There is increasing evidence showing that the dynamic changes in the gut microbiota can alter brain physiology and behavior. Cognition was originally thought to be regulated only by the central nervous system. However, it is now becoming clear that many non-nervous system factors, including the gut-resident bacteria of the gastrointestinal tract, regulate and influence cognitive dysfunction as well as the process of neurodegeneration and cerebrovascular diseases. Extrinsic and intrinsic factors including dietary habits can regulate the composition of the microbiota. Microbes release metabolites and microbiota-derived molecules to further trigger host-derived cytokines and inflammation in the central nervous system, which contribute greatly to the pathogenesis of host brain disorders such as pain, depression, anxiety, autism, Alzheimer’s diseases, Parkinson’s disease, and stroke. Change of blood–brain barrier permeability, brain vascular physiology, and brain structure are among the most critical causes of the development of downstream neurological dysfunction. In this review, we will discuss the following parts: Overview of technical approaches used in gut microbiome studies Microbiota and immunity Gut microbiota and metabolites Microbiota-induced blood–brain barrier dysfunction Neuropsychiatric diseases ■ Stress and depression ■ Pain and migraine ■ Autism spectrum disorders Neurodegenerative diseases ■ Parkinson’s disease ■ Alzheimer’s disease ■ Amyotrophic lateral sclerosis ■ Multiple sclerosis Cerebrovascular disease ■ Atherosclerosis ■ Stroke ■ Arteriovenous malformation Conclusions and perspectives