A new review analyzes gut microbiota’s influence on brain development and function in early life

Although gut microbiota maturation is a dynamic process apparent across a lifetime, the first two to three years of life may represent the most critical period for dietary interventions that target the microbiota and its contribution to improving child growth and brain development. One area of current microbiome research studies the close relationship between the development of the gut and the brain in infants and young children.

A new review, led by researchers from University College Cork, University of Groningen, Wageningen University, AMC Amsterdam and Nutricia Research Utrecht and Singapore explores the extent of brain development and function modulation by the gut microbiota in early life.

First, researchers reviewed the parallel development of the brain and gut microbiota from the first few months after birth until 3 years of age. Both early life microbial colonization and brain development share critical periods of vulnerability, in which there is an extensive cross-talk between gut and brain.

During this period of early life, the gut microbiota and the brain develop quickly. Early life microbiota colonization runs in parallel with neuronal migration. Later, the gut colonization during the following two to three years of life coincides with the brain’s critical periods of axonal growth, myelination and synaptic refinement. These physiological changes lead to a stable state for our microbiota and the consolidation of neural networks during toddlerhood, with adequate nutrition being an important factor that influences the development of both the gut microbiota and the brain.

Nowadays, we know that bidirectional communication takes place between the brain and the gut that is modulated by the gut microbiota, allowing for the evolution of the “gut-brain axis” concept to that of the “microbiota-gut-brain axis”. Approaches that have been used to elucidate the gut microbiota’s role in relation to behavior and cognition include the use of germ-free animals, animals exposed to antibiotics, and models of Caesarian section and exposure to maternal stress.

The vast majority of research that has parsed the relationship between the gut microbiota and brain development and function comes from animal models, thus hampering the translation of preclinical findings into humans.

In this context, the preclinical data available indicate that the gut microbiota also communicates with the central nervous system—possibly through neural, endocrine and immune pathways—and thereby influences brain function and behavior. The most widely studied mechanisms by which microbial colonization during early life affects the normal development of the brain include:

  • Regulation of the gut epithelial barrier and blood brain barrier function, gut glial cell homeostasis and microglia maturation,
  • Hormonal and neural regulation via the hypothalamic-pituitary-adrenal axis (HPA axis), and
  • Modulation of immune and metabolic functions (via bacterial metabolites, such as short-chain fatty acids, as well as neurotransmitters, such as glutamate and gamma-aminobutyric acid).

Finally, the researchers also reviewed the impact of nutritional interventions that can shape neurodevelopment by modulating the neonate’s microbiome. There are few preclinical and clinical studies that have explored how diet or specific nutrients affect brain function through the gut microbiome. Of those, the most frequently studied factors that may drive the composition of the infant’s early gut microbiota and subsequent development were maternal diet (during gestation and lactation), early postnatal diet, supplementation with the omega-3 polyunsaturated fatty acids (eicosapentaenoic and docosahexaenoic acids), and prebiotics (human milk oligosaccharides, short-chain galactooligosaccharides, long-chain fructooligosaccharides, and inulin), probiotics and synbiotics supplementation (e.g. Lactobacillus rhamnosus GG and probiotic mixtures).

It should be noted that the use of standardized parameters across studies are urgently needed in order to evaluate the outcomes of the nutritional interventions targeted to protect normal brain development through the gut microbiota. Furthermore, long-term follow-up studies will help elucidate the interaction between the gut microbiota and brain development in early life, which has just begun to be deciphered, mainly through basic research.

On the whole, the gut microbiota’s development during early life parallels critical periods of neurodevelopment. Early life nutrition is therefore an important modifiable factor that can shape both microbiota and brain development. Further clinical research is needed to gain a better picture of interactions between nutrition, gut microbiota and brain development and to produce clear advice on nutrition for improving brain health through the gut microbiota.

 

Reference:

Wang S, Harvey L, Martin R, et al. Targeting the gut microbiota to influence brain development and function in early life. Neurosci Biobehav Res. 2018; 95:191-201. doi: 10.1016/j.neubiorev.2018.09.002.

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GMFH Editing Team
GMFH Editing Team