Researchers turn autism microbiome theory on its head

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There has been much speculation that the gut microbiome may play a causal role in autism spectrum disorder but new research turns this theory on its head - with researchers arguing the difference in microbial population is due to picky eating in autistic children.

Interest in the autism gut microbiome first came from observations of people on the autism spectrum, revealing they are more likely to experience gut problems, such as constipation and diarrhea.

Further studies suggest children on the autism spectrum had different combinations of bacteria living in their gut. These intriguing relationships inspired studies of mice and rats, some of which indicated the microbiome may cause differences in behaviour.

Out of this momentum emerged speculative therapies claiming to support children with autism by altering the microbiome, including faecal microbiota transfers and diet therapies, which are low on evidence and high in cost.

However, a team of researchers from The University of Queensland, Australia, argue that the evidence linking the microbiome to autism is highly inconsistent and many studies have significant problems with their scientific design. They also point out there are problems in relating mouse studies to humans, because autism does not exist in mice.

In their recent research, published in 'Cell', the team say rather than differences in gut bacteria influencing brain development, changes in gut bacteria are driven by restricted diets, or "picky eating".

No evidence of causal relationship

For their research, the team worked with the Australian Autism Biobank, which includes extensive clinical and biological data from children on the autism spectrum and their families, as well as the Queensland Twin Adolescent Brain Project.

They compared microbial DNA from stool samples of 99 children on the autism spectrum to two groups of non-autistic children: 51 of their siblings and 97 unrelated children.

They also looked at clinical, family and lifestyle information, including about the child's diet, for a comprehensive, broad look at factors that may contribute to the their microbiome.

They found no evidence for a relationship between autism and measures of the microbiome as a whole, or with microbiome diversity.

Only one bacterial species out of more than 600 showed an association with autism - there was no evidence for other bacterial groups that have previously been reported in autism (for example, Prevotella).

Instead, they found children on the autism spectrum were more likely to be "picky eaters"—consistent with reports from earlier studies—and this was related to particular traits associated with autism, such as restricted interests and sensory sensitivity.

They also found pickier eaters tended to have a less diverse microbiome, and runnier stool. 

The genetic information told a similar story: autism and restricted interests corresponded to a less-diverse diet, but not directly with the microbiome.

The team say these genetic data are critical, because they rule out other environmental factors that may have influenced the findings.

They also say microbiome interventions for autism, such as faecal microbiota transplants, should be viewed with caution with the findings suggesting they are unlikely to be effective and may do more harm than good.

The report states: "For future microbiome studies, we emphasize the importance of collecting detailed dietary data, particularly for ASD and other neuropsychiatric traits with plausible co-variation of diet with diagnosis or treatment.

"We also recommend higher-resolution metagenomics technology and expanded databases since more granular taxonomic measures of microbiome composition were more sensitive, gene-level ORMs explained more variance for some traits, power to detect associations was weaker with the MetaPhlAn2/NCBI pipeline, and because taxonomic and functional datasets may capture complementary aspects of the microbiome."

Source: Cell

Yap et al.

Autism-related dietary preferences mediate autism-gut microbiome associations

DOI:https://doi.org/10.1016/j.cell.2021.10.015