Brain–Gut Interactions in Inflammatory Bowel Disease

Bonaz, Bruno L.; Bernstein, Charles N.

doi:10.1053/j.gastro.2012.10.003

Cited by 667Inflammatory Bowel DiseaseVagus Nerve Stimulation ResearchGastrointestinal motility and disorders

Brain–Gut Interactions in Inflammatory Bowel Disease

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Bonaz, Bruno L., Bernstein, Charles N.·2013·Gastroenterology

DOI 10.1053/j.gastro.2012.10.003

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Abstract

Psycho-neuro-endocrine-immune modulation through the brain-gut axis likely has a key role in the pathogenesis of inflammatory bowel disease (IBD). The brain-gut axis involves interactions among the neural components, including (1) the autonomic nervous system, (2) the central nervous system, (3) the stress system (hypothalamic-pituitary-adrenal axis), (4) the (gastrointestinal) corticotropin-releasing factor system, and (5) the intestinal response (including the intestinal barrier, the luminal microbiota, and the intestinal immune response). Animal models suggest that the cholinergic anti-inflammatory pathway through an anti-tumor necrosis factor effect of the efferent vagus nerve could be a therapeutic target in IBD through a pharmacologic, nutritional, or neurostimulation approach. In addition, the psychophysiological vulnerability of patients with IBD, secondary to the potential presence of any mood disorders, distress, increased perceived stress, or maladaptive coping strategies, underscores the psychological needs of patients with IBD. Clinicians need to address these issues with patients because there is emerging evidence that stress or other negative psychological attributes may have an effect on the disease course. Future research may include exploration of markers of brain-gut interactions, including serum/salivary cortisol (as a marker of the hypothalamic-pituitary-adrenal axis), heart rate variability (as a marker of the sympathovagal balance), or brain imaging studies. The widespread use and potential impact of complementary and alternative medicine and the positive response to placebo (in clinical trials) is further evidence that exploring other psycho-interventions may be important therapeutic adjuncts to the conventional therapeutic approach in IBD.

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In IBD, chronic stress and HPA dysregulation worsen intestinal inflammation through neuroendocrine-immune interactions.
“Bonaz (2013) highlighted that in IBD, chronic stress and HPA dysregulation worsen intestinal inflammation through neuroendocrine-immune interactions.”
From Chronic Stress and Autoimmunity: The Role of HPA Axis and Cortisol Dysregulation (2025) · cites this paper as [66]
The sections “Downregulation of the hypothalamic CRFergic system” and “Stress-induced brain-gut perturbations” describe neuroendocrine–immune pathways and report that chronic stress worsened experimental colitis. But the paper says a hyporeactive HPA axis in IBD *may* lead to colonic inflammation; it does not establish the claim’s unqualified causal conclusion in people with IBD. Page numbers were unavailable in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measured
Excessive sympathetic or parasympathetic activity in the ANS can lead to dysregulation within the gut-brain axis contributing to maladaptive gastrointestinal responses and resulting in symptomatic flares.
“Excessive sympathetic or parasympathetic activity in the ANS can lead to dysregulation within the gut-brain axis contributing to maladaptive gastrointestinal responses and resulting in symptomatic flares (8–12,14).”
From Alterations in Heart Rate Variability Associated With Irritable Bowel Syndrome or Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis (2021) · cites this paper as [11]
The “Vagal inhibition” section (page unavailable) says stress increases sympathetic outflow and decreases vagal, or parasympathetic, outflow, favoring intestinal inflammation. “Stress and IBD” links stress to symptomatic flares. The paper does not support the claim that excessive parasympathetic activity contributes to flares; it describes reduced parasympathetic activity instead. (LLM, conf=0.88)
Experimental — accuracy not yet measured
The interplay intensifies mucosal immune activation and disease flares.
“This interplay intensifies mucosal immune activation and disease flares, suggesting stress pathway modulation as a therapeutic target [66].”
From Chronic Stress and Autoimmunity: The Role of HPA Axis and Cortisol Dysregulation (2025) · cites this paper as [66]
Heart rate variability provides an indirect measure of the autonomic nervous system.
“Such monitoring might be achieved through a set of noninvasive electrocardiography parameters, collectively referred to as heart rate variability (HRV), that provides an indirect measure of the autonomic nervous system (ANS) (8–14).”
From Alterations in Heart Rate Variability Associated With Irritable Bowel Syndrome or Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis (2021) · cites this paper as [11]
Gut inflammation may impact mental health and therapy response given the role of the brain-gut axis in pathobiology of IBD.
“gut inflammation may impact mental health and therapy response given the role of the brain-gut axis in pathobiology of IBD (58).”
From The 2023 Impact of Inflammatory Bowel Disease in Canada: Mental Health and Inflammatory Bowel Disease (2023) · cites this paper as [58]

