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.
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Lack of a "healthy" microbiota is associated with many forms of disease, including metabolic diseases, gastrointestinal cancer, inflammatory bowel disease, renal disease, and neurodegenerative diseases associated with aging.
“Lack of a “healthy” microbiota is associated with many forms of disease (19–24), such as metabolic diseases (obesity, type 2 diabetes), gastrointestinal cancer, inflammatory bowel disease, and renal disease, as well as neurodegenerative diseases (NDs) associated with aging, in which the activity and composition of the gut microbiota change during the life cycle.”
From Modulation of the gut–brain axis via the gut microbiota: a new era in treatment of amyotrophic lateral sclerosis (2023) · cites this paper as [24]
The intestinal microbiota and its metabolites can produce serotonin, norepinephrine, and GABA through stimulation of intestinal chromogranin cells, and these neurotransmitters can reach the brain and directly affect central nervous system function through the intestinal epithelium or the blood-brain barrier.
“The intestinal microbiota and its metabolites (e.g., SCFAs) can also produce serotonin, norepinephrine, and GABA through stimulation of intestinal chromogranin cells (52), and these neurotransmitters can reach the brain and directly affect central nervous system function through the intestinal epithelium or the BBB (24).”
From Modulation of the gut–brain axis via the gut microbiota: a new era in treatment of amyotrophic lateral sclerosis (2023) · cites this paper as [24]
Pathological changes in the composition of the intestinal microbiota can lead to disruption of the intestinal epithelial barrier and increased mucosal permeability.
“Studies have shown (24) that pathological changes in the composition of the intestinal microbiota can lead to disruption of the intestinal epithelial barrier and increased mucosal permeability.”
From Modulation of the gut–brain axis via the gut microbiota: a new era in treatment of amyotrophic lateral sclerosis (2023) · cites this paper as [24]
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“…human cohorts have consistently demonstrated alterations of the Firmicutes-to-Bacteroidetes ratio, with a relative decrease in butyrate-producing species ( Faecalibacterium prausnitzii , Roseburia spp., Eubacterium rectale ) and an increase in pro-inflammatory Gram-negative species [22,54,56,61].”
- Authors
- Pellegrini, C., Antonioli, L., Colucci, R., Blandizzi, C., & Fornai, M.
- Affiliations
- University of Pisa (IT)
- University of Padua (IT)
- Corresponding author
- Pellegrini, Carolina
- Venue
- Acta Neuropathologica
- Published
- 2018-05-24
- Volume
- 136
- Issue
- 3
- Pages
- 345-361
- ISSN
- 0001-6322 (ISSN-L)
- 1432-0533
- OpenAlex
- W2803442844
- Cited by
- 270
- References
- 115
- Citations by year
- 2026: 18 · 2025: 34 · 2024: 57 · 2023: 39 · 2022: 29 · 2021: 40 · 2020: 29 · 2019: 20 · 2018: 4
- FWCI
- 2.28
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Acta Neuropathologica (publishedVersion)
- PubMed (publishedVersion)
- CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion)
- Padua Research Archive (University of Padova) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Keywords
- gut microbiota, intestinal barrier, neurodegenerative diseases, Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, multiple sclerosis, gastrointestinal dysfunction, enteric nervous system, intestinal epithelium
- MeSH terms
- Gastrointestinal Microbiome, Animals, Humans, Intestinal Mucosa, Enteric Nervous System, Neurodegenerative Diseases
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