Identify possible biomarkers in intestinal microbiota for diagnosing autism


Researchers from Hong Kong have found 31 microbial markers that allow distinguishing children with autism spectrum disorder from neurotypical children

Microorganisms present in a gut microbiota analysis.
Microorganisms present in a gut microbiota analysis.SHUTTERSTOCK

Autism spectrum disorders (ASD) are still surrounded by uncertainties. The causes, related mechanisms, and associated bodily changes are not yet fully understood. It is considered that multiple factors, both genetic and environmental, play a role in its development, and their interrelation is under investigation.

One area of study in recent years has focused on the role of the intestinal microbiota due to the known function of these microorganisms with which we coexist in the gut-brain axis. Several studies had indicated the presence of altered intestinal microbiota in children with autism spectrum disorders. However, on Monday, a study led by scientists from the Chinese University of Hong Kong took a step further in this association by identifying a panel of 31 microbial biomarkers that could be used for diagnosing this condition. The details of the study are published in the latest issue of the journal Nature Microbiology.

Unlike previous studies, this research not only focused on the bacteria that make up the intestinal microbiota but also shed light on other microbial kingdoms that are part of this universe of microorganisms living in our gut, such as viruses, fungi, or archaea, as well as their metabolism and functional pathways.

The team led by Qi Su conducted metagenomic sequencing of fecal samples from 1,627 children aged between one and 13 years (24.4% of whom were girls) from five different cohorts in China. Some of the samples had some form of autism spectrum disorder, while the rest exhibited neurotypical development.

After accounting for potential confounding factors such as diet, medication, or health problems, the scientists identified 14 archaea, 51 bacteria, 7 fungi, 18 viruses, 27 microbial genes, and 12 altered metabolic pathways in children with ASD.

Using artificial intelligence tools, the scientists created a panel of 31 biomarkers that demonstrated a high diagnostic capacity to differentiate children with ASD. In their conclusions, the researchers suggest that this panel could have significant potential for clinical use, as its effectiveness was confirmed in different cohorts.


According to Sonia Villapol, a neuroscientist at the Houston Methodist Research Institute (Texas, USA), the identified panel represents a "potentially promising non-invasive tool for diagnosing ASD."

"This is the path and trend for conducting personalized diagnoses, establishing more precise diagnostic profiles. The future of diagnostic and therapeutic medicine should follow these guidelines," Villapol points out, whose main research area revolves around the connection between the gut and the brain through the microbiota.

Although previous studies had "demonstrated the association between microbiome alterations (dysbiosis) and manifestations of ASD" and "numerous clinical trials indicate that probiotic supplementation can have positive effects on specific symptoms in individuals with ASD, including gastrointestinal problems, depression, and anxiety," for the first time in this article published in Nature Microbiology, "metagenomic studies are conducted allowing the analysis of more than just bacteria, also including archaea, fungi, viral species, and functional pathways of the microbiome," which has enabled the establishment of "diagnostic and predictive panels for ASD."

"This study provides evidence that intestinal microbiota profiles from multiple kingdoms could serve as promising biomarkers for diagnosing autism spectrum disorders. These findings open new perspectives for the development of non-invasive diagnostic tools based on intestinal microbiota for ASD," agrees Antonio Pineda-Lucena, scientific director of the Cima University of Navarra and a researcher specialized in the relationship between microbiota and various pathologies.

"The observed differences in the intestinal microbiota of individuals with ASD appear to be related to alterations in microbial metabolism, microbiota-immune system interactions, the production of neuroactive metabolites, and communication through the gut-brain axis," he points out. "These mechanisms may be influenced by genetic and environmental factors," he emphasizes.

Despite the importance of the research, Pineda-Lucena and Villapol agree that the study has limitations that need to be considered.

For example, it is challenging to establish "corrections in integrating these markers with other environmental, demographic, dietary factors, etc., as there are no previous analyses validating these estimates, and perhaps before this panel is approved as a diagnostic tool, "more extensive studies should be repeated," Villapol notes. She also recalls that "this article used machine learning tools to make corrections with dietary factors in the analysis to rule out this influence as a determinant, but it was not done with genetic factors since we are unaware of the interaction of the microbiota with genetics, or even with epigenetic changes."

Regarding the possibility of opening a therapeutic pathway through this line of study, Pineda-Lucena points out that the findings are "encouraging and open new perspectives for the development of therapies based on modulating the microbiome in autism spectrum disorder." However, while "the therapeutic use of intestinal microbiota in ASD is a promising strategy, it is still in an early stage of research. More scientific evidence is required through broader and more rigorous studies to assess its true potential and clinical viability," the researcher emphasizes.

Meanwhile, Toni Gabaldón, ICREA research professor and head of the Comparative Genomics group at the Institute for Research in Biomedicine (IRB Barcelona) and the Barcelona Supercomputing Centre (BSC-CNS), has stated in comments to SMC Spain that "the study uses appropriate methodology and quality data. It is noteworthy for the high number of samples and their good characterization in terms of diet and lifestyle factors, which greatly influence the intestinal microbiome. They also make the effort to recruit complementary cohorts and reanalyze public data to assess the robustness of their results."

"It has been known for some time that children with autism spectrum disorder have a different intestinal microbiota, but most studies are based on the analysis of the bacterial component and taxonomic composition. Using shotgun methodologies, where all the DNA of the sample is sequenced and not just marker genes, this study provides a more comprehensive view, observing changes in archaea, fungi, and viruses, and providing insight into potential metabolic changes associated with microbiota changes. It also has a very particular focus on discovering biomarkers and proposes a panel of 31 species that discriminate quite well," the researcher points out, while emphasizing that "as always, it must be remembered that correlation studies need to be confirmed with more targeted studies to determine if any cause-effect relationship can be established."

"The study identifies some metabolic pathways involved in neurotransmitter synthesis, which establishes an interesting hypothesis about a possible functional relationship that should be established in future studies. Computational predictors trained on data need to be tested in other situations and with new datasets since they often work very well in similar contexts to those they were trained on but may fail in other situations."

"Current diagnosis is based on behavioral patterns that emerge over time; adopting early biomarkers that could help detect autism sooner could facilitate the initiation of earlier therapies. If there are metabolic changes that influence the progression of symptoms and could be compensated for through diets or the use of probiotics, modulating the microbiota would open the door to new treatments that improve some aspects," he concludes.