Mass spectrometry‐based metabolomics: Targeting the crosstalk between gut microbiota and brain in neurodegenerative disorders

Abstract

Metabolomics seeks to take a "snapshot" in a time of the levels, activities, regulation and interactions of all small molecule metabolites in response to a biological system with genetic or environmental changes. The emerging development in mass spectrometry technologies has shown promise in the discovery and quantitation of neuroactive small molecule metabolites associated with gut microbiota and brain. Significant progress has been made recently in the characterization of intermediate role of small molecule metabolites linked to neural development and neurodegenerative disorder, showing its potential in understanding the crosstalk between gut microbiota and the host brain. More evidence reveals that small molecule metabolites may play a critical role in mediating microbial effects on neurotransmission and disease development. Mass spectrometry-based metabolomics is uniquely suitable for obtaining the metabolic signals in bidirectional communication between gut microbiota and brain. In this review, we summarized major mass spectrometry technologies including liquid chromatography-mass spectrometry, gas chromatography-mass spectrometry, and imaging mass spectrometry for metabolomics studies of neurodegenerative disorders. We also reviewed the recent advances in the identification of new metabolites by mass spectrometry and metabolic pathways involved in the connection of intestinal microbiota and brain. These metabolic pathways allowed the microbiota to impact the regular function of the brain, which can in turn affect the composition of microbiota via the neurotransmitter substances. The dysfunctional interaction of this crosstalk connects neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease and Huntington's disease. The mass spectrometry-based metabolomics analysis provides information for targeting dysfunctional pathways of small molecule metabolites in the development of the neurodegenerative diseases, which may be valuable for the investigation of underlying mechanism of therapeutic strategies.

Antidepressive Mechanisms of Probiotics and Their Therapeutic Potential

“…Without gut microbiota, the excitability of enteric neurons would likely be attenuated, based on data observed in GF mice . Through the ENS, gut microbiota and the brain communicate bidirectionally through neural and humoral (systemic circulation) pathways (Luan et al, 2017). Parasympathetic vagus afferents carry neural information from internal organs, including the gut, to the brain (Breit et al, 2018).…”

“…The decrease in Faecalibacterium, Bifidobacterium, Lactobacillus (Aizawa et al, 2016), and Dialister (Kelly et al, 2016), and increase in Clostridium, Streptococcus, Klebsiella, Oscillibacter, Allistipes (Naseribafrouei et al, 2014;Jiang et al, 2015;Lin et al, 2017;Rong et al, 2019), Eggerthella, Holdemania, Gelria, Turicibacter, Paraprevotella, and Anaerofilum (Kelly et al, 2016) genera have been found among MDD patients. This shift in the gut microbiota composition may contribute to a shift in the regulation of the host physiology (Luan et al, 2017). It is, thus, worthwhile to tackle MDD from the MGB axis standpoint, with an emphasis on the gut microbiota.…”

Altered Bile Acid Profile in Mild Cognitive Impairment and Alzheimer’s Disease: Relationship to Neuroimaging and CSF Biomarkers

“…[6,7] Recent work suggests microbial disturbances linked to BA profiles are implicated in neurodegenerative disorders. [8][9][10][11][12][13] The gut microbiota are involved in immune, neuroendocrine, and neural pathways [10,11,[14][15][16][17][18], have been shown to regulate microglial maturation and function, and may contribute to AD. [18,19] Peripheral metabolic changes may influence central changes through the liver and gut-brain axis that includes commensal and pathogenic bacteria, through its interactions with the vagus nerve, changes in central nervous system functioning, the immune system [20,21], and hippocampal neurogenesis.…”

Intestinal Organoids: A Tool for Modelling Diet–Microbiome–Host Interactions

“…However, bulk omics approaches, such as proteomics and metabolomics, eliminate all spatial information, morphology, and heterogeneity, which are vital to disentangle the essence of such complex eukaryotic-prokaryotic networks. To overcome these limitations, mass spectrometry imaging (MSI) has emerged as a novel potent tool to assess the heterogeneity of a tissue at a single cell resolution [92][93][94][95]. Thus, by determining the spatial distribution and abundance of known or unknown molecular species, MSI can identify the cellular distribution of specific GMMs in the IO epithelium, the biotransformation of such compounds in metabolites, and the metabolic and/or proteomic response of intestinal cells to the compound [96].…”