For some time, the concept of the gut-brain axis has served as a useful paradigm to explain the many interactions between the “big brain” (the central nervous system [CNS]) and the “little brain” (the enteric nervous system). Recently, the gut microbiome has been added to the equation and the proposition that gut microbes could influence brain structure and function and vice versa has emerged. Research in this field has been facilitated by dramatic progress in technologies that permit the delineation of the microbial constituents of the gut and their function in health and disease. Studies in a variety of animal models have amply supported the concept of a microbiota-gut-brain-axis and demonstrated that interventions that modulate the microbiome can influence animal behavior and CNS physiology. Understandably, studies of the impact of the microbiome on human brain structure and function are less numerous, but sufficient evidence does exist to indicate that this axis is operating in humans. In terms of neurodegenerative disorders, here again animal data dominate, but a sufficient body of evidence has accumulated to justify further explorations of the role of gut microbiota in Parkinson’s disease and Alzheimer’s disease, as well as in the aging process per se—“inflammaging.” Many confounding factors complicate the interpretation of human studies of the microbiome, and large, longitudinal studies that attempt to account for such confounders are needed. A number of interventions can be entertained—most notably, diet, probiotics, and prebiotics. To date, studies of any such interventions in neurodegenerative disease in humans are scanty.
Deubiquitylating enzymes in neuronal health and disease