Study sheds new light on link between gut microbiome and autism

The biological causes of autism continue to baffle researchers, despite a growing body of research examining a growing body of genetic, cellular, and microbial data. Recently, scientists have focused on a new and promising area of ​​focus: the microbiome. This collection of microbes that live in the human gut has been shown to play a role in autism, but the mechanisms underlying this relationship remain obscure. Research that employs a new computational approach to this problem is published today. natural neuroscience Shining new light on the relationship between the microbiome and autism. This study -; it stemmed from the Simons Foundation’s Autism Research Initiative (SFARI) and included an innovative reanalysis of dozens of previously published datasets. This is consistent with recent long-term studies in patients with autism centered on microbiome-focused therapeutic interventions. These findings also highlight the importance of longitudinal studies in elucidating the interplay between the microbiome and complex conditions such as autism.

“We were able to reconcile the seemingly disparate data from different studies and find a common language to integrate them. This has allowed us to distinguish between autistic and neurotypical individuals across many studies. We were able to identify the characteristics of ,” said Jamie Morton. Of the corresponding authors of this study, they began the study as postdoctoral fellows at the Simons Foundation and are now independent consultants. “But more importantly, we need robust long-term studies looking at as many datasets as possible and understanding how they change when something changes. is. [therapeutic] intervention. “

The study included 43 authors and brought together leaders in the fields of computational biology, engineering, medicine, autism, and the microbiome from research institutions in North America, South America, Europe, and Asia.

The sheer number of disciplines and specialties in this large-scale collaboration is remarkable and necessary for a coherent and new picture of autism. “

Rob Knight, Director, Center for Microbiome Innovation, University of California, San Diego, Study Co-Author

Autism is inherently complex, and research aimed at pinpointing the specific gut bacteria involved in autism has been confounded by this complexity. First, autism manifests itself in many ways. Individuals with autism are genetically, physiologically, and behaviorally different. Second, the microbiome presents unique challenges. Because microbiome studies typically simply report the relative proportions of specific microbes, sophisticated statistics are required to understand which changes in microbial populations are relevant to the condition of interest. This makes it difficult to find the signal in the noise. To further complicate matters, most of the previous studies were her one-off snapshots of the microbial populations present in people with autism. “The impact of a single point in time is so big that tomorrow and next week can be very different,” said study co-author Brittany Needham, assistant professor of anatomy, cell biology and physiology at the Indiana University School of Medicine. talk.

“We wanted to address the ever-evolving question of how the microbiome is related to autism, so we asked, ‘You can go back to an existing dataset and see how much information you can get from it. Let’s see if it’s possible,’ ”said our co-correspondent. Gaspard Taloncher-Oldenburg, Director of Therapeutics Alliance at New York University, began collaborating with Morton when he was a resident consultant at SFARI.

In the new study, the research team developed an algorithm to reanalyze 25 previously published datasets containing microbiome and other “omics” information. Gene expression, immune system response, diet, etc. – from both autism and neurotypical cohorts. Within each dataset, the algorithm found the best matched pairs of autistic and neurotypical individuals in terms of age and gender. These two factors can typically confound autism research. “We treated each pair as a single data point, rather than comparing mean cohort outcomes within a study, which allowed us to analyze more than 600 of her ASD control pairs for a given age simultaneously. in fact “From a technical standpoint, this required the development of an entirely new computational method,” adds Talonchar-Oldenburg. Their new computational method allowed us to reliably identify microorganisms with different abundances between ASD and neurotypicals. Individual.

To the researchers’ surprise, their analysis identified an autism-specific metabolic pathway associated with specific human gut microbes. Importantly, these pathways were also found elsewhere in autistic individuals, from brain-associated gene expression profiles to diet. “We’ve never seen such a clear overlap between gut microbial metabolic pathways in autism and human metabolic pathways,” says Morton.

Even more surprising is the microbiome associated with autism and a recent long-term fecal microbiota transplant study led by James Adams and Rosa Klazimarnik-Brown of the Biodesign Center for Microbiome Health at Arizona State University. There was overlap with the microorganisms identified in . “We looked at this with different eyes and different lenses to validate our findings,” said Kleimarnik-Brown, who was not involved in the study published today.

“Critical to this study is not only the identification of key indications, but also the computational analysis that identified the need for future research involving long-term, carefully designed measurements and controls that allow for robust interpretation.” said Executive Vice President Kelsey Martin. SFARI and The Simmons Foundation Neuroscience Collaborations were not involved in this study.

“Future studies will require more long-term studies with interventions to clarify causality,” Morton said. Professor Talonchar-Oldenburg cites compliance issues that traditional long-term studies often face, suggesting that study designs may be able to more effectively consider the realities of long-term microbiome sampling in people with autism. . “Practical clinical limitations must be reflected in statistics, which will be reflected in study design,” he says. In addition, long-term studies can provide insights into both groups and individuals, as well as how those individuals respond to specific interventions over time, he said. pointing out.

Importantly, the researchers say these findings extend beyond autism. The approach described here may also be applicable to other areas of biomedicine that have long proven difficult. “In the past, there was smoke indicating that the microbiome was involved in autism, but now there is fire. “It can be applied to many other areas where the microbiome is thought to play a role,” says Knight.