Summary: A new study demonstrates the profound influence of gut microbes on behavior, particularly in the context of autism spectrum disorder (ASD). The study reveals that intestinal discomfort in mice reduces social behaviors, a phenomenon reversible by specific bacterial introductions.
This groundbreaking work points to the gut microbiome as both a potential source of ASD-related symptoms and a therapeutic target. By altering the gut microbiome, scientists were able to alleviate not only gastrointestinal symptoms but also behavioral changes, paving the way for microbiome-targeted therapies.
Highlights:
- Gut-behavior link: The study provides strong evidence linking gastrointestinal distress to a reduction in social behaviors in mice, an effect that mirrors the social impairments observed in ASD.
- Microbial intervention: Introduction of specific bacterial strains into the guts of mice improved both gastrointestinal symptoms and associated behavioral changes, highlighting the therapeutic potential of microbiome manipulation.
- Future therapeutic directions: The results suggest that targeted adjustments to the gut microbiome could become a viable strategy to treat gastrointestinal and behavioral symptoms of ASD, leading to personalized microbiome therapies.
Source: University of Utah
For people with autism, constipation, diarrhea, and abdominal pain are often accompanied by the social struggles and repetitive behaviors that define the condition. This has prompted many people to wonder whether gastrointestinal (GI) problems are due to behavioral or sensory features of autism, or whether they might instead contribute to it.
Now, scientists at University of Utah Health have added growing evidence that the microbes that live in our guts influence our behavior. Specifically, they found that in mice, frequent gastrointestinal distress can reduce social behaviors, an effect that persists even after gastrointestinal symptoms disappear.
They also showed that they could alleviate both gastrointestinal symptoms and the behavioral changes they cause by introducing specific species of bacteria into the animals’ intestines.
The new study, published in Natural communicationsdemonstrates that it is possible to impact health and behavior by manipulating the gut microbiome in a controlled manner.
“I think this is a very important therapeutic step because we can now begin to develop therapy with organisms that we know are safe,” says June Round, Ph.D., a microbiologist at University of U Health who led the study. research.
The link between the gut and behavior
Because scientists are still trying to unravel the relationship between gastrointestinal issues and autism-related behaviors, Round and his team began their study by investigating the behavioral impact of gastrointestinal distress in mice. Graduate student Garrett Brown, Ph.D., studied mice with an inflammatory disease called colitis, which causes pain, diarrhea and intestinal damage.
After several rounds of colitis, the animals’ symptoms were allowed to subside before behavioral testing. The mice that suffered from colitis moved normally and showed no signs of anxiety or depression. However, they spent less time interacting with unfamiliar mice than with mice that did not suffer from colitis.
“It’s not like the mice are in so much pain that they don’t do anything,” Brown says. “So maybe it’s something specific to sociability and not just that mice feel bad.”
The reluctance to socialize that the researchers observed in their mice is reminiscent of the social deficits associated with autism. Since their experiments suggested that gut problems might lead to changes in social behavior, they wondered whether the microbes present — which tend to differ between autistic and neurotypical people — might be involved in both.
To investigate, Brown collected stool samples from autistic people as well as their neurotypical parents or siblings. Then he delivered the microbe-filled samples into the mice’s gastrointestinal tracts.
When he induced colitis in these animals, mice carrying microbes from autistic individuals suffered more intestinal damage and lost more weight than mice whose microbes came from neurotypical individuals. It appears that the mixture of microbes collected from neurotypical individuals has a protective effect.
Finding microbial protectants
The microbial community inside the human gut is so complex that the samples the team used in their experiments could easily have included hundreds of types of bacteria, viruses and fungi. Round and Brown wanted to know which of these community members were protecting themselves against intestinal problems.
To do this, Brown compared the gut microbes of autistic individuals to those of their neurotypical family members, as well as to microbes living in the guts of mice transplanted with these microbial communities.
He was looking for potentially protective microbes that might be underrepresented in autistic people compared to neurotypical individuals – and he found some.
“We were able to identify individual microbes that we think might play an important role in resistance to severe colitis,” says Brown, who is now a member of the National Institutes of Health Clinical Center.
Two in particular stood out. Certain species of Blautia bacteria were better represented in neurotypical individuals than in their autistic family members.
And among mice colonized with microbes from autistic people, a group called Bacteroides uniformis was more abundant in those with less severe colitis. B. uniformis is known to be underrepresented in people with irritable bowel syndrome and Crohn’s disease, suggesting a role in gut health.
Once researchers focused on these groups of bacteria, Brown gave them to mice before causing colitis. Blautia and Bacteroides uniformis reduced intestinal problems and Blautia had a corresponding effect on social behavior. Animals given Blautia bacteria were more likely than other mice to interact with unfamiliar mice following colitis.
Towards personalized therapies
Round says the study is one of the first to identify specific organisms within the human microbiota that can ameliorate a behavioral deficit associated with gastrointestinal stress. “This is an example where we are missing microbes, and missing these beneficial microbes leads to disease,” she says.
Further research will be needed to determine whether increasing the number of Blautia or Bacteroides uniformis bacteria could benefit people with gastrointestinal disorders, autism or other conditions. But Round says determining their individual effects is an important step toward personalized microbiome-targeted therapies.
“One day,” she says, “we’ll be able to quickly analyze the microbiome and say, ‘Hey, you’re missing this really important microbe. We’ll give it back to you.’”
About this news on the microbiome, ASD and behavioral research
Author: Jennifer Michalowski
Source: University of Utah
Contact: Jennifer Michalowski – University of Utah
Picture: Image is credited to Neuroscience News
Original research: Free access.
“Colitis Reduces Active Social Engagement in Mice and is Improved by Supplementation with Members of the Human Microbiota” by June Round et al. Natural communications
Abstract
Colitis reduces active social engagement in mice and is improved by supplementation with members of the human microbiota
Multiple neurological disorders are associated with gastrointestinal (GI) symptoms, including autism spectrum disorder (ASD). However, it is unclear whether gastrointestinal distress itself can modify aspects of behavior.
Here, we show that mice with repeated colitis had impaired active social engagement, as measured by interactions with a stranger mouse, even though signs of colitis were no longer present.
We then tested the hypothesis that individuals with ASD harbor microbiota that may differentially influence gastrointestinal health by performing microbiota transplantation studies in germ-free male animals followed by induction of colitis.
Animals that harbor microbiota from individuals with ASD have worsened gut phenotypes compared to animals colonized with microbiota from familial neurotypical (NT) controls.
We identify the enrichment of Blautia species in all familial NT controls and observe an association between high abundance of Bacteroides uniformis and a reduction in intestinal damage. Oral treatment with either of these microbes reduced colon damage in mice.
Finally, the provision of a Blautia isolate of NT control enhances active social engagement associated with intestinal injury in mice. Collectively, our data demonstrate that past intestinal disorders are associated with changes in active social behavior in mice, which can be ameliorated by supplementation with members of the human microbiota.
News Source : neurosciencenews.com
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