Gut Microbiota Plays a Role in Brain Growth

Massive Bioinformatics


Home to trillions of bacteria and thousands of species, the gut microbiota can influence human physiology in a variety of ways. As humans, our gut microbiota begins to form during our mothers’ pregnancy. Together, the genome of all these microorganisms represents the gut microbiome. Microbiota development and colonization accompany brain development during pregnancy and for several years after birth. A dysregulation of the gut microbiome can affect maturation processes, particularly neuronal development and glial development. Thus, a dysregulated gut microbiome can lead to atypical brain development through immune system disruption. A balanced microbiome is necessary to prevent neurodevelopmental psychiatric disorders. These disorders include attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD) and schizophrenia (Schizophrenia), affecting children in early adolescence and later in life in their daily lives.

During the in-utero and postnatal periods, the gut microbiome is one of the important players in the brain development process by actively influencing neuron development and maturation. During the period from the womb to 3 years of age, both the microbiota between individuals and the individual’s own microbiota are the most variable. In addition, the foundations of the immune system are laid during this period, so individuals are most vulnerable to complications that may arise from external factors. According to studies, gut microbes play an active role in neurodevelopmental processes, including blood brain barrier formation, neurogenesis, microglia maturation and myelination. These processes are critical in shaping animal behavior and cognition.

Blood Brain Barrier

The blood brain barrier, composed of capillary endothelial cells sealed by tight junction proteins, pericytes and astrocytes that form the restrictive barrier between the brain and the systemic circulation, is formed in early in-utero. It also facilitates the exchange of molecules and nutrients for the proper functioning of the brain. The presence of a balanced gut microbiota and microbial-derived metabolites is essential in regulating the formation and maintenance of an intact blood brain barrier. The permeability of the blood brain barrier decreases in developing sterile fetuses into adulthood.


Neurogenesis refers to the development of new functional neurons through the differentiation of neural stem/progenitor cells. A balanced gut microbiota plays a direct or indirect role in maintaining the microenvironment to support the neuronal development process. A number of gut microbial metabolites have recently been identified that have the ability to induce and regulate the prenatal development process, which can pass from the placenta to the fetal compartment. In addition, PG, a bacterial cell wall component, crosses the placenta and reaches the fetal brain, where it activates Toll-like receptor 2 (TLR2), triggering an increase in the expression of FOXG1, a transcription factor important in regulating development and neurogenesis, thereby inducing neuronal proliferation in the forebrain region. Furthermore, gut microbes may indirectly influence neuronal plasticity by regulating neuronal migration and maturation. Gut microbes can influence the fate of neural stem cells by coordinating complex differentiation and survival pathways through neurotrophins and neurotransmitters in different regions of the brain

Serotonin, a neurotransmitter and signaling molecule, can also be synthesized by gut microbes and released into the intestinal lumen, promoting adult neurogenesis. In addition, gut microbes have been shown to play an important role in serotonergic signaling pathways in the gut and in many regions of the brain. Antibiotic use, which has a negative effect on the gut microbiota, has been associated with reduced neurogenesis. Factors such as early life stress and lack of social interaction can also alter the stability of the gut microbiome. Decreased neurogenesis and levels of IL-6 and IL-10 were seen in the hippocampus of socially isolated mice compared to controls living in groups. Decreased hippocampal neurogenesis is strongly associated with impaired learning, anxiety, depressive-like behaviors, neuroinflammation, and again has a clear association with structural changes in the gut microbiome.


Humans are born with unmyelinated axons in the central nervous system (CNS) at birth. Rapid myelination of maturing axons occurs within a few years after birth. There is a variable rate of myelination and myelin content over time until early adulthood. Thus, myelination has the most important role in cognitive function and the scale of myelination has been linked to neuronal plasticity and function. The gut microbiota regulates the critical myelination process by regulating myelination-related gene expression in oligodendrocytes. Myelin deformities can have a detrimental effect on brain function and behavior. Most importantly, the prefrontal cortex region of the brain shows myelination later in life, during the first stage of infancy, making it more vulnerable to external influencing factors such as gut dysbiosis. Irregular myelin formation in this region has a detrimental effect on social behavior. Furthermore, bacterial metabolites have been shown to have a beneficial effect on intestinal barrier dysfunctions and on the regulation of the myelination process. Thus, the microbiota is crucial for myelination and the maintenance of myelin sheath plasticity.

Hypothalamus – Pituitary – Adrenal Axis

The endocrine-neurocrine interaction between the hypothalamus, pituitary gland and adrenal gland in response to stress is known as the hypothalamus-pituitary-adrenal axis. Microbiota has an important role in the development of this axis. Administration of a probiotic formulation consisting of probiotic strains Lactobacillus helveticus and Bifidobacterium longum to mice significantly reduced anxiety levels.

Microglia Development and Physiology

Microglia are resident immune cells that belong to the glial system. They make up 10-15% of the total number of glial cells in the CNS. The functions of microglia include immune defense and maintenance of the CNS. Microglial cells detect pathogens or tissue damage throughout the CNS, which is protected by the blood brain barrier. Abnormal activation of microglia abnormally induces inflammation, which is observed in most brain-related pathologies. Recent research data have shown that microbiota have a vital role in microglia development and maturation.

SOURCE: Dash, S., Syed, Y. A., & Khan, M. R. (2022a). Understanding the role of gut microbiome in brain development and its association with neurodevelopmental psychiatric disorders. Frontiers in Cell and Developmental Biology, 10, 880544.