The microbiota-gut-brain axis: Focus on the fundamental communication pathways

Abstract

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Impact of Microbial Metabolites on Microbiota–Gut–Brain Axis in Inflammatory Bowel Disease

“…The existence of a symbiotic relationship between the gut microbiota and the host is progressively being elucidated by resorting to sophisticated metagenomic, metabolomic, and proteomic approaches as well as to the availability of numerous preclinical animal models including germ-free (GF) and dysbiotic animal models [ 27 ]. The gut microbiota plays a fundamental role in the maintenance of the host health by modulating immune responses, inducing defense mechanisms against pathogens, promoting the fermentation of indigestible dietary fibers, vitamin synthesis, and drug metabolism [ 25 , 26 , 27 ]. Although the microbiota displays some resilience to unstable environmental conditions occurring, for example, as a result of diet modifications or short-term antibiotic treatment [ 32 , 33 ], the combination of several factors such as consumption of high-fat food, drugs, age, and genetics may alter the microflora composition and function, hampering the positive relationship with the host [ 34 , 35 ].…”

“…A complex neural and hormonal reflex network participates in the formation of the gut–brain axis, allowing a bidirectional communication system between the gut and the brain, which are in continuous cross-talking both in health and disease states [ 25 , 26 ] ( Figure 1 ). The anatomic-physiologic conduit of the gut–brain axis is represented by neural pathways of the autonomic nervous system (ANS), the ENS, hormonal (i.e., the hypothalamic-pituitary-adrenal, HPA, axis), and humoral systems [ 25 ].…”

“…A complex neural and hormonal reflex network participates in the formation of the gut–brain axis, allowing a bidirectional communication system between the gut and the brain, which are in continuous cross-talking both in health and disease states [ 25 , 26 ] ( Figure 1 ). The anatomic-physiologic conduit of the gut–brain axis is represented by neural pathways of the autonomic nervous system (ANS), the ENS, hormonal (i.e., the hypothalamic-pituitary-adrenal, HPA, axis), and humoral systems [ 25 ]. Afferent neurons, within the parasympathetic (vagal) have their cell bodies in the nodose vagal ganglion (NVG) and transmit sensory information to the nucleus of the solitary tract (NTS) in the brain stem, and then, to higher centers, such as the paraventricular nucleus of the hypothalamus, or, more locally, inducing long vago-vagal reflexes [ 24 , 89 ].…”

“…This bidirectional communication axis allows signals originating within the central nervous system (CNS) to control gut motor, sensory, secretory, and immune functions. Conversely, messages from the gastrointestinal tract may be conveyed to brain regions, where these signals may influence high functions such as behavior, cognition and emotion regulation, both in normal and disease states [ 25 , 26 , 27 ]. The gut microbiota is a fundamental player in gut–brain communication by releasing a plethora of metabolites, which are involved in the control of local metabolic, neuronal, and immune functions and extend their actions to more distal regions within the CNS, being critical for brain development and homeostasis [ 25 , 26 , 27 ].…”

“…Conversely, messages from the gastrointestinal tract may be conveyed to brain regions, where these signals may influence high functions such as behavior, cognition and emotion regulation, both in normal and disease states [ 25 , 26 , 27 ]. The gut microbiota is a fundamental player in gut–brain communication by releasing a plethora of metabolites, which are involved in the control of local metabolic, neuronal, and immune functions and extend their actions to more distal regions within the CNS, being critical for brain development and homeostasis [ 25 , 26 , 27 ]. In this context, changes within the symbiotic interplay between the host and the saprophytic microflora during IBD may bear important consequences for the host health, underlying not only development of gastrointestinal symptoms but also favoring the patient psychophysiological vulnerability [ 22 , 24 , 28 ].…”