Trends in Molecular Medicine
ReviewMicrobiota and neurodevelopmental windows: implications for 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
References (114)
- et al.
Brain–gut axis in health and disease
Gastroenterology
(1998) - et al.
Brain–gut interactions in inflammatory bowel disease
Gastroenterology
(2013) Probiotics treatment improves diabetes-induced impairment of synaptic activity and cognitive function: behavioral and electrophysiological proofs for microbiome–gut–brain axis
Neuroscience
(2013)Altered gut microbiota and activity in a murine model of autism spectrum disorders
Brain Behav. Immun.
(2014)Is meconium from healthy newborns actually sterile?
Res. Microbiol.
(2008)Early life programming and neurodevelopmental disorders
Biol. Psychiatry
(2010)State of the art; microbiology in health and disease, Intestinal bacterial flora in autism
Anaerobe
(2011)Campylobacter jejuni infection increases anxiety-like behavior in the holeboard: possible anatomical substrates for viscerosensory modulation of exploratory behavior
Brain Behav. Immun.
(2008)Mode of delivery affects the bacterial community in the newborn gut
Early Hum. Dev.
(2010)Can nutritional modulation of maternal intestinal microbiota influence the development of the infant gastrointestinal tract?
J. Nutr.
(2012)
Synaptophysin and postsynaptic density protein 95 in the human prefrontal cortex from mid-gestation into early adulthood
Neuroscience
Variation in human intestinal microbiota with age
Dig. Liver Dis.
A higher mutational burden in females supports a “female protective model” in neurodevelopmental disorders
Am. J. Hum. Genet.
Sex differences in anxiety and depression: role of testosterone
Front. Neuroendocrinol.
Epidemiology of inflammatory bowel disease
Gastroenterol. Clin. North Am.
Gut microbiota: changes throughout the lifespan from infancy to elderly
Int. Dairy J.
Ageing and gut microbes: perspectives for health maintenance and longevity
Pharmacol. Res.
Executive function deficits in autism spectrum disorders and attention-deficit/hyperactivity disorder: examining profiles across domains and ages
Brain Cogn.
Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders
Cell
Cytokine, sickness behavior, and depression
Immunol. Allergy Clin. North Am.
Activation in vagal afferents and central autonomic pathways: early responses to intestinal infection with Campylobacter jejuni
Brain Behav. Immun.
Mood and gut feelings
Brain Behav. Immun.
Induction of anxiety-like behavior in mice during the initial stages of infection with the agent of murine colonic hyperplasia Citrobacter rodentium
Physiol. Behav.
The probiotic Bifidobacteria infantis: an assessment of potential antidepressant properties in the rat
J. Psychiatr. Res.
Diversity of the human intestinal microbial flora
Science
The human microbiome: at the interface of health and disease
Nat. Rev. Genet.
Microbial genes, brain & behaviour – epigenetic regulation of the gut–brain axis
Genes Brain Behav.
Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour
Nat. Rev. Neurosci.
Gut microbiota and gastrointestinal health: current concepts and future directions
Neurogastroenterol. Motil.
Principles and clinical implications of the brain–gut–enteric microbiota axis
Nat. Rev. Gastroenterol. Hepatol.
The interplay between the intestinal microbiota and the brain
Nat. Rev. Microbiol.
Maternal separation as a model of brain–gut axis dysfunction
Psychopharmacology (Berl.)
Gut feelings: the emerging biology of gut–brain communication
Nat. Rev. Neurosci.
Brain–gut–microbe communication in health and disease
Front. Physiol.
The microbiome–gut–brain axis: from bowel to behavior
Neurogastroenterol. Motil.
Gut feelings: bacteria and the brain
Cerebrum
The microbiome: stress, health and disease
Mamm. Genome
Normal gut microbiota modulates brain development and behavior
Proc. Natl. Acad. Sci. U.S.A.
Neuropaediatric and neuroarchaeology: understanding development to correct brain disorders
Acta Paediatr.
Neurodevelopmental model of schizophrenia: update 2012
Mol. Psychiatry.
Prenatal exposure to drugs: effects on brain development and implications for policy and education
Nat. Rev. Neurosci.
Postnatal microbial colonization programs the hypothalamic–pituitary–adrenal system for stress response in mice
J. Physiol.
Systems-matching by degeneration II. Interpretation of the generation and degeneration of retinal ganglion cells in the chicken by a mathematical model
Exp. Brain Res.
Numerical matching during cerebellar development: quantitative analysis of granule cell death in staggerer mouse chimeras
J. Neurosci.
Modeling transformations of neurodevelopmental sequences across mammalian species
J. Neurosci.
Mom knows best: the universality of maternal microbial transmission
PLoS Biol.
Microbial prevalence, diversity and abundance in amniotic fluid during preterm labor: a molecular and culture-based investigation
PLoS ONE
Bifidobacterium and Lactobacillus DNA in the human placenta
Lett. Appl. Microbiol.
Probiotics modulate host–microbe interaction in the placenta and fetal gut: a randomized, double-blind, placebo-controlled trial
Neonatology
Isolation of commensal bacteria from umblicial cord blood of healthy neonates born by cesarean section
Curr. Microbiol.
Cited by (788)
Can bumetanide be a miraculous medicine for autism spectrum disorder: Meta-analysis evidence from randomized controlled trials
2024, Research in Autism Spectrum DisordersAltering the Gut Microbiome for Cognitive Benefit
2024, The Gut-Brain Axis, Second Edition