Gut microbes from autistic children can alter behavior in mice. It has been observed that mice colonized with intestinal microbes from some autistic children show behaviors similar to those of children. The results have provided the first evidence that gut microbes could contribute to the symptoms of autism.

Experts found evidence that the microbes of autistic children produce unusually low levels of two small molecules. Delivering these molecules to a mouse model facilitates some of the autism-like traits of mice.

The results obtained are based on stool samples from only 11 children with autism and 5 controls. But if confirmed, they may lead to a better understanding of the brain-gut connection in autism.

Sarkis Mazmanian, the lead researcher, says this opens up the possibility that changes in the microbiome may contribute to symptoms. Therefore, if this correlation is confirmed, then the potential for interventions opens up.

It is proven that approximately 40% of children with autism have digestive problems, facilitating the possibility of suffering from an altered intestinal microbiome. A 2017 pilot study found that fecal transplants from neurotypical people alleviate intestinal problems and social difficulties in some autistic children, suggesting that microbes could help treat this disorder.

The new findings are consistent with studies showing that germ-free mice that received fecal transplants from people with depression, Parkinson's disease or schizophrenia adopt the behavioral characteristics of their donors.

In the study, researchers isolated microbes from the stool of five controls, three children with mild autism and eight with more severe features. They transplanted each set of microbes into “germ-free” male and female mice, which lack a microbiome, when the mice were about 4 weeks old. Three weeks later, the researchers bred pairs of mice that had received transplants from the same child. They designed the study this way, so they could analyze the effects of microbial transplants on brain development and behavior. (Mouse pups typically inherit their gut microbes from their mother.)

At 6 weeks of age, pups whose mothers received microbes from a child with mild autism traits behave the same as those with microbes from controls. But mice whose mothers received microbes from a child with severe autism spent less time socializing, made fewer vocalizations, and displayed more repetitive behaviors than controls. The effect is more pronounced in male offspring than in female offspring.

The brains of microbial offspring from autistic donors also show an unusual increase in genes involved in "alternative splicing," the process by which a cell generates different proteins from the same gene. They also show alternative splicing of 560 genes, including 11 with strong links to autism.

Mice transplanted from children with severe autism have less microbial diversity than those transplanted from controls, and tend to have unusual proportions of certain bacteria. These mice also have unusual levels of 27 small molecules in their guts. Two of these molecules are taurine and 5-aminovaleric acid, which activate receptors for the chemical messenger gamma-aminobutyric acid (GABA). Low levels of GABA are implicated in autism.

The team found that offspring treated with these molecules are more sociable and have fewer repetitive behaviors than controls. The treatments have a similar effect on social behavior, but not repetitive behavior, in the germ-infected offspring of an autistic child.

Mazmanian's team is exploring which receptors mediate the effects of the two molecules in the brain. Just as they are testing other small molecules and microbes as treatments in mice.

References:

Sharon G. et al. Cell 177, 1-19 (2019) Abstract

Text adapted by MARIONA ALSEDÀ