The biological roots of autism continue to mystify scientists, despite a wealth of genetic, cellular, and microbial research data.
But a recent focus on the human microbiome — the ecosystem of microbes that reside in our gut — offers a promising area of exploration.
These microbes have been shown to play a part in autism, but the exact mechanisms remain unclear.
A fresh computational approach to the problem has now provided some new insights.
A study published in Nature Neuroscience, led by the Simons Foundation’s Autism Research Initiative (SFARI), reanalyses dozens of previously published datasets and offers compelling findings about the link between the microbiome and autism.
Big Data, New Insights
The large-scale study united seemingly disparate data from different studies, finding a microbial signature that distinguishes autistic individuals from neurotypical ones across many datasets.
“We were able to identify a microbial signature that distinguishes autistic from neurotypical individuals across many studies,” says Jamie Morton, one of the study’s corresponding authors, and an independent consultant.
The research brings together leaders in computational biology, engineering, medicine, autism, and the microbiome from institutions across North America, South America, Europe, and Asia.
Seeking Signals in the Noise
However, the complexity of autism and the microbiome presents unique challenges. Autism presents heterogeneously — autistic individuals differ from each other genetically, physiologically, and behaviorally.
The microbiome, meanwhile, presents its own complexities. Most studies have been one-time snapshots of the microbial populations present in autistic individuals, limiting the potential insights they can provide.
Addressing these complexities, the research team developed an algorithm to reanalyze 25 previously published datasets containing microbiome and other data — such as gene expression, immune system response, and diet — from both autistic and neurotypical cohorts.
This approach enabled them to identify microbes that have differing abundances between autistic and neurotypical individuals.
Unexpected Findings
Their analysis identified autism-specific metabolic pathways associated with particular human gut microbes, which also appeared elsewhere in autistic individuals, from their brain-associated gene expression profiles to their diets.
“We hadn’t seen this kind of clear overlap between gut microbial and human metabolic pathways in autism before,” says Morton.
The researchers also found an overlap between microbes associated with autism, and those identified in a recent long-term fecal microbiota transplant study.
The Road Ahead
Future research should focus on long-term studies that involve interventions, to help identify cause-and-effect relationships, say the researchers.
Beyond autism, these findings could potentially be applied across other areas of biomedicine that have long been challenging, from depression to Parkinson’s to cancer.
“Before this, we had smoke indicating the microbiome was involved in autism, and now we have fire.
We can apply this approach to many other areas, where we think the microbiome plays a role, but where we don’t yet know exactly what the role is,” says Rob Knight, director of the Center for Microbiome Innovation at the University of California San Diego, and a study co-author.
For more information about health, please see recent studies about rare blood clots after COVID-19 vaccination, and gut health plays a role in autism.
The study was published in Nature Neuroscience. Follow us on Twitter for more articles about this topic.
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