Abstract
The gut microbiota is a complex and dynamic ecosystem essential for the proper functioning of the organism, affecting the health and disease status of the individuals. There is continuous and bidirectional communication between gut microbiota and the host, conforming to a unique entity known as “holobiont”. Among these crosstalk mechanisms, the gut microbiota synthesizes a broad spectrum of bioactive compounds or metabolites which exert pleiotropic effects on the human organism. Many of these microbial metabolites can cross the blood–brain barrier (BBB) or have significant effects on the brain, playing a key role in the so-called microbiota-gut-brain axis. An altered microbiota-gut-brain (MGB) axis is a major characteristic of many neuropsychiatric disorders, including major depressive disorder (MDD). Significative differences between gut eubiosis and dysbiosis in mental disorders like MDD with their different metabolite composition and concentrations are being discussed. In the present review, the main microbial metabolites (short-chain fatty acids -SCFAs-, bile acids, amino acids, tryptophan -trp- derivatives, and more), their signaling pathways and functions will be summarized to explain part of MDD pathophysiology. Conclusions from promising translational approaches related to microbial metabolome will be addressed in more depth to discuss their possible clinical value in the management of MDD patients.
Highlights
Microorganisms belonging to the human body are acquiring more relevance nowadays as they establish mutualistic relationships with our cells modulating our health status
Another type of SCFA, isovaleric acid has been shown to be correlated with certain bacterial populations related to major depressive disorder (MDD) and augmented cortisol levels
There are some bacteria capable of using betaine obtained from dietary sources like Akkermansia muciniphila leading to some favorable effects due to the increase of SCFAs production and restoring gut microbial populations [172,173]
Summary
Microorganisms belonging to the human body are acquiring more relevance nowadays as they establish mutualistic relationships with our cells modulating our health status. ) playing a key role in the homeostasis by communicating bidirectionally with host immune cells and functions In this context, the Human Microbiome Project (HMP) was born in 2007 collecting biological and clinical data for the research of microbiome populations and behavior in health and disease [3]. The dysbiosis condition is known to have a significant correlation with immunological and neuroimmunological status in physical and psychological pathologies This imbalance leads to a disruption in the already known microbiota-gut-brain axis (MGB) and explains part of the altered microbial and human production of neurotransmitters like serotonin, dopamine, gamma-aminobutyric acid (GABA), and noradrenaline [11], and the distorted crosstalk dialogue of other microbial metabolites with neuroimmune functions. After brief statements about the biological basis of MDD and microbial metabolites motion in the pathophysiology of this condition; this descriptive review mainly aims to gather the most recent updates related to translational applications of bioactive compounds equivalent to microbial products and other feasible ways to target gut microbiota functioning, from research to clinical practice, all in the MDD framework
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