Human microbiota transplant transfers autism phenotype to mice.
Autism spectrum disorder (ASD) affects an estimated one in 59 people in the United States, causing adverse social communication and repetitive behaviour. Many factors, including genetic and environmental effects, are believed to influence symptoms, however, there are no approved treatments. Now, a study from researchers led by Caltech shows that gut microbiota directly contribute to autism-like behaviour in mice. The team state they successfully transplanted gut microbiota from human donors with ASD into germ-free mice, to show that colonization with ASD microbiota is sufficient to induce hallmark autistic behaviour. The opensource study is published in the journal Cell.
Previous studies show the communities of microorganisms which inhabit the human gut are called the microbiota, and their collective genomes are known as the microbiome. These organisms live in a symbiotic state with humans, helping to digest food, affecting metabolism, and educating the host’s immune system. The current study examines the microbiota’s role in autism-like behaviour in mice, using ‘germ-free’ mice, animals grown in the absence of microorganisms.
The current study transfers gut bacteria from children with autism into mice via faecal transplantation, and samples from people without autism were transplanted into other groups of animals. Results show the mice with microbiota from individuals with ASD exhibited autism-like behaviours, whereas the mice containing microbiota from control non-ASD individuals did not show these symptoms. Data findings show the ASD exhibiting mice spent less time socially interacting with other mice, vocalized less, and displayed repetitive behaviour; these symptoms are known behavioural characteristics of people with ASD.
The lab observed, in addition to the behavioural differences, mice colonized with human ASD microbiota also showed altered gene expression in their brains and differences in the types of microbial metabolites, or products, present. The group state two metabolites in particular were found in lower amounts in the mice, namely, 5-aminovaleric acid (5AV) and taurine. They go on to explain that ASD has been characterized by an imbalance in the ratio of excitation and inhibition in the brain in certain cases, and posit the lower amounts of 5AV and taurine are in line with this finding, as both affect certain inhibitory neural receptors called GABA receptors.
The team surmise their data suggest a mechanism of action involving the production of microbial metabolites in the gut which affect brain function and manifest atypical ASD behaviour. For the future, researchers state these findings do not indicate that the gut microbes cause autism, and therefore additional studies are needed to address the impact of gut bacteria in humans.