchers at Baylor College of Medicine report June 16, 2016 in Cell. By adding this bacteria species back to the guts of affected mice, the researchers were able to reverse some of their behavioral deficits, which are reminiscent of symptoms of autism spectrum disorders (ASDs) in humans. The investigators are now looking to explore the effects of probiotics on neurodevelopmental disorders in future work.

“Other research groups are trying to use drugs or electrical brain stimulation as a way to reverse some of the behavioral symptoms associated with neurodevelopmental disorders — but here we have, perhaps, a new approach,” says senior author Mauro Costa-Mattioli, a neuroscientist at Baylor College of Medicine. “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.”

Diagram shows how dysbiosis causes the autism like behavior in mice.
Buffington next tested whether the specific differences in the microbiome were causative factors underlying the social impairments in offspring of mothers fed a high-fat diet. NeuroscienceNews.com image is credited to Costa-Mattioli et al./Cell Press.

The inspiration for the paper came from human epidemiological studies that have found that maternal obesity during pregnancy could increase children’s risk of developing neurodevelopmental disorders, including ASDs. In addition, some individuals with ASD also report recurring gastrointestinal problems. With emerging research showing how diet can change the gut microbiome and how gut microbes can influence the brain, Costa-Mattioli and his co-authors suspected there could be a connection.

To begin, the researchers fed approximately 60 female mice a high-fat diet that was the rough equivalent of consistently eating fast food multiple times a day. They bred the mice daily and waited for them to bear young. The offspring stayed with their mother for three weeks and then were weaned onto a normal diet. After a month, these offspring showed behavioral deficits, such as spending less time in contact with their peers and not initiating interactions.

“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. So, we used 16S ribosomal RNA gene sequencing to determine the bacterial composition of their gut. We found a clear difference in the microbiota of the two maternal diet groups,” says first author Shelly Buffington, 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.”

Buffington next tested whether the specific differences in the microbiome were causative factors underlying the social impairments in offspring of mothers fed a high-fat diet. Because mice eat each other’s poop, the researchers housed the animals together so that they would 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, a full restoration of the gut microbiome and a concurrent improvement in behavior was observed within four weeks. The investigators concluded that one or more beneficial bacterial species might be important for normal social behavior. Fecal-transplant experiments in mice without microbiota (germ-free mice) provided causal evidence that an imbalanced microbial ecology in the mice born to mothers on a high-fat diet is responsible for their social deficits.

The investigators next wanted to know the specific bacterial species that could be affecting the social behavior of the mice. Whole-genome shotgun sequencing revealed one type of bacteria, Lactobacillus reuteri, which was reduced more than nine-fold in the microbiome of mice born to mothers on the high-fat diet.

“We cultured a strain of Lactobacillus (L.) 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 says. Other ASD-related behaviors, such as anxiety, were not restored by the reconstitution of the bacteria. Interestingly, the authors found that L. reuteri also promoted the production of the “bonding hormone” oxytocin, which is known to play a crucial role in social behavior and has been associated with autism in humans.


Can mom’s diet during pregnancy impact offspring social behavior? In this video, Mauro Costa-Mattioli and colleagues at Baylor College of Medicine describe a potential link between mouse maternal diet-induced changes in the gut microbiome and autism-like social behavior in offspring.

The authors wondered whether the reward circuitry in the socially impaired mice was dysfunctional. “We found that in response to social interaction there was a lack of synaptic potentiation in a key reward area of the brain that could be seen in the normal control mice,” Costa-Mattiol says. “When we put the bacteria back in the maternal-high-fat-diet offspring, we could also restore the changes in synaptic function in the reward circuitry.”

The researchers believe that their work, which uses a human bacteria species to promote oxytocin levels and improve social behavioral deficits in deficient mice, could be explored as a probiotic intervention for the treatment of neurodevelopmental disorders in humans. “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,” Costa-Mattioli says.

About this neuroscience research article

Others who contributed to the research include Gonzalo Viana Di Prisco, Thomas A. Auchtung, Nadim J. Ajami, and Joseph F. Petrosino, all at Baylor College of Medicine.

Funding: The research was supported by funding from the National Institutes of Health, the Alkek Foundation, and Baylor College of Medicine.

Source: Joseph Caputo – Cell Press
Image Source: This NeuroscienceNews.com image is credited to Costa-Mattioli et al./Cell Press
Video Source: The video is credited to Baylor College of Medicine.
Original Research: Full open access research for “Microbial Reconstitution Reverses Maternal Diet-Induced Social and Synaptic Deficits in Offspring” by Shelly A. Buffington, Gonzalo Viana Di Prisco, Thomas A. Auchtung, Nadim J. Ajami, Joseph F. Petrosino, and Mauro Costa-Mattioli in Cell. Published online June 16 2016 doi:10.1016/j.cell.2016.06.001

Cite This NeuroscienceNews.com Article

[cbtabs][cbtab title=”MLA”]Cell Press. “Single Species of Gut Bacteria Can Reverse Autism Related Social Behavior: Mouse Study.” NeuroscienceNews. NeuroscienceNews, 16 June 2016.
<https://neurosciencenews.com/autism-behavior-gut-bacteria-4493/>.[/cbtab][cbtab title=”APA”]Cell Press. (2016, June 16). Single Species of Gut Bacteria Can Reverse Autism Related Social Behavior: Mouse Study. NeuroscienceNew. Retrieved June 16, 2016 from https://neurosciencenews.com/autism-behavior-gut-bacteria-4493/[/cbtab][cbtab title=”Chicago”]Cell Press. “Single Species of Gut Bacteria Can Reverse Autism Related Social Behavior: Mouse Study.” https://neurosciencenews.com/autism-behavior-gut-bacteria-4493/ (accessed June 16, 2016).[/cbtab][/cbtabs]


Abstract

Microbial Reconstitution Reverses Maternal Diet-Induced Social and Synaptic Deficits in Offspring

Highlights
•Maternal high-fat diet (MHFD) induces behavioral alterations in offspring
•MHFD causes alterations in gut microbial ecology in offspring
•MHFD offspring show deficient synaptic plasticity in the VTA and oxytocin production
•L. reuteri treatment restores oxytocin levels, VTA plasticity and social behaviors

Summary
Maternal obesity during pregnancy has been associated with increased risk of neurodevelopmental disorders, including autism spectrum disorder (ASD), in offspring. Here, we report that maternal high-fat diet (MHFD) induces a shift in microbial ecology that negatively impacts offspring social behavior. Social deficits and gut microbiota dysbiosis in MHFD offspring are prevented by co-housing with offspring of mothers on a regular diet (MRD) and transferable to germ-free mice. In addition, social interaction induces synaptic potentiation (LTP) in the ventral tegmental area (VTA) of MRD, but not MHFD offspring. Moreover, MHFD offspring had fewer oxytocin immunoreactive neurons in the hypothalamus. Using metagenomics and precision microbiota reconstitution, we identified a single commensal strain that corrects oxytocin levels, LTP, and social deficits in MHFD offspring. Our findings causally link maternal diet, gut microbial imbalance, VTA plasticity, and behavior and suggest that probiotic treatment may relieve specific behavioral abnormalities associated with neurodevelopmental disorders.

“Microbial Reconstitution Reverses Maternal Diet-Induced Social and Synaptic Deficits in Offspring” by Shelly A. Buffington, Gonzalo Viana Di Prisco, Thomas A. Auchtung, Nadim J. Ajami, Joseph F. Petrosino, and Mauro Costa-Mattioli in Cell. Published online June 16 2016 doi:10.1016/j.cell.2016.06.001

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