Can a disrupted gut microbiome cause autism?

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The effect of the gut microbiome on health is so important that it is sometimes called a forgotten organ. The trillions of critters in the lower digestive tract have an influence that seems to spread throughout the body, helping to regulate weight, for example. In recent years, however, one idea in particular has intrigued researchers. This is because certain mixtures of gut microbes can help induce autism.

It is well known that autistic children suffer from gastroenteric problems. They also often appear to have simpler gut flora than their neurotypical peers, and some observations report the presence of unusual species. This has led to the suggestion that these abnormal microecosystems could actually trigger autism. This thought is so tempting that preliminary experiments designed to alter the microbiomes of children with autism have been conducted, with apparently positive results.

Unfortunately, the theory that gut microbes can cause autism has some fragile foundations. The best evidence comes from work with mice, which is problematic because identifying patterns of murine behavior that correspond to human autism is as much an art as it is a science. Work on people, meanwhile, has been criticized for relying on samples too small to give statistically definitive conclusions.

But not anymore. A study published in Cell by Jacob Gratten of the University of Queensland, Australia, and colleagues is believed to have enough statistical power to answer the question robustly. And that answer is “no”, gut microbes do not cause autism. Dr. Gratten’s work indicates that, while there is indeed a correlation to be explained, it is in fact autism that affects (albeit indirectly) the intestinal flora, and not the other way around.

Dr Gratten and his colleagues started their project in 2016, using stool samples and dietary information collected from two large studies, the Australian Autism Biobank and the Queensland Twin Adolescent Brain Project. Of the 247 children they selected for inclusion, 99 had been diagnosed with autism, 51 were neurotypical siblings of some of them, and the rest were unrelated neurotypical children.

They found that there was a clear link between the dietary diversity of each child and the diversity of their gut microbes, with more adventurous diets being associated with richer microbiomes. And because the sensory experiences associated with new foods can be overwhelming for them, children with autism are more likely than others to have a restricted diet. Subtracting this effect left no signal remaining. The team therefore found no link between autism and microbial diversity beyond that caused by the dietary preferences of children with autism. There was also no detectable link between autism and particular bacterial species of the type suggested by previous studies.

At first glance, this contradicts the findings of the Microbiome Treatment Camp, led by Rosa Krajmalnik-Brown of Arizona State University. His early studies, though few in number, suggested fecal transplants, used in extreme cases to treat infection with an intestinal insect called Clostridium difficile– had a positive effect on the behavioral traits of children with the autism spectrum, as well as on their gastrointestinal symptoms. She is now overseeing clinical trials to test these results more robustly.

It remains to be seen whether there really is a contradiction. Dr Krajmalnik-Brown, while acknowledging the quality of Dr Gratten’s analysis, still thinks she cannot explain the results she saw in the preliminary trials. But it is also possible that fecal transplantation, by relieving the uncomfortable symptoms caused directly by imbalanced microbiomes, improves the behavior of children with autism, without affecting the neural foundations of the disease.

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