Interplay among gut microbiota, intestinal mucosal barrier and enteric neuro-immune system: a common path to neurodegenerative diseases?

Abstract

Neurological diseases, such as Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis (ALS) and multiple sclerosis, are often associated with functional gastrointestinal disorders. These gastrointestinal disturbances may occur at all stages of the neurodegenerative diseases, to such an extent that they are now considered an integral part of their clinical picture. Several lines of evidence support the contention that, in central neurodegenerative diseases, changes in gut microbiota and enteric neuro-immune system alterations could contribute to gastrointesinal dysfunctions as well as initiation and upward spreading of the neurologic disorder. The present review has been intended to provide a comprehensive overview of the available knowledge on the role played by enteric microbiota, mucosal immune system and enteric nervous system, considered as an integrated network, in the pathophysiology of the main neurological diseases known to be associated with intestinal disturbances. In addition, based on current human and pre-clinical evidence, our intent was to critically discuss whether changes in the dynamic interplay between gut microbiota, intestinal epithelial barrier and enteric neuro-immune system are a consequence of the central neurodegeneration or might represent the starting point of the neurodegenerative process. Special attention has been paid also to discuss whether alterations of the enteric bacterial-neuro-immune network could represent a common path driving the onset of the main neurodegenerative diseases, even though each disease displays its own distinct clinical features.

The progress of gut microbiome research related to brain disorders

“…Neurodegenerative diseases are a collection of neurological diseases that are characterized by progressive loss of neurons, including AD, Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) [168]. Each of the neurodegenerative diseases has been reported to have unique pathologies and clinical features.…”

Irisin reverses intestinal epithelial barrier dysfunction during intestinal injury via binding to the integrin αVβ5 receptor

“…The intact intestinal epithelial monolayer provides an essential structural basis for intestinal absorption and serves as a permeability barrier . Gut ischemia reperfusion (IR) injury, occurring in clinical conditions such as superior mesenteric artery occlusion and intestinal transplantation, severely destroys intestinal barrier functions .…”

Bowel symptoms predate the diagnosis among many patients with multiple sclerosis: A 14‐year cohort study

“…27,28 Such a connection between early ENS dysfunction and subsequent development of MS may reflect the increasingly recognized interplay between gut microbiota, permeability of the GI tract, and the enteric neuro-inflammatory pathway. 23 in this cohort, our findings nevertheless posit a role for bowel complaints as an indication of future, more severe CNS dysfunction more typical of MS.…”

“…Moreover, objective GI alterations were observed throughout the gut in animal models without any CNS spinal cord involvement, suggesting ENS dysfunction as the cause . Such a connection between early ENS dysfunction and subsequent development of MS may reflect the increasingly recognized interplay between gut microbiota, permeability of the GI tract, and the enteric neuro‐inflammatory pathway . While our data do not evaluate the presence or absence of spinal cord lesions prior to CIS diagnosis, it could—in conjunction with the aforementioned animal models—suggest the possible involvement of the ENS prior to demyelination events in MS.…”

“…The interplay between the gut and the central nervous system and its role with other neurodegenerative diseases has been researched previously. Studies have shown the interaction between the gut in diseases, such as Parkinson's disease and Alzheimer's disease, but bowel symptoms have not been fully characterized in MS. Patients with MS frequently report bowel symptoms during the course of their illness after diagnosis, which are associated with decreased quality of life and are thought to be secondary to spinal cord lesions or immobilization .…”