Progressive Early Dysregulation of Gut Microbiota Associated With Autism Spectrum Disorder

Study data published in Gut identified progressive deviations in the development of gut microbiota in children with autism spectrum disorder (ASD). Compared with neurotypical children, patients with ASD displayed early unsustainable and immature microbiota, decreased alpha diversity, and difficulties or obstructions in the colonization of early key bacterial groups. These data point towards the gut as playing a key role in the pathogenesis of ASD.

This prospective observational study enrolled patients with clinically diagnosed ASD aged 16 months to 19 years from 25 provinces in China. A control cohort of neurotypical children was assembled from 14 of the same study sites. Stool samples were collected from each participant and processed for 16S rRNA gene sequencing.

The 30 most abundant taxa in both the ASD and neurotypical groups were used to “map” the developmental spectrum of gut microbiota. Microbiome alterations between patients and control participants were assessed using profile monitoring for microbial relationship alteration (PM2RA). ASD symptom severity was extracted from medical records; the potential impact of microbiome alterations on clinical presentation was examined using PM2RA. Models were adjusted for host covariates known to affect the gut microbiota, including age, sex, region of residence, diet, clinical comorbidities, and perinatal factors.

The study cohort included 773 patients with clinically diagnosed ASD and 429 neurotypical control participants. A clinical diagnosis of ASD had a profound impact on the diversity and abundance of certain taxa. The alpha diversity in the ASD group was significantly reduced compared with the neurotypical cohort. The incidence rates of clinical comorbidities were elevated in the ASD group compared with the control group — particularly gastrointestinal comorbidities (63.9% vs 10.7%). Children with both ASD and gastrointestinal complications showed significant differential relative abundance of 12 genera compared against children with ASD only.

In analyses which assessed changes in abundance over time, alpha diversity in the neurotypical group increased rapidly over the first 2 to 3 years of life, then entered a period of stability. Children in the ASD group, however, displayed early unsustainable immature microbiota and altered microbial relationships both within and after the first 3 years of life. The degree of alterations was associated with ASD symptom severity and the likelihood of sleep and gastrointestinal problems.

In area under the receiver operating characteristic curve (AUC) analyses, children with ASD could be effectively differentiated from neurotypical children by differences in 2 operational taxonomic units (Veillonella and Enterobacteriaceae) and 17 microbial metabolic functions (AUC, 0.86).

Results from this study highlight the regulatory effect of the gut microbiota in ASD. Early alterations in the microbiome were associated with ASD symptoms, sleep disruptions, and gastrointestinal problems, suggesting that gut analyses may be a key early sign of ASD and associated comorbidities. Future research is necessary to confirm findings from this analysis.

“[T]he progressive deviation in the development of gut microbiota of subjects with ASD highlighted the influence of age on the composition of gut microbiota,” investigators wrote. “In the future, by constructing longitudinal cohorts of children with ASD and [neurotypical children], and integrating metagenomics and metabolomics analyses, we can precisely identify potential developmental windows during which the gut microbiota may be particularly sensitive to ASD development, and further provide critical clues to reveal how gut microbiota participates in the pathogenesis of autism by regulating metabolic pathways.”

Reference

Lou M, Cao A, Jin C, et al. Deviated and early unsustainable stunted development of gut microbiota in children with autism spectrum disorder. Gut. Published online December 20, 2021. doi: 10.1136/gutjnl-2021-325115