Rebecca Knickmeyer, PhD, associate professor, Department of Psychiatry, University of North Carolina at Chapel Hill, and colleagues analyzed fecal samples from normally developing 1-year-olds to determine the bacterial composition of their gut.
At age 2 years, some babies scored significantly better on cognitive tests than others. The differences were found to relate to the bacterial clusters that had been identified in the babies' gut microbiomes.
"Ultimately, if we could better understand what in the complex microbiota community are beneficial bacteria for brain development, perhaps those could be given in probiotics and used to support cognitive development," Dr Knickmeyer told Medscape Medical News.
"Of course, that's still quite a way from where we are now, although it's a field that's moving fast," she added.
The study was published in Biological Psychiatry.
"The first year of life is the foundational period for microbial colonization of the gut and the most rapid and dynamic phase of postnatal brain development," the authors write.
The possible concurrence of these processes has not been empirically tested in human beings, although studies in rodent models "provide compelling evidence that microorganisms inhabiting the gut influence neurodevelopment," particularly "exploratory and communicative behaviors and cognitive performance."
"A number of replicated studies in animal research showed that if you manipulated the microbiome, you could affect behavior," Dr Knickmeyer said.
"We wanted to look at the early foundational period, when the microbiome is being set up, because, although brain development occurs throughout the lifespan, the first 2 years show very rapid and dynamic growth, including the setting up of functional brain networks and myelination," she recounted.
The researchers hypothesized that gut microbiome samples would cluster into groups of "community similarity" and that children with different clusters would differ in cognitive ability.
They predicted that overall cognitive performance would be highest in clusters with an abundance of putatively beneficial microorganisms (eg,
Lactobacillus or Bacteroides) and that lower alpha diversity (signifying a less mature microbiome) would be correlated with lower cognitive performance.
To investigate the question, the researchers studied fecal material of 1-year-old infants (n = 89) from two prospective, longitudinal studies of early brain development.
At age 2 years, the children's cognitive abilities were assessed using the Mullen Scales of Early Learning and the Early Learning (Cognitive) Composite (ELC). The Mullen Scales of Early Learning consists of five scales that measure gross motor, fine motor, visual reception, expressive language, and receptive language skills.
In addition to cognitive testing, brain images were obtained during unsedated natural sleep (median age at first scan, 12.8 months; median age at second scan, 25.1 months).
The scans provided information about measures of intracranial volume, total gray matter, total white matter, total cerebrospinal fluid, lateral ventricle volume, and 90-region gray matter volumes.
Slower Maturation Better
The babies were found to cluster into three groups: Cluster 1 (C1) was characterized by a relatively high abundance of Faecalibacterium, cluster 2 (C2) by a relatively high abundance of Bacteroides, and cluster 3 (C3) by a relatively high abundance of an unnamed genus in the family Ruminococcaceae.
After false discovery rate (FDR) correction, breastfeeding at time of sample collection (1 year), birth method, and paternal ethnicity were significantly different between clusters. Infants in C2 were more likely to be breastfed at age 1 year and were less likely to have been born via cesarean delivery.
Paternal ethnicity in C2 was 90% white; in C3, paternal ethnicity was 71% white; in and C1, paternal ethnicity was 57% white.
The primary analysis showed that the children's cognitive abilities differed between clusters. At age 2 years (n = 69), C2 showed the highest performance on ELC scores, and C1 showed the lowest performance (P = .006).
No significant differences were observed in Mullen Scales outcomes between clusters at 1 year (n = 86).
At age 2, higher alpha diversity was associated with lower Mullen scores on the overall composite score, the visual reception scale, and the expressive language scales. C1 showed the greatest alpha diversity, and C2 showed the least.
Although there were some differences between the three clusters on neuroimaging data, exploratory analyses revealed that the gut microbiome had "minimal effects" on regional brain volumes at 1 and 2 years of age.
"This is the first study to show that variation in the human gut microbiome is associated with cognition in a cohort of typically developing infants during the hypothesized period of sensitivity," the authors write.
They suggest that C2, which had increased levels of Bacteriodes, may reflect a subgroup of children with delayed maturation of the gut microbiome, because these bacteria are subsequently displaced during development by diverse mixtures of Clostridiales, including the bacteria found in C1 and C3 (Faecalibacterium and Ruminococcaceae species, respectively).
"It is possible, although this is speculative, that maturing the microbiome faster in this sample may be less beneficial, or that slower development of the microbiome is related to more extended period of brain plasticity," Dr Knickmeyer suggested.
"We also expected to find that children with more diverse microbiota would have better cognitive development, but we saw the reverse and are still thinking about why that might be, since higher diversity is usually considered good because it typically creates a more stable functional community," she recounted.
"Possible explanations are that the diverse community might contain pathogenic bacteria with potentially negative effects on brain development, or that in a diverse community, all the bacteria have to share resources, so fewer resources go to the beneficial bacteria."
Encourage Breastfeeding, Vaginal Delivery
Commenting on the findings for Medscape Medical News, Brett B. Finlay, PhD, OC, OBC, Peter Wall Distinguished Professor and CIFAR senior fellow, Michael Smith Laboratories, University of British Columbia, Vancouver, Canada, who was not involved with the study, called the findings "exciting and preliminary."
Most "researchers in the field believe that in animal models, early life microbiome does affect brain development, and I think this is the first study in humans hinting at this," he said.
He cautioned that, as the authors note, "it is only a correlative study, and no conclusions can be drawn to causation and microbiome."
Additionally, "at 1 year of age, when the sample was taken, solid foods are being introduced, and there is much variation over time, so a longitudinal study is needed."
Timothy Dinan MD, PhD, professor of psychiatry and principal investigator, APC Microbiome Institute, University College Cork, Ireland, who also was not involved with the study, agreed that a "major limitation is the fact that the microbiota was not assessed serially at multiple time points."
Nevertheless, the study "strongly links initial gut microbiota to subsequent cognitive development," he told Medscape Medical News.
Dr Dinan, who is the coauthor of an accompanying commentary, emphasized that the study has a take-home message.
"Factors that determine the initial microbiota, such as breast vs bottle, can impact cognitive functioning."
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Dr Knickmeyer agreed. "Although it is too soon to say that people should use a specific probiotic or adopt a specific diet, our research matches up in showing that breastfeeding is good and vaginal delivery can have positive effects."
This study was supported by National Institute of and the Foundation of Hope for Research and Treatment of Mental Illness. The work of Dr Dinan and coauthors is supported by the Alimentary Pharmabiotic Center from Science Foundation Ireland, the Health Research Board of Ireland, and the European Community's Seventh Framework Programme Grant MyNewGut. Dr Knickmeyer is a coinvestigator on a grant from Nestle/Wyeth. The other authors have disclosed no relevant financial relationships.