Does the Gut Microbial Metabolome Really Matter? The Connection between GUT Metabolome and Neurological Disorders

Abstract

Herein we gathered updated knowledge regarding the alterations of gut microbiota (dysbiosis) and its correlation with human neurodegenerative and brain-related diseases, e.g., Alzheimer's and Parkinson's. This review underlines the importance of gut-derived metabolites and gut metabolic status as the main players in gut-brain crosstalk and their implications on the severity of neural conditions. Scientific evidence indicates that the administration of probiotic bacteria exerts beneficial and protective effects as reduced systemic inflammation, neuroinflammation, and inhibited neurodegeneration. The experimental results performed on animals, but also human clinical trials, show the importance of designing a novel microbiota-based probiotic dietary supplementation with the aim to prevent or ease the symptoms of Alzheimer's and Parkinson's diseases or other forms of dementia or neurodegeneration.

Keywords: Alzheimer’s disease; Parkinson’s disease; gut microbiota; metabolome; microbiome; neurodegeneration; probiotics.

Figure 1

The interplay between the microbiome, microbial metabolites, and neuropathological processes present during neurodegenerative diseases such as AD and PD. The microbiome and microbial metabolites could regulate brain homeostasis via four different ways: 1. direct absorption of specific metabolites which have the ability to cross the BBB; 2. interaction between peripheral immune systems, which interact with brain glia cells and astrocytes; 3. influence on gut hormones and the enteroendocrine system; 4. communication via the vagus nerve. These four routes may have an influence on pathological symptoms such as increased BBB leakage and neural inflammation, enhanced beta-amyloid and alpha-synuclein formation, and finally neuron loss and motor/cognitive deficits.

Figure 2

A healthy, abundant, and diverse microbiome (left side) is able to produce proper amounts of SCFAs, amino acids, and neurotransmitters. This type of microbiome and its metabolites positively influence gut barrier integrity and leads to the healthy maturation of the peripheral immune system, which is able to counteract external immune stimuli properly. A dysbiotic microbiome (right side) could be characterized by reduced diversity and an abundance of species able to produce positive metabolites and an increased abundance of species producing harmful metabolites such as LPS, beta-amyloids, small toxic metabolites, or other toxins. These switches may lead to disruption in the intestinal barrier, increased absorption of toxic metabolites, over-activation of the immune system, and, finally, pro-inflammatory responses which influence other organs, including the brain.