Groundbreaking study unlocks the connection between autism and gut health
[July 9, 2023: Staff Writer, The Brighter Side of News]
Autism has persistently stymied the scientific community for years, with its complex biological origins baffling the relentless search for answers. (CREDIT: Creative Commons)
Autism has persistently stymied the scientific community for years, with its complex biological origins baffling the relentless search for answers. While the labyrinth of genetic, cellular and microbial factors that contribute to the condition is broadening, it still remains largely unchartered.
However, a new area of research focus—the microbiome—has been catching the attention of scientists worldwide. A ground-breaking study, published in the revered journal, Nature Neuroscience, promises to unlock the puzzling relationship between the human gut microbiome and autism.
This captivating research originates from the Simons Foundation's Autism Research Initiative (SFARI) and sheds new light on the connection through an innovative computational approach.
By analyzing numerous previously published datasets, the study resonates with the findings of a long-term study on individuals with autism that focused on microbiome-centered treatment intervention. It also emphasizes the critical role of longitudinal studies in understanding the intricate interplay between the microbiome and complex conditions, such as autism.
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Jamie Morton, one of the leading authors of the study and now an independent consultant, who initiated this work during his tenure as a postdoctoral researcher at Simons Foundation, observed, “We were able to harmonize seemingly disparate data from different studies and find a common language with which to unite them. With this, we were able to identify a microbial signature that distinguishes autistic from neurotypical individuals across many studies.”
His statement encapsulates the pivotal aspect of the research. However, he is quick to stress the need for future investigation. “But the bigger point is that going forward, we need robust long-term studies that look at as many datasets as possible and understand how they change when there is a [therapeutic] intervention,” he states.
This colossal undertaking involved 43 authors from institutions spread across North America, South America, Europe, and Asia. They brought together a unique mix of expertise in computational biology, engineering, medicine, autism, and microbiome research.
Diagram delineating the concept of age matching and sex matching. (CREDIT: Nature Neuroscience)
Rob Knight, director of the Center for Microbiome Innovation at the University of California San Diego and a co-author of the study, believes in the power of collaboration. “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,” he emphasizes.
Untangling the knot that is autism involves addressing its inherent complexity. Previous attempts to identify specific gut microbes involved in the condition have been confounded by the heterogeneous nature of both autism and the microbiome. With autistic individuals differing from each other genetically, physiologically, and behaviorally, and the unique challenges presented by the microbiome, pinpointing relevant microbial population changes has proven difficult.
Brittany Needham, study co-author and assistant professor of anatomy, cell biology and physiology at the Indiana University School of Medicine, remarks, “A single time point is only so powerful; it could be very different tomorrow or next week.” She is referring to the fact that most studies to date have been single snapshots of the microbial populations present in autistic individuals.
Differential ranking analysis across omics levels. (CREDIT: Nature Neuroscience)
Co-corresponding author Gaspar Taroncher-Oldenburg, director of Therapeutics Alliances at New York University, who initiated the work with Morton while he was a consultant-in-residence for SFARI, was eager to tackle the ever-evolving question of the microbiome's association with autism. He explains, “We wanted to address the constantly evolving question of how the microbiome is associated with autism, and thought, ‘let's go back to existing datasets and see how much information we may be able to get out of them.’”
In their research, the team developed a novel algorithm to re-analyze 25 previously published datasets. These datasets contained "omic" information such as gene expression, immune system response, and diet, in addition to microbiome data from both autistic and neurotypical cohorts. By treating each matched pair of autistic and neurotypical individuals in terms of age and sex as a single data point, they simultaneously analyzed over 600 ASD-control pairs.
“Rather than comparing average cohort results within studies, we treated each pair as a single data point, and thus were able to simultaneously analyze over 600 ASD-control pairs corresponding to a de facto cohort of over 1,200 children,” Taroncher-Oldenburg explains, acknowledging the development of novel computational methodologies as a crucial technical standpoint of the study. Their new computational approach enabled them to reliably identify microbes that have differing abundances between ASD and neurotypical individuals.
Unsurprisingly, the research team made an astonishing discovery. Their analysis identified autism-specific metabolic pathways linked to certain gut microbes. Furthermore, these pathways were seen in other aspects of autistic individuals, from their brain-associated gene expression profiles to their diets. A visibly pleased Morton notes, “We hadn’t seen this kind of clear overlap between gut microbial and human metabolic pathways in autism before.”
One of the most startling findings was the overlap between microbes associated with autism, and those identified in a recent long-term fecal microbiota transplant study led by James Adams and Rosa Krajmalnik-Brown at Arizona State University's Biodesign Center for Health Through Microbiomes. Krajmalnik-Brown, who was not involved in the current study, was excited by the validation. “Another set of eyes looked at this, from a different lens, and they validated our findings,” she says.
Notably, Kelsey Martin, executive vice president of SFARI and the Simons Foundation Neuroscience Collaborations, who was not involved in the study, lauds the computational analysis. “What’s significant about this work is not only the identification of major signatures, but also the computational analysis that identified the need for future studies to include longitudinal, carefully designed measurements and controls to enable robust interpretation,” she notes.
Echoing this sentiment, both Morton and Taroncher-Oldenburg stressed the need for more longitudinal studies involving interventions. They argue that these will enable a better understanding of cause and effect. Taroncher-Oldenburg, who mentions the compliance issues that plague traditional long-term studies, suggests that the practicalities of long-term microbiome sampling of autistic individuals should guide study designs. “Practical, clinical restrictions must inform the statistics, and that will inform the study design,” he asserts.
Characterizing the associations among differentially abundant microbes in ASD and cytokines, gene expression in the brain and dietary patterns. (CREDIT: Nature Neuroscience)
Significantly, the researchers insist that these findings have implications that go far beyond autism. They believe that their approach can be employed in other areas of biomedicine that have proven challenging. Knight, summing up the broader potential of their work, says, “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, from depression to Parkinson’s to cancer, where we think the microbiome plays a role, but where we don’t yet know exactly what the role is.”
Indeed, this breakthrough study signifies a giant leap for research on autism and the human microbiome. It not only highlights the potential of computational biology in biomedical research but also underscores the importance of international collaboration. As the scientific world strives to better understand the enigma that is autism, this research offers a valuable new perspective that could be instrumental in developing future therapies.
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