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Cited by 125Barrier Structure and Function StudiesGut microbiota and healthAlzheimer's disease research and treatments

Gut microbiota regulates blood‐cerebrospinal fluid barrier function and Aβ pathology

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Xie, Junhua, Bruggeman, Arnout, De Nolf, Clint, Vandendriessche, Charysse, Van Imschoot, Griet, Van Wonterghem, Elien, Vereecke, Lars, Vandenbroucke, Roosmarijn E·2023·The EMBO Journal
DOI 10.15252/embj.2022111515PMC PMC10476279
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Abstract

Accumulating evidence indicates that gut microbiota dysbiosis is associated with increased blood–brain barrier (BBB) permeability and contributes to Alzheimer's disease (AD) pathogenesis. In contrast, the influence of gut microbiota on the blood‐cerebrospinal fluid (CSF) barrier has not yet been studied. Here, we report that mice lacking gut microbiota display increased blood‐CSF barrier permeability associated with disorganized tight junctions (TJs), which can be rescued by recolonization with gut microbiota or supplementation with short‐chain fatty acids (SCFAs). Our data reveal that gut microbiota is important not only for the establishment but also for the maintenance of a tight barrier. Also, we report that the vagus nerve plays an important role in this process and that SCFAs can independently tighten the barrier. Administration of SCFAs in App NL‐G‐F mice improved the subcellular localization of TJs at the blood‐CSF barrier, reduced the β‐amyloid (Aβ) burden, and affected microglial phenotype. Altogether, our results suggest that modulating the microbiota and administering SCFAs might have therapeutic potential in AD via blood‐CSF barrier tightening and maintaining microglial activity and Aβ clearance.

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  • Microbial metabolites such as SCFAs (butyrate, propionate), typically produced by Faecalibacterium prausnitzii and Roseburia, are reduced in AD, diminishing their neuroprotective effects on microglia and neuronal plasticity.

    “In parallel, microbial metabolites such as short-chain fatty acids (SCFAs, e.g., butyrate, propionate), typically produced by Faecalibacterium prausnitzii and Roseburia, are reduced in AD, thereby diminishing their neuroprotective effects on microglia and neuronal plasticity [127].”

    From Toward a Unified Framework in Molecular Neurobiology of Alzheimer’s Disease: Revisiting the Pathophysiological Hypotheses (2026) · cites this paper as [127]

    The Results section (page not provided) reports lower fecal propionate and butyrate in App NL-G-F mice than in wild-type mice, and increased microglial Aβ internalization after SCFA treatment. It does not identify Faecalibacterium prausnitzii or Roseburia as their producers or establish reduced neuronal plasticity in AD; the Results instead report similar synaptic puncta in treated and untreated AD-model mice. (LLM, conf=0.88)

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Cited by

Sorted by citations

Authors
Xie, J., Bruggeman, A., De Nolf, C., Vandendriessche, C., Van Imschoot, G., Van Wonterghem, E., Vereecke, L., & Vandenbroucke, R. E.
Affiliations
  • Ghent University (BE)
  • Ghent University Hospital (BE)
Corresponding author
Vandenbroucke, Roosmarijn E
ORCID
Venue
The EMBO Journal
Publisher
Springer Science and Business Media LLC
Published
2023-07-10
Volume
42
Issue
17
Pages
e111515-e111515
ISSN
  • 0261-4189 (ISSN-L)
  • 1460-2075
DOI
10.15252/embj.2022111515
PMC
PMC10476279
OpenAlex
W4383711104
Cited by
125
References
13
Citations by year
2026: 40 · 2025: 47 · 2024: 37 · 2023: 1
FWCI
12.51
Type
journal article
Language
en
Open access
Licence
Locations
  • The EMBO Journal (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Ghent University Academic Bibliography (Ghent University) (submittedVersion, cc-by)
Funders
  • China Scholarship Council (201808360194)
  • Fonds Baillet Latour
  • Fonds Wetenschappelijk Onderzoek (G055121N, 11M3322N)
  • Foundation for Alzheimers Research (SAO) Belgium (20190028, 20200032)
Topics
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Keywords
gut microbiota, blood-CSF barrier, blood-brain barrier permeability, Alzheimer's disease, amyloid-beta pathology, short-chain fatty acids, tight junctions, vagus nerve, microglial phenotype, gut-brain axis
MeSH terms
Gastrointestinal Microbiome, Alzheimer Disease, Animals, Blood-Brain Barrier, Fatty Acids, Volatile, Amyloid beta-Peptides, Mice, Microbiota

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