A new study, published in the peer-reviewed journal Science Advances, is shedding light on the potential link between autism and gut microbiome impairments. The research reveals a mechanism by which altered gut bacteria populations can lead to abnormal microbial detoxification and mitochondrial dysfunction.
The connection between gut bacteria and autism spectrum disorder (ASD) is arguably one of the most intriguing areas of microbiome research. Gastrointestinal problems are common in children with ASD and several recent, albeit small, studies have revealed behavioral and psychological symptoms of autism in children can be improved using fecal transplants from healthy subjects.
Perhaps the most challenging hurdle microbiome researchers face translating their discoveries into clinical therapies is the sheer, mind-bending diversity of gut bacteria populations from individual to individual. Put simply, while some bacterial species can be generally considered "good" and others "bad", there is no one-size-fits-all solution to microbiome therapeutics. And it is this diversity that makes it hard for researchers to home in on exactly how the microbiome influences disease.
Trying to overcome this hurdle, a large team of scientists from China developed a novel analytic strategy called a “quasi-paired cohort.” First, the researchers enrolled a traditional cohort of 79 age- and gender-matched children, half with ASD and half serving as neurotypical controls.
Initial microbiome genomic testing revealed little differences in bacterial diversity between the two groups. A small handful of differences were identified between the two groups, but these were generally in line with what had been identified in previous research.
The next step was to generate a quasi-paired cohort. This involved pairing specific ASD samples with control samples of similar metabolic backgrounds. As the researchers explain in the study, “This approach allowed us to transform the original group cohort into a paired cohort, which not only controls for individual diversity but also increases statistical power.”
This allowed the researchers to identify more than just simple differences in bacterial populations, but instead revealed the key downstream metabolic differences between ASD and neurotypical subjects.
Five specific metabolic pathway deficiencies were detected in the research. These deficiencies were linked to detoxification processes triggered by certain enzymes produced by gut bacteria. The researchers hypothesize these microbiome detoxification deficiencies influence the pathogenesis of ASD.
“One of the main pathological manifestations of ASD is the dysfunction in mitochondria, major targets of organic toxicants due to their lipophilic properties,” the researchers write in the study. “When the intestinal microbial detoxification is severely impaired in ASD, more toxicants of external and internal origins might enter circulation and injure the mitochondria of various tissues. Thus, our finding of impaired microbial detoxification helps explain why ASD children are so vulnerable to environmental toxins and suggests that impairment in microbial detoxification might be involved in the pathogenesis of ASD.”
As with most research on this subject, there are plenty of caveats limiting broader conclusions. While the study does offer a rigorous investigation showing ASD subjects may present a deficiency in microbiome detoxification pathways, any causal link to ASD onset or severity is just speculation at this stage. Further research is needed to both affirm this connection and investigate whether modulating the microbiome can prevent ASD developing in the first place.
“The impaired microbial detoxification is correlated with the clinical rating of ASD and the extent of mitochondrial dysfunction, one of the main pathological alterations of ASD, which strongly suggests that impaired microbial detoxification is deeply involved in the pathogenesis of ASD,” the researchers conclude in the study. “Such a previously unknown protective role of intestinal microbes suggests potential future therapeutic strategies of rebuilding the impaired microbial detoxification for patients with ASD.”
The new study was published in the journal Science Advances.
