Current Perspectives and Mechanisms of Relationship between Intestinal Microbiota Dysfunction and Dementia: A Review

BACKGROUND: Accumulating data suggest a crucial role of the intestinal microbiota in the development and progression of neurodegenerative diseases. More recently, emerging reports have revealed an association between intestinal microbiota dysfunctions and dementia, a debilitating multifactorial disorder, characterized by progressive deterioration of cognition and behavior that interferes with the social and professional life of the sufferer. However, the mechanisms of this association are not fully understood. SUMMARY: In this review, I discuss recent data that suggest mechanisms of cross-talk between intestinal microbiota dysfunction and the brain that underlie the development of dementia. Potential therapeutic options for dementia are also discussed. The pleiotropic signaling of the metabolic products of the intestinal microbiota together with their specific roles in the maintenance of both the intestinal and blood-brain barriers as well as regulation of local, distant, and circulating immunocytes, and enteric, visceral, and central neural functions are integral to a healthy gut and brain. KEY MESSAGES: Research investigating the effect of intestinal microbiota dysfunctions on brain health should focus on multiple interrelated systems involving local and central neuroendocrine, immunocyte, and neural signaling of microbial products and transmitters and neurohumoral cells that not only maintain intestinal, but also blood brain-barrier integrity. The change in intestinal microbiome/dysbiome repertoire is crucial to the development of dementia.