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Gut Microbiome Analysis in Autistic Children Points to Detoxification Deficiencies

NEW YORK – New research suggests children with autism spectrum disorder (ASD) may have altered gut microbial community functions that impact the detoxification processes taking place in the intestine — changes that appear to have downstream effects on mitochondrial function.

"[O]ur study revealed a previously unidentified ASD-associated deficiency in microbial detoxification, which exhibited a strong correlation with the degree of mitochondrial dysfunction, as well as the severity of clinical ASD manifestations," co-senior authors Juan Wang, a researcher at Peking University and the university's Health Science Center, and Yu Kang, an investigator at the Chinese Academy of Sciences, and their colleagues wrote in Science Advances on Wednesday.

The researchers assessed metagenomic sequence data from dozens of three- to eight-year-old children with or without ASD using a so-called quasi-paired cohort analytical approach. This strategy — which involved direct comparisons between sex- and age-matched ASD cases and controls with comparable microbiome metabolic backgrounds based on metagenomic data — pointed to declining detoxifying enzyme levels in gut samples from children with the neurodevelopmental condition.

Through a series of follow-up experiments, including urine metabolite analyses, the team tracked down related metabolic changes in individuals with ASD, such as urine metabolite shifts that appeared to correspond with mitochondrial damage or dysfunction.

"[O]ur results suggest a previously undiscovered potential role of impaired intestinal microbial detoxification in toxin accumulation and mitochondrial dysfunction, a core component of ASD pathogenesis," the authors reported, adding that the results may "pave the way for designing future therapeutic strategies to restore microbial detoxification capabilities for patients with ASD."

For their study, the researchers considered metagenomic sequence data generated using stool samples from 39 children with ASD and 40 unaffected controls matched for age, biological sex, and microbial alpha diversity — a measure of microbial species richness and diversity — in the gut. Based on profiles involving more than 200 microbial species found across these samples, they focused on 18 species with distinct representation in the ASD cases and controls.

When the team dug into the microbiome differences with an expanded quasi-paired cohort analysis involving 65 children with ASD and as many without, it saw shifts in the proportion of detoxifying enzymes and alterations affecting five related pathways in microbiomes from ASD-affected children, among other changes.

From these and other results, the authors speculated that the altered gut microbe detoxification features and mitochondrial function changes may offer new insights into the sensitivity to environmental toxins that have been proposed for some children with ASD in the past.

"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," they suggested, noting that their study "helps to 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."

The researchers cautioned that additional research is needed to dig into the potential genetic and environmental contributors to the microbial detoxification differences detected with their metagenomic sequence data.

Still, they noted, the results point to a "previously unknown protective role of intestinal microbes" and hint at the possibility of coming up with therapeutic candidates that can boost or rebuild the detoxification capabilities of microbes in the gut.

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