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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
  1. Bruce R Stevens1,2,
  2. Ruby Goel1,
  3. Kim Seungbum1,
  4. Elaine M Richards1,
  5. Richard C Holbert2,
  6. Carl J Pepine3,
  7. Mohan K Raizada1
  1. 1 Department of Physiology & Functional Genomics, University of Florida College of Medicine, Gainesville, Florida, USA
  2. 2 Department of Psychiatry, University of Florida College of Medicine, Gainesville, Florida, USA
  3. 3 Division of Cardiovascular Medicine, University of Florida College of Medicine, Gainesville, Florida, USA
  1. Correspondence to Dr Bruce R Stevens, Department of Physiology & Functional Genomics, University of Florida College ofMedicine, 32610-0274, Gainesville, Florida, USA; stevensb{at}

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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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  • Contributors BRS and MKR had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: BRS, MKW, CJP. Acquisition, analysis, interpretation of data: BRS, MKR, KS, EMR, RG, RCH. Drafting of the manuscript: BRS, MKR, CJP. Critical revision of the manuscript: BRS, MKW, CJP, KS, EMR, RCH. Statistical analysis: BRS, EMR. Obtained funding: BRS, MKR, CJP. Administrative, technical or material support: EMR, KS, CJP. Study supervision: BRS.

  • Funding University of Florida Clinical and Translational Science Institute grant (BRS, CJP) from the National Center For Advancing Translational Sciences of the National Institutes of Health under Award Number UL1TR001427; National Institute of Health (NIH) grants HL33610, HL56921 (MKR, CJP); UM1 HL087366 (CJP); Gatorade Trust through funds distributed by the University of Florida, Department of Medicine (CJP); PCORI-OneFlorida Clinical Research Consortium CDRN-1501-26692 (CJP); and internal funds from the University of Florida Department of Physiology and Functional Genomics (BRS, MKR).

  • Disclaimer The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

  • Competing interests None declared.

  • Patient consent Detail has been removed from this case description/these case descriptions to ensure anonymity. The editors and reviewers have seen the detailed information available and are satisfied that the information backs up the case the authors are making.

  • Ethics approval The University of Florida Institutional Review Board approved the study.

  • Provenance and peer review Not commissioned; internally peer reviewed.

  • Data sharing statement Unpublished data may be accessed from the authors.

  • Correction notice This article has been corrected since it was published Online First. Figure 2 has been replaced.

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