The Intestinal Ecosystem in Neuroinflammation and Neuroprotection: Mechanistic Insights and Emerging Evidence With Recent Advancements

The intestinal ecosystem (gut microbiota, intestinal mucosa, intestinal immune cells, neuronal components (enteric nervous system and vagus nerve), and metabolic products of microbes) has a potent influence on homeostasis of the central nervous system (CNS). The mounting preclinical and clinical evidence is pointing towards the involvement of gut-derived signals in both neuroinflammatorysignaling and neuroprotectivesignaling to exacerbate neurological disease and maintain neuronal activity respectively. It is a survey of mechanistic knowledge (barrier integrity, immune modulation, microbial metabolites, vagal and enteric signaling), clinical and experimental evidence on large-scale disorders (Alzheimer's disease, Parkinson's disease, multiple sclerosis, stroke, autism spectrum disorder), and new ways of therapeutic intervention (dietary modulation, psychobiotics, fecal microbiota transplantation, metabolites and receptor-targeted drugs, and neuromodulation). We present unanswered questions and give a roadmap of a translational research and clinical trials to implement the intestinal environment to shield the brain.