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Gut microbiome of 720 children with autism differs by symptom severity in a Hong Kong sequencing study

Researchers at the Chinese University of Hong Kong compared stool microbiomes of 720 children with ASD and 151 controls. Associations with severity were significant but explained little variance.

Gut microbiome of 720 children with autism differs by symptom severity in a Hong Kong sequencing study
Photo: Ajay Kumar Chaurasiya, Wikimedia Commons, CC BY-SA 4.0 · License: CC BY-SA 4.0

Researchers at the Chinese University of Hong Kong and the Microbiota I-Center (MagIC) performed shotgun metagenomic sequencing of stool samples from 720 children with autism spectrum disorder (ASD) and 151 matched controls. The results were published in Nature Communications. doi.orgNature Communicationsdoi.orgOpen source ↗ The median age of the children with ASD was 8 years, and 87% were male. doi.orgNature Communicationsdoi.orgOpen source ↗

The authors note that earlier work linking the gut microbiome to ASD did not sufficiently account for the clinical heterogeneity of the condition. doi.orgNature Communicationsdoi.orgOpen source ↗ To address this, they divided the children with ASD into three severity groups using 14 symptom subscales. The subscales covered core features of ASD and co-occurring psychopathologies. doi.orgNature Communicationsdoi.orgOpen source ↗

Association with severity

Microbiome composition was significantly associated with clinical severity and with individual symptoms. doi.orgNature Communicationsdoi.orgOpen source ↗ The proportion of microbiome variance explained by these clinical factors was modest, with R2 between 0.0017 and 0.0065. doi.orgNature Communicationsdoi.orgOpen source ↗

In children with higher severity, the abundance of Lachnospiraceae bacterium AM48_27BH, a short-chain fatty acid producer, was reduced. doi.orgNature Communicationsdoi.orgOpen source ↗ The same group showed lower predicted capacity of GABA-related modules: GABA synthesis II, putrescine degradation and GHB degradation. doi.orgNature Communicationsdoi.orgOpen source ↗ NAD+ salvage pathways showed only trend-level associations with severity. doi.orgNature Communicationsdoi.orgOpen source ↗

Sensory atypicalities

Among the symptom domains, sensory atypicalities had the largest number of associated microbial markers. doi.orgNature Communicationsdoi.orgOpen source ↗ They also showed trend-level links to a reduced predicted capacity for degradation of excitatory neurotransmitters. doi.orgNature Communicationsdoi.orgOpen source ↗ According to the authors, different symptom domains differ in their relevance to microbiome alterations. doi.orgNature Communicationsdoi.orgOpen source ↗

The study is observational and compares microbial composition with clinical scores. The authors state that it remains to be tested in mechanistic and longitudinal studies whether alterations in GABAergic metabolism contribute to clinical severity, and whether microbial features are preferentially linked to sensory atypicalities. doi.orgNature Communicationsdoi.orgOpen source ↗ The metabolic capacities described in the paper are predicted from sequencing data, not measured directly. doi.orgNature Communicationsdoi.orgOpen source ↗

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