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Increased human intestinal barrier permeability plasma biomarkers zonulin and FABP2 correlated with plasma LPS and altered gut microbiome in anxiety or depression
Open accessAbstract
We read with interest the recent work by Uhde et al ,1 which demonstrated that physically asymptomatic non-coeliac gluten/wheat sensitivity involves compromised intestinal epithelium barrier dysfunction in conjunction with systemic immune activation events. We also read with interest the recent work by Marchesi et al ,2 which comprehensively reviewed the role of microbiota in physical disorders of the gut and extra-gut organs. But common to these Gut papers was the lack of accounting for anxiety and depression, comorbidities often experienced in gastroenterology clinics. Patients who are otherwise physically asymptomatic often do not explicitly divulge these mental disorders, or the disorders are unintentionally overlooked, yet they report ‘diminished quality of life’. In response to this gap, we explored roles of dysbiosis and gut barrier integrity in individuals physically asymptomatic for gastrointestinal distress, yet nonetheless experiencing mental distress. We hypothesised that anxiety and depressive disorders are linked to human gut dysbiosis with microbiota that secrete lipopolysaccharide (LPS) endotoxin into plasma, which in conjunction with compromised gut barrier integrity has systemic manifestations including the brain. We further hypothesised that this correlates with altered intestinal epithelium paracellular integrity molecules discharged …
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“This may contribute to the MDD-associated elevations in circulating bacteria-derived compounds (such as lipopolysaccharide (LPS)108), which is recognized by toll-like receptor 4 (TLR4) on peripheral blood mononuclear cells (PBMCs) that trigger pro-inflammatory cytokine production109.”
From Central regulation of stress-evoked peripheral immune responses (2023) · cites this paper as [108]
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“plasma biomarkers of increased gut permeability, including LPS and zonulin, have been found in greater abundance in people with depressive disorders compared to healthy controls238.”
From Comorbidity between major depressive disorder and physical diseases: a comprehensive review of epidemiology, mechanisms and management (2023) · cites this paper as [238]
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Metadata
- Authors
- Stevens, B. R., Goel, R., Seungbum, K., Richards, E. M., Holbert, R. C., Pepine, C. J., & Raizada, M. K.
- Affiliations
- University of Florida Health (US)
- Corresponding author
- Stevens, Bruce R
- Venue
- Gut
- Publisher
- BMJ
- Published
- 2017-08-16
- Volume
- 67
- Issue
- 8
- Pages
- 1555.2-1557
- ISSN
- 0017-5749 (ISSN-L)
- 1468-3288
- PMC
- PMC5851874
- OpenAlex
- W2745400272
- Cited by
- 508
- References
- 7
- Citations by year
- 2026: 37 · 2025: 66 · 2024: 70 · 2023: 72 · 2022: 65 · 2021: 70 · 2020: 66 · 2019: 37 · 2018: 19 · 2017: 4
- FWCI
- 14.00
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Gut (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- PCORI-OneFlorida Clinical Research Consortium
- National Institutes of Health
- Gatorade Trust through funds distributed by the University of Florida, Department of Medicine
- University of Florida Department of Physiology and Functional Genomics
- University of Florida Clinical and Translational Science Institute grant from the National Center For Advancing Translational Sciences of the National Institutes of Health
- 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 › Gastroenterology › Inflammatory Bowel Disease
- Keywords
- intestinal permeability, zonulin, FABP2, lipopolysaccharide, gut dysbiosis, gut microbiota, anxiety, depression, non-celiac gluten sensitivity, wheat sensitivity, plasma biomarkers, endotoxin
- MeSH terms
- Gastrointestinal Microbiome, Anxiety, Cholera Toxin, Depression, Haptoglobins, Humans, Intestines, Permeability, Protein Precursors, Biomarkers, Fatty Acid-Binding Proteins
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