Reverse engineering the Gut-Brain Axis and microbiome-metabolomics for symbiotic/pathogenic balance in neurodegenerative diseases

Deciphering the molecular communications along the gut-brain axis can help in understanding the pathophysiology of neurodegenerative diseases and exploiting the gut microbiome for therapeutics. However, gut microbes and their metabolites have a multifaceted role in mediating both brain physiology and neurodegenerative pathology. There is a lack of understanding of how and when this role is tipped in neurodegenerative diseases and what are those contributing factors, both at local (gut) and distal (neuronal) levels, that drive this imbalance. Here we have reviewed the gut microbiome and its metabolites in the context of the gut-brain axis and summarized how different factors such as gut-microbial diversity, their metabolites, the role of the native immune system and the integrity of gut epithelial and blood-brain barriers are interconnected and collectively define the involvement of gut-microbiome in neurodegenerative pathologies. It also underlines the need for multidisciplinary tools and animal models to simultaneously reflect on many of these factors and to better correlate with clinical observations and data obtained from human biopsies and fecal samples. Harnessing the gut-brain axis will herald a paradigm shift in medicine for neurodegenerative diseases and aging, emphasizing the significance of the microbiome in the broader spectrum of health and disease.