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Qiu, B., Vallance, B. A., Blennerhassett, P. A., & Collins, S. M. (1999) · Nature Medicine · doi:10.1038/13503 · Cited by 252 · see citing works
Corticotropin-releasing hormone mimics stress-induced colonic epithelial pathophysiology in the rat
Santos, J., Saunders, P. R., Hanssen, N. P. M., Yang, P., Yates, D. A., Groot, J. A., & Perdue, M. H. (1999) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.1999.277.2.g391 · Cited by 251 · see citing works
Gene expression analysis in the human hypothalamus in depression by laser microdissection and real-time PCR: the presence of multiple receptor imbalances
Wang, S.-S., Kamphuis, W., Huitinga, I., Zhou, J.-N., & Swaab, D. F. (2008) · Molecular Psychiatry · doi:10.1038/mp.2008.38 · Cited by 250 · see citing works
Psychological issues in inflammatory bowel disease: an overview
Sajadinejad, M. S., Asgari, K., Molavi, H., Kalantari, M., & Adibi, P. (2012) · Gastroenterology Research and Practice · doi:10.1155/2012/106502 · Cited by 242 · see citing works
Neonatal maternal deprivation triggers long term alterations in colonic epithelial barrier and mucosal immunity in rats
Barreau, F., Ferrier, L., Fioramonti, J., & Bueno, L. P. (2004) · Gut · doi:10.1136/gut.2003.024174 · Cited by 240 · see citing works
Longitudinal study of quality of life and psychological functioning for active, fluctuating, and inactive disease patterns in inflammatory bowel disease
Lix, L. M., Graff, L. A., Walker, J. R., Clara, I., Rawsthorne, P., Rogala, L., Miller, N., Ediger, J., Pretorius, T., & Bernstein, C. N. (2008) · Inflammatory Bowel Diseases · doi:10.1002/ibd.20511 · Cited by 238 · see citing works
The role of the sympathetic nervous system in intestinal inflammation
Straub, R. H., Wiest, R., Strauch, U. G., Härle, P., & Schölmerich, J. (2006) · Gut · doi:10.1136/gut.2006.091322 · Cited by 237 · see citing works
Impaired parasympathetic function increases susceptibility to inflammatory bowel disease in a mouse model of depression
Ghia, J.-E., Blennerhassett, P., & Collins, S. M. (2008) · Journal of Clinical Investigation · doi:10.1172/jci32849 · Cited by 233 · cited 1× · see citing works
“Experimental sustained depression in mice is followed by impaired parasympathetic function and increased susceptibility to an experimental colitis that was reduced by desmethylimipramine, by a vagally dependent enhanced parasympathetic function (81).”
Background
Psychosocial determinants of relapse in ulcerative colitis: A longitudinal study
Bitton, A., Sewitch, M. J., Peppercorn, M. A., de B Edwardes, M. D., Shah, S., Ransil, B., & Locke, S. E. (2003) · American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2003.07717.x · Cited by 226 · see citing works
Activation of the Cholinergic Anti-Inflammatory Pathway Ameliorates Postoperative Ileus in Mice
The, F. O., Boeckxstaens, G. E., Snoek, S. A., Cash, J. L., Bennink, R. J., LaRosa, G. J., van den Wijngaard, R. M., Greaves, D. R., & de Jonge, W. J. (2007) · Gastroenterology · doi:10.1053/j.gastro.2007.07.022 · Cited by 226 · see citing works
Physiological and pathophysiological functions of intestinal mast cells
Bischoff, S. C. (2009) · Seminars in Immunopathology · doi:10.1007/s00281-009-0165-4 · Cited by 225 · see citing works
Human psychoneuroimmunology: 20 Years of discovery
Irwin, M. R. (2007) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2007.07.013 · Cited by 225 · see citing works
Stress stimulates transepithelial macromolecular uptake in rat jejunum
Kiliaan, A. J., Saunders, P. R., Bijlsma, P. B., Berin, M. C., Taminiau, J. A., Groot, J. A., & Perdue, M. H. (1998) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.1998.275.5.g1037 · Cited by 223 · see citing works
CRF induces intestinal epithelial barrier injury via the release of mast cell proteases and TNF-α
Overman, E. L., Rivier, J. E., & Moeser, A. J. (2012) · PLoS ONE · doi:10.1371/journal.pone.0039935 · Cited by 207 · see citing works
Impaired Synthesis or Cellular Storage of Norepinephrine, Dopamine, and 5-Hydroxytryptamine in Human Inflammatory Bowel Disease
