A quarterly publication of the Autism Research Institute

The Autism Research Review International is quarterly publication of the Autism Research Institute

Spring, 2024 | Number 2, Volume 38

Mouse study offers new clues about interrelationship of ASD, GI problems, and social behavior

A study conducted by researchers at the Utah School of Medicine offers insights into the association between autism spectrum disorders (ASD) and gastrointestinal (GI) problems, which affect up to 85% of people with ASD. The study also indicates that GI problems may play a causal role in social impairments in ASD, and suggests that two specific types of gut microbes might help to ease GI symptoms.

In the study, D. Garrett Brown and colleagues first dosed mice repeatedly with a substance that produced bouts of colitis and then examined the behavior of the mice after they recovered. The researchers found that animals that experienced repeated colitis did not appear sick, anxious, or depressed afterward, did not exhibit compulsive behaviors, and did not exhibit significant changes in activity. However, the mice did have much less desire to engage in social interactions with new mice. “Overall,” the researchers say, “these data suggest that past, repeated GI insults are associated with abnormal social interactions in mice.”

Next, the researchers explored whether the gut microbiota of individuals with ASD might harbor microbes that make them more vulnerable to GI disease and, as a result, to impairments in social behavior. To investigate this issue, the researchers transplanted fecal samples from five individuals with ASD into mice, using fecal samples from neurotypical family members as controls. They then induced colitis in the offspring of the mice. They report, “Analysis of the data when grouped by family revealed that the microbiota from all but one individual with ASD consistently worsens either weight loss colon shortening [a sign of damage], or both when compared to the respective familial controls.” They conclude that “in most cases, microbiotas from individuals with ASD worsen GI symptoms.”

The researchers also identified two bacterial organisms—Bacteroides uniformis and species of Blautia—that appeared to be protective. “Oral treatment with either of these microbes,” they say, “reduces colon injury in mice.” In addition, they say, treatment with a Blautia isolate from a neurotypical control ameliorated gut injury-associated social engagement deficits in the mice.

Brown and his team say, “Collectively, our data demonstrate that past intestinal distress is associated with changes in active social behavior in mice that can be ameliorated by supplementation of members of the human microbiota.”

The researchers note that while fecal microbiota transplants (FMTs) are currently being tested as a treatment for several conditions, including ASD (see page 3), “the complexity of an FMT makes it difficult to obtain reproducible donor microbiotas.” Moreover, they say, there is also the possibility of transferring dangerous microbes to the recipient. “Thus,” they say, “the identification of specific microbiota members that can ameliorate GI symptoms and modify neurological manifestations will be important for future management of these disorders.”


Citations

“Colitis reduces active social engagement in mice and is ameliorated by supplementation with human microbiota members,” D. Garrett Brown, Michaela Murphy, Roberto Cadeddu, Rickesha Bell, Allison Weis, Tyson Chiaro, Kendra Klag, Jubel Morgan, Hilary Coon, W. Zac Stephens, Marco Bortolato, and June L. Round, Nature Communications, March 30, 2024 (free online). Address: June Round, Department of Pathology, University of Utah School of Medicine, Huntsman Cancer Institute, Division of Microbiology and Immunology, Salt Lake City, UT, [email protected].