Gut-Brain Axis and Neurodegeneration: State-of-the-Art of Meta-Omics Sciences for Microbiota Characterization

Abstract

Recent advances in the field of meta-omics sciences and related bioinformatics tools have allowed a comprehensive investigation of human-associated microbiota and its contribution to achieving and maintaining the homeostatic balance. Bioactive compounds from the microbial community harboring the human gut are involved in a finely tuned network of interconnections with the host, orchestrating a wide variety of physiological processes. These includes the bi-directional crosstalk between the central nervous system, the enteric nervous system, and the gastrointestinal tract (i.e., gut-brain axis). The increasing accumulation of evidence suggest a pivotal role of the composition and activity of the gut microbiota in neurodegeneration. In the present review we aim to provide an overview of the state-of-the-art of meta-omics sciences including metagenomics for the study of microbial genomes and taxa strains, metatranscriptomics for gene expression, metaproteomics and metabolomics to identify and/or quantify microbial proteins and metabolites, respectively. The potential and limitations of each discipline were highlighted, as well as the advantages of an integrated approach (multi-omics) to predict microbial functions and molecular mechanisms related to human diseases. Particular emphasis is given to the latest results obtained with these approaches in an attempt to elucidate the link between the gut microbiota and the most common neurodegenerative diseases, such as multiple sclerosis (MS), Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS).

Keywords: gut microbiota; gut–brain axis; meta-omics sciences; neurodegenerative diseases.

Figure 1

Major mechanisms employed by gut microbiota to impact neurodegenerative diseases. The figure depicts the most relevant endogenous (i.e., age, gender) and environmental (i.e., diet, environment, and drugs) variables affecting gut microbiota composition and functions. In turn, microbiota dysbiosis impacts neurodegenerative diseases through direct production of neuroactive molecules (e.g., short-chain fatty acid (SCFAs), neurotransmitters) and/or stimulation of neuroactive mediator production by the secretory epithelial cell (e.g., Citokynes, chemokine, gut peptides). Examples of neuroactive molecules are mentioned in the figure. Ach: Acetylcholine; His: Histidine; DA: Dopamine; 5-HT: Serotonin; NpY: Neuropeptide-Y; CcK: Cholecystokinin; ILs: Interleukins; TNF: Tumor Necrosis Factor; CRP: C-Reactive Protein.