Magro, F., Vieira‐Coelho, M. A., Fraga, S., Serrão, P., Veloso, F. T., Ribeiro, T., & Soares-da-Silva, P. (2002) · Digestive Diseases and Sciences · doi:10.1023/a:1013256629600 · Cited by 206 · see citing works
Autonomy of Autonomic Dysfunction in Major Depression
Koschke, M., Boettger, M. K., Schulz, S., Berger, S., Terhaar, J., Voss, A., Yeragani, V. K., & Bär, K.-J. (2009) · Psychosomatic Medicine · doi:10.1097/psy.0b013e3181b8bb7a · Cited by 199 · see citing works
Factors affecting health related quality of life of patients with inflammatory bowel disease
Casellas, F., López-Vivancos, J., Casado, A., & Malagelada, J. (2002) · Quality of Life Research · doi:10.1023/a:1020841601110 · Cited by 198 · see citing works
Psychological adjustment and autonomic disturbances in inflammatory bowel diseases and irritable bowel syndrome
Pellissier, S., Dantzer, C., Canini, F., Mathieu, N., & Bonaz, B. (2010) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2009.10.004 · Cited by 198 · see citing works
Self-citation
The Role of Stress in the Development and Clinical Course of Inflammatory Bowel Disease: Epidemiological Evidence
Maunder, R., & Levenstein, S. (2008) · Current Molecular Medicine · doi:10.2174/156652408784533832 · Cited by 198 · see citing works
Chronic interpersonal stress predicts activation of pro- and anti-inflammatory signaling pathways 6 months later
Miller, G. E., Rohleder, N., & Cole, S. W. (2009) · Psychosomatic Medicine · doi:10.1097/psy.0b013e318190d7de · Cited by 197 · see citing works
Maternal Deprivation in Rats is Associated with Corticotrophin‐Releasing Hormone (CRH) Promoter Hypomethylation and Enhances CRH Transcriptional Responses to Stress in Adulthood
Chen, J., Evans, A. N., Liu, Y., Honda, M., Saavedra, J. M., & Aguilera, G. (2012) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2012.02306.x · Cited by 193 · see citing works
Psychological Distress, Social Support, and Disease Activity in Patients With Inflammatory Bowel Disease
Sewitch, M. J., Abrahamowicz, M., Bitton, A., Daly, D., Wild, G. E., Cohen, A., Katz, S., Szego, P. L., & Dobkin, P. L. (2001) · American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2001.03800.x · Cited by 192 · see citing works
Comorbidity of physical and mental disorders and the effect on work-loss days
Buist‐Bouwman, M. A., de Graaf, R., Vollebergh, W. A. M., & Ormel, J. (2005) · Acta Psychiatrica Scandinavica · doi:10.1111/j.1600-0447.2005.00513.x · Cited by 189 · see citing works
Perceptual responses in patients with inflammatory and functional bowel disease
Chang, L., Munakata, J., Mayer, E. A., Schmulson, M. J., Johnson, T. D., Bernstein, C. N., Saba, L., Naliboff, B., Anton, P. A., & Matin, K. (2000) · Gut · doi:10.1136/gut.47.4.497 · Cited by 185 · see citing works
Self-citation
Psychiatric diagnoses, sexual and physical victimization, and disability in patients with irritable bowel syndrome or inflammatory bowel disease
Walker, E. A., Gelfand, A. N., Gelfand, M. D., & Katon, W. J. (1995) · Psychological Medicine · doi:10.1017/s0033291700033225 · Cited by 181 · see citing works
Rectal afferent function in patients with inflammatory and functional intestinal disorders
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Self-citation
Bidirectional interaction between the central nervous system and the immune system
Rabin, B. S., Cohen, S., Ganguli, R., Lysle, D. T., & Cunnick, J. E. (2018) · PubMed · doi:10.1184/r1/6613715 · Cited by 171 · see citing works
Irritable bowel syndrome: a model of the brain-gut interactions.
Mulak, A., & Bonaz, B. L. (2004) · PubMed · Cited by 161 · see citing works
Self-citation
Effects of chemical sympathectomy and sensory nerve ablation on experimental colitis in the rat
McCafferty, D., Wallace, J. L., & Sharkey, K. A. (1997) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.1997.272.2.g272 · Cited by 152 · see citing works
Depressive symptoms enhance stress-induced inflammatory responses.
