NEW YORK – A team led by investigators at Wellesley College has tracked down gut microbial community members and microbial gene functions that coincide with neurodevelopment in children, particularly cognitive abilities and brain structure development in youngsters up to 10 years old.
"Understanding the gut-brain-microbiome axis in early life is particularly important, since differences or interventions in early life can have outsized and longer-term consequences than those at later ages due to the dynamic and plastic nature of both the gut microbiome and the brain," the authors explained in a paper published in Science Advances on Friday.
For their study, researchers from Wellesley College, Rhode Island Hospital, and other centers in the US and Norway used shotgun metagenomic sequencing to profile gut microbial features in 493 stool samples from 381 healthy and neurotypical children, ranging from 40-day-old infants to 10-year-olds. They then analyzed these microbiome data alongside results from age-appropriate tests of the children's behavior, cognitive function, early learning, and more, as well as with neuroanatomy features found by magnetic resonance imaging.
"There's been some work in the past looking at connections between the microbiome and atypical brain development (e.g., autism spectrum disorder), and in adult disorders (e.g., depression, neurodegeneration), but to our knowledge, this is the first study looking in depth at typical neurocognitive development in children," first author Kevin Bonham, a researcher at Wellesley College, said in an email.
The team did not see gut microbial taxa with significant ties to cognitive function in children younger than six months old, though Bacteroides fragilis and species in the Streptococcus genus coincided with language-related expression skills in these infants.
On the other hand, in children who were at least 18 months old, the researchers identified not only microbes linked to expressive language but also those that appeared to be associated with cognitive skills. In particular, their machine learning and statistical models highlighted a handful of bacterial species that were overrepresented or diminished in the gut microbial communities of children who scored higher on cognitive tests.
Species such as Alistipes obesi, Asaccharobacter celatus, Eubacterium eligens, and Faecalibacterium prausnitzii turned up at higher levels in the guts of children with higher composite cognitive test scores, for example, whereas gut microbial species such as Ruminococcus gnavus were inversely related to test scores.
Along with microbial taxa associated with brain structure, the analyses revealed a set of gene functions corresponding with brain structure and cognitive performance, including neurotransmitter-producing pathways and pathways involved in short-chain fatty acid production, short-chain fatty acid degradation, and other microbial metabolic processes.
"These findings provide potential biomarkers of neurocognitive development and may enable development of targets for early detection and intervention," the authors wrote, adding that the "discovery of the neuroactive metabolites could provide us with biomarkers for early detection or necessary medicinally useful molecules that can be applied in intervention."
The team's machine learning models also pointed to the possibility of extrapolating from the microbial taxa that were associated with cognition test results to structural changes in brain regions assessed by MRI.
Nevertheless, Bonham noted that "it's too early for clinical implications" since the current findings reflect statistical associations that need to be explored further in terms of causality, particularly in animal models of brain development.