Increased human intestinal barrier permeability plasma biomarkers zonulin and FABP2 correlated with plasma LPS and altered gut microbiome in anxiety or depression

Stevens, Bruce R; Goel, Ruby; Seungbum, Kim; Richards, Elaine M; Holbert, Richard C; Pepine, Carl J; Raizada, Mohan K

doi:10.1136/gutjnl-2017-314759

Cited by 510Gut microbiota and healthGastrointestinal motility and disordersInflammatory Bowel Disease

Increased human intestinal barrier permeability plasma biomarkers zonulin and FABP2 correlated with plasma LPS and altered gut microbiome in anxiety or depression

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Stevens, Bruce R, Goel, Ruby, Seungbum, Kim, Richards, Elaine M, Holbert, Richard C, Pepine, Carl J, Raizada, Mohan K·2018·Gut

DOI 10.1136/gutjnl-2017-314759PMC PMC5851874

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Abstract

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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Barrier breakdown may contribute to MDD-associated elevations in circulating bacteria-derived compounds such as LPS, which is recognized by TLR4 on PBMCs that trigger pro-inflammatory cytokine production.
“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]
The paper reports significantly elevated plasma LPS and gut-barrier biomarkers in a combined depressive-disorder/anxiety-disorder group versus controls, and proposes a link between compromised barrier integrity and LPS entering plasma (main text, Figure 2 discussion and study description; page unavailable). It does not establish elevated LPS specifically in MDD. The TLR4/PBMC mechanism is attached to a different citation in the citing sentence, so it is not judged here. (LLM, conf=0.86)
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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 controls.
“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]
The results passage (page not provided) reports significantly elevated plasma LPS and zonulin in the DEP/ANX group versus controls. The methods passage defines that group as people with either a depressive or an anxiety disorder; the paper does not report this comparison for people with depressive disorders alone. (LLM, conf=0.88)
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The microbiome and host behavior
Vuong, H. E., Yano, J. M., Fung, T. C., & Hsiao, E. Y. (2017) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-072116-031347 · Cited by 537 · see citing works
Zonulin, a regulator of epithelial and endothelial barrier functions, and its involvement in chronic inflammatory diseases
Sturgeon, C., & Fasano, A. (2016) · Tissue Barriers · doi:10.1080/21688370.2016.1251384 · Cited by 497 · see citing works
Dose-dependent effects of endotoxin on neurobehavioral functions in humans
Grigoleit, J.-S., Kullmann, J. S., Wolf, O. T., Hammes, F., Wegner, A., Jablonowski, S., Engler, H., Gizewski, E., Oberbeck, R., & Schedlowski, M. (2011) · PLoS ONE · doi:10.1371/journal.pone.0028330 · Cited by 241 · see citing works
Intestinal cell damage and systemic immune activation in individuals reporting sensitivity to wheat in the absence of coeliac disease
Uhde, M., Ajamian, M., Caio, G., GIORGIO, R. D., Indart, A. C., Green, P. H., Verna, E. C., Volta, U., & Alaedini, A. (2016) · Gut · doi:10.1136/gutjnl-2016-311964 · Cited by 232 · see citing works
Biomarkers of Environmental Enteropathy, Inflammation, Stunting, and Impaired Growth in Children in Northeast Brazil
Guerrant, R. L., Leite, Á. M., Pinkerton, R., de Medeiros, P. H. Q. S., Cavalcante, P. A., DeBoer, M. D., Kosek, M. N., Duggan, C., Gewirtz, A. T., Kagan, J. C., et al. (2016) · PLoS ONE · doi:10.1371/journal.pone.0158772 · Cited by 216 · see citing works
Mood disturbance during experimental endotoxemia: Predictors of state anxiety as a psychological component of sickness behavior
Lasselin, J., Elsenbruch, S., Lekander, M., Axelsson, J., Karshikoff, B., Grigoleit, J., Engler, H., Schedlowski, M., & Benson, S. (2016) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2016.01.003 · Cited by 106 · see citing works

