For people with autism, gastrointestinal (GI) issues like constipation, diarrhea, and abdominal pain are frequently experienced alongside the social struggles and repetitive behaviors that are commonly associated with the condition. This has raised a critical question: do these gastrointestinal problems arise due to autism’s behavioral or sensory features, or could they actually contribute to the behaviors and social challenges observed in autism? Understanding this connection could open new therapeutic avenues, particularly in light of recent discoveries that point to a complex relationship between the gut microbiome and behavior.
A recent study conducted by scientists at University of Utah Health adds to the growing body of evidence suggesting that the microbes living in our gut have a significant influence on behavior. Specifically, their research found that frequent gastrointestinal distress in mice can reduce social behaviors—an effect that lasts even after the GI symptoms have subsided. The study also demonstrated that introducing specific species of bacteria into the mice’s gut could alleviate both the GI symptoms and the behavioral changes triggered by them.
The study, published in Nature Communications, shows that it is possible to impact both health and behavior by manipulating the gut microbiome in a controlled manner. This discovery has profound implications for the treatment of conditions like autism, where behavioral challenges and GI issues often go hand in hand.
“I think that this is a really important step therapeutically, because now we can start to assemble a therapy with organisms that we know to be safe,” says June Round, Ph.D., a microbiologist at U of U Health who led the research.
“…now we can start to assemble a therapy with organisms that we know to be safe.”
— June Round, Ph.D.
The Gut-Behavior Connection
The relationship between gastrointestinal problems and autism-related behaviors remains a puzzle that scientists are still working to solve. Round and her team began their investigation by studying how GI distress might impact behavior in mice. Graduate student Garrett Brown, Ph.D., focused on mice with an inflammatory condition known as colitis, which causes pain, diarrhea, and intestinal damage. After inducing several rounds of colitis in the mice, the researchers allowed the symptoms to subside before testing the animals’ behavior.
Interestingly, the mice that had experienced colitis appeared to move around normally and showed no signs of anxiety or depression. However, they spent significantly less time interacting with unfamiliar mice than those that had never experienced colitis. “It’s not like the mice are under so much pain that they’re not doing anything,” Brown explains. “So maybe it is something specific to sociability and not just that the mice feel poorly.”
This reluctance to socialize was strikingly similar to the social impairments observed in individuals with autism. Given this, the researchers began to suspect that gastrointestinal problems might influence social behavior. They also wondered whether the microbes in the gut—microbes which differ between autistic and neurotypical individuals—might be involved in this process.
Investigating the Microbial Influence
To explore this hypothesis further, Brown collected stool samples from individuals with autism, as well as from their neurotypical family members, including parents and siblings. The team then transplanted these microbiota into the GI tracts of mice. When colitis was induced in these mice, those with microbiota from individuals with autism experienced more severe intestinal damage and lost more weight compared to those that received microbiota from neurotypical individuals. Interestingly, the microbial communities from neurotypical individuals seemed to offer some protective benefits.
This finding pointed to the possibility that certain microbes might play a protective role in preventing or mitigating GI problems and the resulting behavioral changes.
Finding Microbial Protectors
The complexity of the human gut microbiome is vast, and the microbial samples used in the experiments contained hundreds, if not thousands, of different species of bacteria, viruses, and fungi. Round and Brown wanted to identify which specific microbes might be contributing to the observed protective effects. To do this, they compared the gut microbes of individuals with autism to those of their neurotypical family members and analyzed the impact of these microbes on the health and behavior of mice.
Through this process, they were able to identify certain microbes that appeared to be underrepresented in people with autism compared to their neurotypical family members. Two microbes stood out as particularly promising. Blautia bacteria, which were more common in neurotypical individuals, seemed to play a role in protecting against severe colitis. On the other hand, a species called Bacteroides uniformis was found to be more abundant in mice that experienced less severe colitis, suggesting that it might help maintain intestinal health.
Both of these bacteria were then introduced to mice prior to inducing colitis, and the results were striking. Not only did both Blautia and Bacteroides uniformis help reduce intestinal distress, but Blautia also had a positive impact on social behavior. Mice treated with Blautia were more likely to engage with unfamiliar mice, which is significant given the social impairments that are characteristic of autism.
Toward Personalized Therapies
Round and her team’s study represents one of the first to identify specific organisms within the human microbiome that could alleviate behavioral deficits associated with GI stress. “This is an example where we are missing microbes, and missing these beneficial microbes is driving disease,” Round explains.
While further research is needed to determine whether boosting the populations of Blautia or Bacteroides uniformis bacteria could benefit individuals with GI disorders, autism, or other related conditions, the study lays the groundwork for personalized microbiome-targeted therapies. This could one day lead to a future where gut bacteria are analyzed and restored to improve both physical health and social behaviors in individuals with autism.
“One day,” Round says, “we’re going to be able to quickly analyze the microbiome and say, ‘Hey, you’re missing this really important microbe. We’re going to give it back to you.’”
By understanding how gut microbes influence social behavior, we may be on the brink of a new era of autism treatments that address both the social challenges and gastrointestinal issues that many individuals with autism face.
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