Understanding the Role of the Gut Microbiome in Brain Development and Its Association With Neurodevelopmental Psychiatric Disorders

Abstract

The gut microbiome has a tremendous influence on human physiology, including the nervous system. During fetal development, the initial colonization of the microbiome coincides with the development of the nervous system in a timely, coordinated manner. Emerging studies suggest an active involvement of the microbiome and its metabolic by-products in regulating early brain development. However, any disruption during this early developmental process can negatively impact brain functionality, leading to a range of neurodevelopment and neuropsychiatric disorders (NPD). In this review, we summarize recent evidence as to how the gut microbiome can influence the process of early human brain development and its association with major neurodevelopmental psychiatric disorders such as autism spectrum disorders, attention-deficit hyperactivity disorder, and schizophrenia. Further, we discuss how gut microbiome alterations can also play a role in inducing drug resistance in the affected individuals. We propose a model that establishes a direct link of microbiome dysbiosis with the exacerbated inflammatory state, leading to functional brain deficits associated with NPD. Based on the existing research, we discuss a framework whereby early diet intervention can boost mental wellness in the affected subjects and call for further research for a better understanding of mechanisms that govern the gut-brain axis may lead to novel approaches to the study of the pathophysiology and treatment of neuropsychiatric disorders.

Maternal microbes and early brain development in mouse

“…Gut microbe metabolites were shown to regulate the expression of genes and processes involved in neural stem cell differentiation, neurogenesis, and development (20,21,70). Also, gut-derived neuroactive substances such as tryptophan and serotonin modulate the inflammatory status and function of the microglia in the central nervous system (CNS) (71,72).…”

Repurposing SGLT2 Inhibitors for Neurological Disorders: A Focus on the Autism Spectrum Disorder

“…This explains why infants fed on cow’s milk formula had a drastically increased plasma osmolality which affected the homeostasis hemodynamics of the brain development negatively, compared to the breast-fed infants, emphasizing the gut microbiota-brain axis association to neurodevelopmental disorders [ 30 , 31 ]. The microbiome is essential for the microglial maturation process and taking control of the CNS glial activation, thus regulating the inflammation in the CNS, as the gut dysbiosis impacts the immune system homeostasis, which leads to developmental delays and to the developmental pathway disruption [ 32 ].…”

Understanding and harnessing triple-negative breast cancer-related microbiota in oncology

“…This site-specific diversity and dynamics can be regarded as a health indicator with, high diversity in the gut microbiome generally linked to good health ( 18 ). Our microbiomes represent a virtual organ that performs essential body functions that maintain our homeostasis, such as metabolizing nutrients, maintaining the integrity of the mucosal barriers, developing a healthy immune system, modulating a healthy neuronal development (including regulating our moods) and defending us against pathogens ( 19 – 21 ).…”