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Salvia miltiorrhiza and ischemic diseases.
Ji, X., Tan, B. K., & Zhu, Y. Z. (2000) · PubMed · Cited by 242 · see citing works
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Moulton, C. D., Pavlidis, P., Norton, C. S., Norton, S., Pariante, C. M., Hayee, B., & Powell, N. (2019) · Clinical & Experimental Immunology · doi:10.1111/cei.13276 · Cited by 102 · see citing works
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Tan, C., Yan, Q., Ma, Y., Fang, J., & Yang, Y. (2022) · Frontiers in Neurology · doi:10.3389/fneur.2022.1015175 · Cited by 111 · see citing works
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Hu, W., Kong, X., Wang, H., Li, Y., & Luo, Y. (2022) · European journal of medical research · doi:10.1186/s40001-022-00691-2 · Cited by 100 · see citing works
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Sauer, A. K., Bockmann, J., Steinestel, K., Boeckers, T. M., & Grabrucker, A. M. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20092134 · Cited by 98 · see citing works
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Self-citation
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Shieh, A., Epeldegui, M., Karlamangla, A. S., & Greendale, G. A. (2019) · JCI Insight · doi:10.1172/jci.insight.134092 · Cited by 95 · see citing works
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Chen, Y., Liang, J., Ouyang, F., Chen, X., Lu, T., Jiang, Z., Li, J., Li, Y., & Zeng, J. (2019) · Frontiers in Neurology · doi:10.3389/fneur.2019.00661 · Cited by 94 · see citing works
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Tomaz, V. D. S., Filho, A. J. M. C., Cordeiro, R. C., Jucá, P. M., Soares, M. V. R., Barroso, P. N., Cristino, L. M. F., Jiang, W., Teixeira, A. L., de Lucena, D. F., et al. (2020) · Journal of Affective Disorders · doi:10.1016/j.jad.2020.03.022 · Cited by 90 · see citing works
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Navarro‐Tapia, E., Almeida-Toledano, L., Sebastiani, G., Serra-Delgado, M., García‐Algar, Ó., & Andreu-Férnández, V. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22052351 · Cited by 91 · see citing works
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Veres-Székely, A., Szász, C., Pap, D., Szebeni, B., Bokrossy, P., & Vannay, Á. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24087548 · Cited by 88 · see citing works
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Álvarez-Mon, M. Á., Gomez-Lahoz, A. M., Orozco, A., Lahera, G., Sosa-Reina, M. D., Díaz, D., Aubá, E., Albillos, A., Monserrat, J., & Álvarez‐Mon, M. (2019) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2019.00812 · Cited by 86 · see citing works
Serum zonulin and its diagnostic performance in non-coeliac gluten sensitivity
Barbaro, M. R., Cremon, C., Morselli‐Labate, A. M., Sabatino, A. D., Giuffrida, P., Corazza, G. R., Stefano, M. D., Caio, G., Latella, G., Ciacci, C., et al. (2020) · Gut · doi:10.1136/gutjnl-2019-319281 · Cited by 88 · see citing works
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Chang, Z., Liu, H.-M., Leu, Y., Hsu, C.-H., & Lee, T.-Y. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23052667 · Cited by 89 · see citing works
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Ma, Y., Liu, T., Fu, J., Fu, S.-L., Hu, C., Sun, B., Fan, X., & Zhu, J. (2019) · Journal of Nutrition · doi:10.1093/jn/nxz105 · Cited by 86 · see citing works
Crosstalk between gut microbiota and host immune system and its response to traumatic injury
Ullah, H., Arbab, S., Tian, Y., Chen, Y., Liu, C., Li, Q., & Li, K. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1413485 · Cited by 93 · see citing works
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Wang, K., Yang, X., Wu, Z.-J., Wang, H., Li, Q., Mei, H., You, R., & Zhang, Y. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.00240 · Cited by 85 · see citing works
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Muralitharan, R. R., Zheng, T., Dinakis, E., Xie, L., Barbaro-Wahl, A., Jama, H. A., Nakai, M. E., Patterson, M., Leung, K. C., McArdle, Z. M., et al. (2025) · Circulation Research · doi:10.1161/circresaha.124.325770 · Cited by 88 · see citing works
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Lv, W., Liu, C., Yu, L., Zhou, J., Li, Y., Xiong, Y., Guo, A., Chao, L., Qu, Q., Guang-wei, W., et al. (2020) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2020/1241894 · Cited by 85 · see citing works
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Sauer, A. K., & Grabrucker, A. M. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.01295 · Cited by 85 · see citing works
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Chen, Y.-H., Xue, F., Yu, S.-F., Li, X.-S., Liu, L., Jia, Y., Yan, W., Tan, Q.-R., Wang, H., & Peng, Z. (2020) · Journal of Affective Disorders · doi:10.1016/j.jad.2020.12.143 · Cited by 80 · see citing works
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Malan‐Müller, S., Valles‐Colomer, M., Foxx, C. L., Vieira‐Silva, S., van den Heuvel, L. L., Raes, J., Seedat, S., Lowry, C. A., & Hemmings, S. M. J. (2021) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2021.11.009 · Cited by 81 · see citing works
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Prasad, R., Patton, M. J., Floyd, J. L., Vieira, C. P., Fortmann, S., DuPont, M., Harbour, A., Jeremy, C. S., Wright, J., Lamendella, R., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23169141 · Cited by 78 · see citing works
Self-citation
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Audet, M. (2019) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2019.100772 · Cited by 79 · see citing works
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Biomarkers of intestinal permeability and blood-brain barrier permeability in adolescents with major depressive disorder
Wu, H., Wang, J., Teng, T., Yin, B., He, Y., Jiang, Y., Liu, X., Yu, Y., Li, X., & Zhou, X. (2022) · Journal of Affective Disorders · doi:10.1016/j.jad.2022.11.058 · Cited by 74 · see citing works
Psychophysiological Effects of Lactobacillus plantarum PS128 in Patients with Major Depressive Disorder: A Preliminary 8-Week Open Trial
Chen, H., Kuo, P., Hsu, C., Chiu, Y.-H., Liu, Y.-W., Lu, M., & Chen, C.-H. (2021) · Nutrients · doi:10.3390/nu13113731 · Cited by 78 · see citing works
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Zhou, B., Jin, G., Pang, X., Mo, Q., Bao, J., Liu, T., Wu, J., Xie, R., Liu, X., Liu, J., et al. (2022) · Pharmacological Research · doi:10.1016/j.phrs.2022.106090 · Cited by 77 · see citing works
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Zeb, F., Osaili, T. M. I., Obaid, R. S., Naja, F., Radwan, H. M., Ismail, L. C., Hasan, H. A., Hashim, M. S., Alam, I., Sehar, B., et al. (2023) · Nutrients · doi:10.3390/nu15020259 · Cited by 73 · see citing works
Does Anxiety Increase the Risk of all-Cause Dementia? An Updated Meta-Analysis of Prospective Cohort Studies
Santabárbara, J., Lipnicki, D. M., Olaya, B., Villagrasa, B., Bueno‐Notivol, J., Nuez, L., López‐Antón, R., & Gracia‐García, P. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9061791 · Cited by 74 · see citing works
The gut microbiota promotes the pathogenesis of schizophrenia via multiple pathways
Yuan, X., Kang, Y., Zhuo, C., Huang, X., & Song, X. (2019) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2019.02.152 · Cited by 73 · see citing works
Microbiota‐microglia connections in age‐related cognition decline
Zhou, R., Qian, S., Cho, W. C. S., Zhou, J., Jin, C., Zhong, Y., Wang, J., Zhang, X., Xu, Z., Tian, M., et al. (2022) · Aging Cell · doi:10.1111/acel.13599 · Cited by 71 · see citing works
Molecular Basis Underlying the Therapeutic Potential of Vitamin D for the Treatment of Depression and Anxiety
Kouba, B. R., Camargo, A., Gil‐Mohapel, J., & Rodrigues, A. L. S. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23137077 · Cited by 77 · see citing works
Depression phenotype identified by using single nucleotide exact amplicon sequence variants of the human gut microbiome
Stevens, B. R., Roesch, L. F. W., Dobbler, P. T., Russell, J. T., Pepine, C. J., Holbert, R. C., Raizada, M. K., & Triplett, E. W. (2020) · Molecular Psychiatry · doi:10.1038/s41380-020-0652-5 · Cited by 70 · see citing works
Self-citation
The gut microbiota metabolite indole increases emotional responses and adrenal medulla activity in chronically stressed male mice
Mir, H.-D., Milman, A., Monnoye, M., Douard, V., Philippe, C., Aubert, A., Castanon, N., Vancassel, S., Guérineau, N. C., Naudon, L., et al. (2020) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2020.104750 · Cited by 70 · see citing works
Gut microbiome and thyroid autoimmunity
Virili, C., Stramazzo, I., & Centanni, M. (2021) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2021.101506 · Cited by 69 · see citing works
Bacterial Extracellular Vesicles and the Gut‐Microbiota Brain Axis: Emerging Roles in Communication and Potential as Therapeutics
Pirolli, N. H., Bentley, W. E., & Jay, S. M. (2021) · Advanced Biology · doi:10.1002/adbi.202000540 · Cited by 70 · see citing works
Metabolomic Biomarkers in Anxiety Disorders
Humer, E. C., Pieh, C., & Probst, T. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21134784 · Cited by 68 · see citing works

