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Microbiome and its impact on fetal and neonatal brain development: current opinion in pediatrics
Nina M Frerichs1,2, Tim G J de Meij1,2, Hendrik J Niemarkt3,4
1Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism Research Institute, Department of Pediatric Gastroenterology, Emma Children's Hospital Amsterdam, The Netherlands.
Insights
The gut microbiota influences brain development through the microbiota-gut-brain axis. Early microbial signatures are linked to neurodevelopmental outcomes, suggesting potential for microbiota-based interventions.
Area of Science:
- Neuroscience
- Microbiology
- Developmental Biology
Background:
- The microbiota-gut-brain axis (MGBA) is a bi-directional communication system where gut microbes and their metabolites impact neurodevelopment and cognition.
- The MGBA involves pathways like the hypothalamic-pituitary axis, vagal nerve, immune signaling, and microbial metabolites (e.g., SCFAs, tryptophan derivatives, bile acids).
Approach:
- Animal studies demonstrate maternal microbiota influence on fetal neurodevelopment and that microbiota manipulation (antibiotics, FMT) affects cognitive function.
- Human studies, especially in preterm infants, indicate disrupted gut microbiota colonization may adversely impact neurodevelopment.
- Early microbial signatures have been associated with both positive and negative neurodevelopmental outcomes.
Key Points:
- The gut microbiota plays a significant role in regulating neurodevelopment and cognitive functions.
- Mechanisms include hormonal, neural, immune, and metabolic signaling pathways.
- Early life microbial colonization is critical and can be predictive of neurodevelopmental trajectories.
Conclusions:
- The connection between gut microbiota and brain function is well-established.
- Further research, including longitudinal studies and RCTs, is needed to fully understand MGBA mechanisms.
- Identifying early microbial markers could enable targeted interventions like probiotics or microbiota transplantation to enhance infant neurodevelopment.
Purpose Of Review:
Emerging evidence suggests that the gut microbiota and its metabolites regulate neurodevelopment and cognitive functioning via a bi-directional communication system known as the microbiota-gut-brain axis (MGBA).
Recent Findings:
The MGBA influences brain development and function via the hypothalamic-pituitary axis, the vagal nerve, immune signaling, bacterial production of neurotransmitters, and microbial metabolites like short-chain fatty acids, tryptophan derivatives, and bile acids. Animal studies show fetal neurodevelopment is mediated by maternal microbiota derivatives, immune activation, and diet. Furthermore, manipulation of the microbiota during critical windows of development, like antibiotic exposure and fecal microbiota transplantation, can affect cognitive functioning and behavior in mice. Evidence from human studies, particularly in preterm infants, also suggests that a disrupted gut microbiota colonization may negatively affect neurodevelopment. Early microbial signatures were linked to favorable and adverse neurodevelopmental outcomes.
Summary:
The link between the gut microbiota and the brain is evident. Future studies, including experimental studies, larger participant cohort studies with longitudinal analyses of microbes, their metabolites, and neurotransmitters, and randomized controlled trials are warranted to further elucidate the mechanisms of the MGBA. Identification of early, predictive microbial markers could pave the way for the development of novel early microbiota-based intervention strategies, such as targeted probiotics, and vaginal or fecal microbiota transplantation, aimed at improving infant neurodevelopment.
