Trends in Molecular Medicine
Volume 20, Issue 9, September 2014, Pages 509-518
Journal home page for Trends in Molecular Medicine

Review
Microbiota and neurodevelopmental windows: implications for brain disorders

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Highlights

Gut microbiota is essential to human health, playing a major role in the bidirectional communication between the gastrointestinal tract and the central nervous system. The microbiota undergoes a vigorous process of development throughout the lifespan and establishes its symbiotic rapport with the host early in life. Early life perturbations of the developing gut microbiota can impact neurodevelopment and potentially lead to adverse mental health outcomes later in life. This review compares the parallel early development of the intestinal microbiota and the nervous system. The concept of parallel and interacting microbial–neural critical windows opens new avenues for developing novel microbiota-modulating based therapeutic interventions in early life to combat neurodevelopmental deficits and brain disorders.

Section snippets

Microbiota–gut–brain axis

Microbes within and on our bodies are a thriving dynamic population forming a symbiotic superorganism. The collective comprises a myriad of bacteria, of approximately 1014 cells, containing 100 times the number of genes of the human genome [1]. Despite the evolution of this microbiome (see Glossary) for 500 million years 2, 3, it is only recently that advances in sequencing technology have allowed us to appreciate the full nature of the complexities of host–microbe relationships. The largest

Developmental windows: gut microbiota and neurodevelopment

The prenatal and postnatal periods in mammalian development are critical developmental windows that are characterized by rapid changes in neuronal and microbial organization. During these periods environmental factors could have a long-term impact on brain and behavior, resulting in brain disorders (Figure 2). Brain development requires a delicate and complex balance of genetic and environmental factors both during prenatal and postnatal periods. Disruption of these elements can alter

Microbiota development

Despite a common dogma that the intrauterine environment and fetus are sterile until delivery, some evidence demostrates bacterial presence in the intrauterine environment, suggesting that these bacteria may influence the microbiota of the infant before birth 26, 27, 28, 29, 30. The presence of bacterial species in the fetus (such as Escherichia coli, Enterococcus faecium, and Staphylococcus epidermidis) could result from the translocation of the mother's gut bacteria via the bloodstream and

Microbiota development

During and shortly after birth, infants are exposed to microbes mainly originating from the mother. Growing evidence suggests that it is the inoculation and subsequent development of the intestinal microbiota in early life that is crucial for healthy development, especially neurodevelopment. The most dramatic changes in the composition of the intestinal microbiota take place postnatally. A plethora of factors influence the composition of the infant gut microbiota and potential functional

Microbiota development

The gut microbiota, following initial colonization during infancy and birth, continues to develop throughout childhood and adolescence. Gradual changes in microbiota composition occur during early childhood, with a general reduction in the number of aerobes and facultative anaerobes and an increase in the populations of anaerobic species [64]. Although it is generally assumed that children's gut microbiota resembles that of an adult [65], recent studies demonstrate a less diverse microbiota

Adulthood and aging

As adulthood approaches, the gut microbiota stabilizes and becomes more diverse [65]. The adult gut microbiota is individual-specific and remains relatively stable over time [65], and can resist detrimental environmental elements such as use of antibiotics and stress by restoring its diverse and stable ‘normal’ core microbiota [73]. However, it is worth noting that recent evidence challenges the idea of the gut microbiota as stable during adulthood [74], suggesting that gut microbes can be

Brain disorders and the microbiota–gut–brain axis: autism and beyond

Maternal infection and stress during pregnancy have been shown to increase the risk for neurodevelopmental disorders such as schizophrenia and autism in offspring (or distinct cognitive and behavioral pathological symptoms in later life). This association appears to be critically dependent on the precise prenatal timing of the insult. Neurodevelopmental disorders are characterized by impaired brain development and behavioral, cognitive, and/or physical abnormalities. Several share behavioral

Concluding remarks and future perspectives

It is becoming clear that perturbations in microbiota can contribute to neurodevelopmental and psychiatric disorders onset later in life. Knowing that the microbiota can significantly interfere with the human cognitive and immune systems, the initiation of symbiosis, especially during prenatal, early postnatal, and adolescence phases appears to be a crucial step for optimizing brain development overall and mental health later in life. Although there seem to be critical windows in neurological

Glossary

Alzheimer's disease
a progressive age-associated neurodegenerative disorder characterized by cognitive decline and build-up of protein ‘plaques’ and ‘tangles’ in the brain.
Astrocytes
the most abundant glial cell of the human brain, providing support for the blood–brain barrier, provision of nutrients to the nervous tissue, and a role in the repair and scarring process of the CNS following traumatic injuries.
Attention deficity hyperactivity disorder (ADHD)
a psychiatric disorder usually occurring

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