The microbiota that resides in the human gut has been shown to play a role in autism, but the mechanisms of this link are still fraught with uncertainty. A study published today in Nature Neuroscience takes a new computational approach to this question, shedding new light on the relationship between the microbiome and autism.

Despite a growing body of research looking at more and more genetic, cellular, and microbial data, the biological roots of autism continue to baffle researchers. Recently, scientists have focused their attention on a new and promising field: the microbiome. The microbiota in the human gut has been shown to play a role in autism, but the mechanisms of this link are still fraught with uncertainty. A study published today in Nature Neuroscience takes a new computational approach to this question, shedding new light on the relationship between the microbiome and autism. The study, which stemmed from the Simons Foundation’s Autism Research Initiative (SFARI) and involved an innovative reanalysis of dozens of previously published datasets, aligns with a recent long-term study of people with autism that focused on the microbiome for therapeutic interventions. The findings also underscore the importance of longitudinal studies in elucidating the interactions between the microbiome and complex disorders such as autism.

Author Jamie Morton said, “We were able to coordinate seemingly disparate data from different studies and find a common language to unify them.” With this, we were able to identify microbial signatures that distinguish autistic and neurotypical individuals in many studies, but the larger point is that going forward, we need robust long-term studies that look at as many datasets as possible and understand how they change at the time of [treatment] intervention.”

The study, with 43 authors, brings together leaders in computational biology, engineering, medicine, autism, and the microbiome from institutions in North and South America, Europe, and Asia. “The sheer number of fields and areas of expertise in this large-scale collaboration is noteworthy and necessary to get a new and consistent picture of autism,” said Rob Knight, director of the Center for Microbiome Innovation at the University of California San Diego and co-author of the study.

Autism is inherently complex, and research trying to identify the specific gut microbes involved in autism has been plagued by this complexity. First, autism presents in heterogeneous ways – individuals with autism are genetically, physiologically, and behaviorally different from one another. Second, the microbiome presents unique difficulties. Microbiome studies typically report only the relative proportions of specific microbes, requiring sophisticated statistics to understand which microbial population changes are associated with conditions of interest. This makes it difficult to find signals in the noise. To complicate matters further, most studies to date have been one-off snapshots of microbial populations in autistic people. “The power of a point in time is limited; Tomorrow or next week could be very different.”


“We wanted to address the evolving question of the relationship between the microbiome and autism and thought, ‘Let’s go back to the existing data set and see how much we can learn from it.'”

In the new study, the team developed an algorithm to reanalyze 25 previously published datasets containing microbiome and other “omics” information – such as gene expression, immune system responses, and diet – from both autistic and neuronormal populations. In each dataset, the algorithm found the best pairings of autistic and neurotypical individuals in terms of age and gender, two factors that often confuse autism research. “Instead of comparing the average cohort results in the study, we treated each pair as a single data point and were therefore able to analyze more than 600 asd control pairs simultaneously, corresponding to an actual cohort of more than 1,200 children,” Taroncher-Oldenburg said. “From a technical point of view, this requires the development of new computational methods,” he added. Their new computational approach allowed them to reliably identify microbes that differ in abundance between ASD and neuronormal individuals.

To the researchers’ surprise, their analysis identified metabolic pathways unique to autism linked to specific human gut microbes. Importantly, these pathways are also seen elsewhere in people with autism, from their brain-related gene expression profiles to their diet. “We hadn’t seen this clear overlap between gut microbes and human metabolic pathways in people with autism before,” Morton said.

Even more striking was the overlap between the microbes associated with autism and those found in a recent long-term fecal microbiome transplant study led by James Adams and Rosa Krajmalnik-Brown of Arizona State University’s Center for Microbiome Health BioDesign. “Another set of eyes looked at the problem from a different Angle, and they confirmed our findings,” said Krajmalnik-Brown, who was not involved in the study published today.

“The significance of this work lies not only in the identification of major features, but also in computational analysis that identifies the need for future research, including longitudinal, well-designed measurements and controls to achieve robust interpretations,” said Kelsey Martin.

“Going forward, we need more long-term studies involving interventions so we can understand cause and effect.” Citing compliance issues that traditional long-term studies often face, Taroncher-Oldenburg suggested that study design could more effectively take into account the reality of long-term microbiome sampling in people with autism. “The actual clinical limitations must inform the statistics, which will inform the study design,” he said. In addition, he noted, long-term studies can reveal insights about groups and individuals, and how individuals respond to specific interventions over time.

Importantly, the researchers say the findings extend beyond autism. The approach presented here can also be applied to other biomedical fields that have long proved challenging. “Before this, we had smoke indicating that the microbiome was linked to autism, and now we have fire.” “We can apply this approach to many other areas, from depression to Parkinson’s to cancer, where we think the microbiome plays a role, but we don’t know exactly what role yet.”

The Nature sub-journal sheds light on the link between autism and the microbiome, which could have a positive impact on the organic fertilizer market. Since this study sheds light on the potential role of the gut microbiome in autism, there may be an increased focus on gut health and microbiome balance. This could trigger an increase in demand for organic food and organic agriculture, which uses more environmentally friendly and microbial-friendly methods, avoiding the use of chemical pesticides and fertilizers, thereby protecting soil ecosystems and the diversity of the microbiome.

Therefore, the organic fertilizer market is likely to be driven by the growth demand. Farmers and gardeners may be more inclined to use organic fertilizers to improve soil quality, increase microbial activity, and improve the health and quality of crops. This is likely to boost the organic fertilizer market and encourage more investment and innovation to meet the potential market demand. However, the specific market impact also depends on a number of factors, such as consumer awareness, government policies, and changes in agricultural practices.

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