The central nervous system has essential role in the regulation of the physiological condition of the human body. Gut microbes cause several types of gastrointestinal diseases like ulcer stomach and intestine and irritable bowel syndrome. Microbes present in the human gut can affect brain function by the release of neuroactive metabolites such as neurotransmitters, hormones, and other compounds. Gut microbial-derived metabolites also have an important role in neurological diseases such as Alzheimer's disease, Parkinson's disease, etc. Vital communication between the gut microbes and the central nervous system is known as the microbiota-gut-brain axis. It provides a communication pathway between the gut and brain which is made up of the vagus nerve, immune system components, and neuroendocrine. Disturbance in gut microbiota composition can alter the central nervous system and enteric nervous system functions. Metagenomics has been employed for the identification, and characterization of gut microbes and microbial-derived metabolites. This review is focused on the gut microbes-brain relationship and the role of gut microbes in neurodegenerative diseases. This study is also focused on major metagenomic approaches and their role in gut microbes characterization.