Impact of gut microbiota on neurogenesis and neurological diseases during infancy
Introduction
During childhood, the brain is exposed to environmental factors that can shape synaptic connections and neuronal circuits, with subsequent influence on behavior and learning processes [1,2]. Over the crucial periods of neurodevelopment, the neuronal circuits are extremely plastic and can be easily subjected to remodel in response to experience, which constitute windows of opportunity [3]. Furthermore, gut microbiota colonization occurs simultaneously with this dynamic phase of postnatal brain development, including cell differentiation, axon myelination and synaptogenesis, and the rapid emergence of infant cognitive functions [4]. Subsequently, the diversity of commensal species within less-heterogeneous communities increases with age as well as the metabolic landscape of gut microbial metabolic pathways and the repertoire of microbiota-derived molecules [5] that have been shown to modulate brain development and influence the fine maturation of the brain with long lasting effects [4]. Accordingly, recent studies support a functional communication between the central nervous system (CNS) and the gastrointestinal (GI) tract, known as gut–brain axis, in which the intestinal microbiome is proposed to play a key role in these neurophysiological processes. The complex relationship between gut microbiota and the host has given rise to the notion of the microbiota-gut–brain axis [6,7]. In spite of the specific mechanisms underlying this influence, these mechanisms remain still unknown. On one side, the neuroendocrine, neuroimmune and autonomic nervous systems, and in the other side, the microbiotic toxin production, have been proposed as potential communication routes between gut microbiota and the brain [8].
In this review, we discuss the knowledge about the contribution of gut microbiota during the development of the nervous system and the main mechanisms of communication between microbiota-gut–brain axis. Finally, we address the role of microbiota in the pathogenesis of CNS disorders.
Section snippets
Neurogenesis: the link with gut microbiota
Broad evidence suggests that the birth of new neurons, known as neurogenesis, has an important role in learning and memory and responses to stress and antidepressant drugs [9]. The literature indicates that the permeability of maternal-fetal interface allows bacterial peptidoglycan to traverse the placenta to activate Toll-like receptor 2 (TLR2), causing alterations in fetal neural development and having a potential impact on cognitive function later in life [10,11]. In fact, it has been
From gut microbiota to brain: communication mechanisms
In the past decade, several studies have shown mechanisms that relate CNS and gut microbiota community, which involve microbiota metabolites, the vagus nerve, the hypothalamic-pituitary-adrenal (HPA) axis modulation and the immune system. Communication from the gut microbiota to the CNS primarily occurs through microbial-derived intermediates, such as short-chain fatty acids (SCFAs) [25], tryptophan metabolites [26] and secondary bile acids (2BAs) [27]. Some of these intermediates interact
Gut microbiota and CNS disorders
Since gut microbiota influences CNS through various pathways, it is necessary to take into account its contribution in the development of neurological disorders.
In patients with autism spectrum disorder (ASD), have been identified mutations and deletion of proteins of the SH3 and multiple ankyrin repeat domains (SHANK) gene-family, which have a role in the CNS synaptogenesis [43]. Recently, Sauer et al. observed in Shank3 knock-out (KO) mice the expression of that protein in the
Future perspectives and conclusions
It is necessary to develop new effective strategies for the treatment of CNS diseases, as consequence of their complicated etiologies and absence of biomarkers in humans.
Recent findings have shown that microbial metabolites, directly or indirectly, may give rise to changes in immunological activities in the brain, leading to neurological alterations and making a link between microbiota, immune signaling and the CNS.
New therapeutic modulators have been found in several mood disorders, delivering
Funding
Supported by funds from European Union 7th FP KBBE.2013.2.2-02—MyNewGut Project (‘Factors influencing the human gut microbiome and its effect on the development of diet-related diseases and brain development’, Grant Agreement 613979) and from the Spanish Ministry of Economy and Competitiveness GD-Brain Project (SAF2015-69265-c2.2).
Conflict of interest statement
Nothing declared.
References and recommended reading
Papers of particular interest, published within the period of review, have been highlighted as:
• of special interest
•• of outstanding interest
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