Gut Microbes and Neuropathology: Is There a Causal Nexus?

Abstract

The gut microbiota is a virtual organ which produces a myriad of molecules that the brain and other organs require. Humans and microbes are in a symbiotic relationship, we feed the microbes, and in turn, they provide us with essential molecules. Bacteroidetes and Firmicutes phyla account for around 80% of the total human gut microbiota, and approximately 1000 species of bacteria have been identified in the human gut. In adults, the main factors influencing microbiota structure are diet, exercise, stress, disease and medications. In this narrative review, we explore the involvement of the gut microbiota in Parkinson's disease, Alzheimer's disease, multiple sclerosis and autism, as these are such high-prevalence disorders. We focus on preclinical studies that increase the understanding of disease pathophysiology. We examine the potential for targeting the gut microbiota in the development of novel therapies and the limitations of the currently published clinical studies. We conclude that while the field shows enormous promise, further large-scale studies are required if a causal link between these disorders and gut microbes is to be definitively established.

Keywords: brain-gut-microbiota axis; faecal microbiota transplantation; neurological disorders; prebiotics; probiotics; psychobiotics.

Figure 1

Connections within the brain-gut-microbiota axis, including the vagus nerve, and SCFAs such as butyrate, cytokines and tryptophan. Modified from Ref. [20] 2015 Springer Nature: More than a gut feeling: the microbiota regulates neurodevelopment and behavior. Neuropsychopharmacology 2015; 40: 241–242. Abbreviations: HPA, hypothalamic–pituitary–adrenal; CRH, corticotrophin-releasing hormone; ACTH, adrenocorticotropic hormone; GABA, gamma aminobutyric acid; SCFAs, short-chain fatty acids.

Figure 2

Bidirectional communication between the gut and the brain and how a gut dysbiosis can result in several central pathologies causing neurological dysfunction. Abbreviations: DA, dopamine; BBB, blood–brain barrier.