Microbiota-Gut-Brain Axis: Mass-Spectrometry-Based Metabolomics in the Study of Microbiome Mediators-Stress Relationship.

The microbiota-gut-brain axis is a complex bidirectional communication system that involves multiple interactions between intestinal functions and the emotional and cognitive centers of the brain. These interactions are mediated by molecules (metabolites) produced in both areas, which are considered mediators. To shed light on this complex mechanism, which is still largely unknown, a reliable characterization of the mediators is essential. Here, we review the most studied metabolites in the microbiota-gut-brain axis, the metabolic pathways in which they are involved, and their functions. This review focuses mainly on the use of mass spectrometry for their determination, reporting on the latest analytical methods, their limitations, and future perspectives. The analytical strategy for the qualitative-quantitative characterization of mediators must be reliable in order to elucidate the molecular mechanisms underlying the influence of the above-mentioned axis on stress resilience or vulnerability.