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

Acta Neuropathol. 2018 Sep;136(3):345-361. doi: 10.1007/s00401-018-1856-5. Epub 2018 May 24.


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.

Keywords: Animal models; Enteric neuro-immune system; Gut microbiota; Gut–brain axis; Intestinal mucosal barrier; Neurodegenerative diseases; Patients.

Publication types

  • Review

MeSH terms

  • Animals
  • Enteric Nervous System / microbiology*
  • Enteric Nervous System / pathology
  • Gastrointestinal Microbiome / physiology*
  • Humans
  • Intestinal Mucosa / microbiology*
  • Intestinal Mucosa / pathology
  • Neurodegenerative Diseases / microbiology*
  • Neurodegenerative Diseases / pathology