Intestinal microbiota, probiotics and mental health: from Metchnikoff to modern advances: Part II – contemporary contextual research
Bested, A. C., Logan, A. C., & Selhub, E. M. (2013) · Gut Pathogens · doi:10.1186/1757-4749-5-3 · Cited by 121 · see citing works
Microbiota intestinal y su relación con la salud mental. Una revisión narrativa
Orbe-Orihuela, C., Hernández Mariano, J. Á., Castañeda-Márquez, A. C., & Alvarado Delgado, A. (2024) · Dialnet (Universidad de la Rioja)
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Villela, E. V., Cruz, I. D. F., Campos, M. S., & Vardiero, H. A. (2024) · International Journal of Health Science · doi:10.22533/at.ed.1594752412089
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Lal, K. K., & Verma, R. (2025) · doi:10.70593/978-93-7185-482-5_1
Systematic review: Association between gut microbiota and mental health
da Silva, B. H. (2024) · International Seven Journal of Health Research · doi:10.56238/isevjhv3n1-019

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
ORCID: Stevens, Bruce R
Goel, Ruby
Richards, Elaine M
Pepine, Carl J
Raizada, Mohan K
Venue: Gut
Publisher: BMJ
Published: 2017-08-16
Volume: 67
Issue: 8
Pages: 1555.2-1557
ISSN: 0017-5749 (ISSN-L)
1468-3288
DOI: 10.1136/gutjnl-2017-314759
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
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › 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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Increased human intestinal barrier permeability plasma biomarkers zonulin and FABP2 correlated with plasma LPS and altered gut microbiome in anxiety or depression

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