The intestinal barrier in disorders of the central nervous system
Open accessAbstract
The intestinal barrier, which primarily consists of a mucus layer, an epithelial barrier, and a gut vascular barrier, has a crucial role in health and disease by facilitating nutrient absorption and preventing the entry of pathogens. The intestinal barrier is in close contact with gut microbiota on its luminal side and with enteric neurons and glial cells on its tissue side. Mounting evidence now suggests that the intestinal barrier is compromised not only in digestive disorders, but also in disorders of the central nervous system (CNS), such as Parkinson's disease, autism spectrum disorder, depression, multiple sclerosis, and Alzheimer's disease. After providing an overview of the structure and functions of the intestinal barrier, we review existing preclinical and clinical studies supporting the notion that intestinal barrier dysfunction is present in neurological, neurodevelopmental, and psychiatric disorders. On the basis of this evidence, we discuss the mechanisms that possibly link gut barrier dysfunction and CNS disorders and the potential impact that evaluating enteric barriers in brain disorders could have on clinical practice, in terms of novel diagnostic and therapeutic strategies, in the near future.
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During aging, the intestinal barrier undergoes progressive breakdown, facilitating the translocation of pro-inflammatory gut microbiota-derived metabolites and pathogenic bacterial products into the bloodstream.
“During aging, the intestinal barrier undergoes progressive breakdown, which facilitates the translocation of pro-inflammatory gut microbiota-derived metabolites and pathogenic bacterial products into the bloodstream”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [623]
Increased intestinal permeability facilitates the translocation of bacteria and their byproducts into the mucosa and bloodstream, leading to aberrant activation of intestinal and circulating immune and inflammatory cells, resulting in systemic inflammation, neuroinflammation, and neurodegeneration.
“the increased intestinal permeability facilitates the translocation of bacteria and their byproducts into the mucosa and bloodstream. This leads to aberrant activation of the intestinal and circulating immune and inflammatory cells, resulting in systemic inflammation, neuroinflammation, and neurodegeneration.”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [623]
This process triggers elevated systemic inflammatory responses that gradually impair BBB integrity, resulting in CNS inflammation and neurodegeneration.
“This process triggers elevated systemic inflammatory responses that gradually impair BBB integrity, resulting in CNS inflammation and neurodegeneration.”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [623]
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Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases
Loh, J. S., Mak, W. Q., Tan, L. K. S., Ng, C. X., Chan, H. H., Yeow, S. H., Foo, J. B., Ong, Y. S., How, C. W., & Khaw, K. Y. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01743-1 · Cited by 1,193 · see citing works
Understanding the Gut–Brain Axis and Its Therapeutic Implications for Neurodegenerative Disorders
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- Authors
- Pellegrini, C., Fornai, M., D'Antongiovanni, V., Antonioli, L., Bernardini, N., & Derkinderen, P.
- Affiliations
- University of Pisa (IT)
- Inserm (FR)
- Venue
- The Lancet Gastroenterology & Hepatology
- Publisher
- Elsevier BV
- Published
- 2023-01
- Volume
- 8
- Issue
- 1
- Pages
- 66-80
- ISSN
- 2468-1156 (ISSN-L)
- 2468-1253
- OpenAlex
- W4308158341
- Cited by
- 239
- References
- 124
- Citations by year
- 2026: 63 · 2025: 89 · 2024: 54 · 2023: 32 · 2022: 1
- FWCI
- 4.58
- Type
- journal article
- Language
- en
- Open access
- green
- hal.science
- Licence
- Locations
- The Lancet. Gastroenterology & hepatology (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion, other-oa)
- CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- intestinal barrier, intestinal barrier dysfunction, central nervous system disorders, Parkinson's disease, autism spectrum disorder, depression, multiple sclerosis, Alzheimer's disease, gut microbiota, enteric neurons, glial cells, gut-brain axis, neurodevelopmental disorders, mental illness, diagnostic biomarkers, treatment options
- MeSH terms
- Autism Spectrum Disorder, Gastrointestinal Microbiome, Central Nervous System, Humans, Intestinal Diseases
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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