by Bianca Garilli, ND
During the first years of life, an infant’s gut microbiota undergoes rapid colonization, and the microbial diversity of the growing infant results from exposure to a variety of sources.1 These microbiota sources are impacted by a variety of factors, including but not limited to: genetic underpinnings, the mother’s microbiota composition, method of delivery (vaginal vs. cesarean section), hospital and birthing environment, feeding sources (breast vs. bottle), sanitation of environments exposed to, and antibiotic use.1 By 2-5 years of age, a child’s gut microbiota closely resembles that of an adult in terms of composition and diversity and develops a unique microbiome fingerprint.1 Studies suggest that this early life gut bacterial population will set the stage for influencing health and development throughout the child’s life.1
The first years of a child’s life are a critical period for brain development, when the growth, myelination and maturation of neural networks occurs rapidly and dynamically.2 Substantial intestinal development also occurs during this period, and emerging research in animal models suggests that the early life gut microbiome may influence aspects of brain development and behavior.2-3 Therefore, it is conceivable that supporting a healthy gut microbiota composition during the first years of life may impact cognitive development and function.
A recent study in Biological Psychiatry conducted by a team of researchers from The University of North Carolina, Chapel Hill aimed to better understand how differences in gut microbial composition and diversity in infants may be associated with neurodevelopmental and cognitive performance measures.4 Researchers gathered fecal samples from 89 infants aged 1 year and isolated the bacterial DNA for sequencing and identification of the fecal microbiome. At 1 and 2 years of age, global and regional brain volumes were obtained by MRI conducted during unsedated natural sleep, and cognitive development was assessed at 2 years of age by the Mullen Scales of Early Learning.4
The researchers sorted the children into 3 distinct categories (C1, C2, C3) differentiated by the fecal bacterial composition, which was clustered based on an algorithm using the relative abundance of the bacterial genera. An inverse association between cognitive performance and bacterial diversity was observed: the infants whose stool samples contained a higher alpha diversity at 1 year of age (higher alpha diversity indicates a high number of different species at relatively similar levels of abundance present in the sample)5 had lower cognitive development scores, both for the Mullen composite scores, as well as for the 2 of the 5 subdomains (visual receptions and expressive language scale).4 This was perhaps a surprising finding, since high alpha diversity is considered a more “mature” microbial composition and has been associated with healthy adults.2
Bacterial clusters (C1, C2, C3) at 1 year of age were associated with cognitive performance at 2 years of age. Specifically:4
- C2 group: (high levels of Bacteroides) lowest alpha diversity was associated with better cognitive performance (90th percentile). C2 infants were more likely to be birthed vaginally and be breastfed, and are considered to have a less mature microbiome
- C1 group: (high levels of Faecalibacterium) highest alpha diversity was associated with poorer cognitive performance (72nd percentile)
- C2 > C3 > C1 was the cluster pattern observed for the visual reception scale
A high alpha diversity is thought to indicate a more mature, adult-like community, but the concept of high vs. low alpha diversity being positive vs. negative is certainly still an active area of debate and ongoing research. This is the first study to demonstrate an association between the human gut microbiota and cognitive outcomes in developing infants.4 Importantly, a causal link between human gut microbial development and neurodevelopment has not been demonstrated here, and further the majority of studies to date in this area have been conducted in animals.4
Future studies would benefit from incorporating multiple measurement time points for microbiota sampling and longer follow-up duration. Additionally, incorporating data on broad-spectrum metabolomics or transcriptomics may suggest mechanistic insights.4 This future research is critical to understand the associations between gut bacterial composition in infants and long-term neurodevelopment and cognitive health, so that targeted interventions can be informed for future investigations.
Why is this Clinically Relevant?
- Various routes of exposure in the antenatal and postnatal period of life influence the long-term, individualized microbiota signature
- It is important to establish a healthy gut microbiota in the newborn and developing infant via:
- Exposure to maternal vaginal microbiota during delivery if possible
- Limiting antibiotic use in early years
- Breastfeeding and maternal skin to skin contact in early months of life6
- The gut microbiota diversity in infants was recently associated with measures of cognitive performance in the growing infant4
- Further research will be important to understand this association further, potentially leading to targeted microbiota interventions to support healthy neurodevelopmental outcomes in children
- Rodriguez JM, Murphy K, Stanton C, et al. The composition of the gut microbiota throughout life, with an emphasis on early life. Microb Ecol Health Dis. 2015;26:26050.
- Sharon G, Sampson TR, Geschwind DH, Mazmanian SK. The Central Nervous System and the Gut Microbiome. Cell. 2016;167(4):915-932.
- Sampson TR, Mazmanian SK. Control of brain development, function, and behavior by the microbiome. Cell Host & Microbe. 2015;17(5):565-576.
- Carlson A, Xia K, Azcarate-Peril MA, et al. Infant gut microbiome associated with cognitive development. Biological Psychiatry. 2018;83(2):148–159.
- Research Gate. https://www.researchgate.net/post/What_is_the_difference_between_alpha-diversity_and_beta-diversity_in_microbial_ecology. Accessed February 17, 2018.
- Rautava S, Luoto R, Salminen S, Isolauri E. Microbial contact during pregnancy, intestinal colonization and human disease. Nat Rev Gastroenterol Hepatol. 2012;9(1):565-576.