Fagundes, C. P., Glaser, R., Hwang, B. S., Malarkey, W. B., & Kiecolt-Glaser, J. K. (2013) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2012.05.006 · Cited by 151 · see citing works
Stress-induced enhancement of colitis in rats: CRF and arginine vasopressin are not involved
Gué, M., Bonbonne, C., Fioramonti, J., Moré, J., Rio-Lacheze, C. D., Coméra, C., & Bueno, L. P. (1997) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.1997.272.1.g84 · Cited by 148 · see citing works
CRF receptor type 1 and 2 expression and anatomical distribution in the rat colon
Chatzaki, Ε., Crowe, P. D., Wang, L., Million, M., Taché, Y., & Grigoriadis, D. E. (2004) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2004.02490.x · Cited by 146 · see citing works
The relationship of current psychiatric disorder to functional disability and distress in patients with inflammatory bowel disease
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The Effect of Acute Psychologic Stress on Systemic and Rectal Mucosal Measures of Inflammation in Ulcerative Colitis
Mawdsley, J. E., Macey, M. G., Feakins, R. M., Langmead, L., & Rampton, D. S. (2006) · Gastroenterology · doi:10.1053/j.gastro.2006.05.017 · Cited by 143 · see citing works
Heart rate variability, overnight urinary norepinephrine and C‐reactive protein: evidence for the cholinergic anti‐inflammatory pathway in healthy human adults
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Vagus Nerve Stimulation for Epilepsy and Depression
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Predictors of Quality of Life in Ulcerative Colitis.
Han, S. W., McColl, E., Barton, J. R., James, P., Steen, I. N., & Welfare, M. (2005) · Inflammatory Bowel Diseases · doi:10.1097/00054725-200501000-00004 · Cited by 140 · see citing works
A Prospective Study of the Relationship between Disease Activity and Psychologic Distress in Patients with Inflammatory Bowel Disease
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“Alternatively, two studies found that higher levels of depression and anxiety during an active disease phase dropped with improvement in IBD (95, 106).”
Background
Neonatal maternal separation causes colonic dysfunction in rat pups including impaired host resistance
Gareau, M. G., Jury, J., Yang, P. C., MacQueen, G., & Perdue, M. H. (2006) · Pediatric Research · doi:10.1203/01.pdr.0000190577.62426.45 · Cited by 139 · see citing works
Corticotropin-releasing factor signaling and visceral response to stress
Stengel, A., & Taché, Y. (2010) · Experimental Biology and Medicine · doi:10.1258/ebm.2010.009347 · Cited by 139 · see citing works
The Manitoba Inflammatory Bowel Disease Cohort Study: Prolonged Symptoms Before Diagnosis—How Much Is Irritable Bowel Syndrome?
Burgmann, T., Clara, I., Graff, L., Walker, J., Lix, L., Rawsthorne, P., McPhail, C., Rogala, L., Miller, N., & Bernstein, C. N. (2006) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2006.03.003 · Cited by 135 · see citing works
Self-citation
Health-related quality of life in Crohn's disease: a prospective longitudinal study in 231 patients.
Blondel-Kucharski, F., Chircop, C., Marquis, P., Cortot, A., Baron, F., Jp, G., & Colombel, J. (2001) · PubMed · doi:10.1111/j.1572-0241.2001.4681_b.x · Cited by 134 · see citing works
Stress induces the translocation of cutaneous and gastrointestinal microflora to secondary lymphoid organs of C57BL/6 mice
Bailey, M. T., Engler, H., & Sheridan, J. F. (2006) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2005.09.008 · Cited by 133 · see citing works
Preliminary evidence supporting a framework of psychological adjustment to inflammatory bowel disease†
Kiebles, J. L., Doerfler, B., & Keefer, L. (2010) · Inflammatory Bowel Diseases · doi:10.1002/ibd.21215 · Cited by 132 · see citing works
Do Antidepressants Influence the Disease Course in Inflammatory Bowel Disease? A Retrospective Case‐Matched Observational Study
Goodhand, J., Greig, F. I. S., Koodun, Y., Mcdermott, A., Wahed, M., Langmead, L., & Rampton, D. (2012) · Inflammatory Bowel Diseases · doi:10.1002/ibd.21846 · Cited by 131 · see citing works
Tai Chi Chih acutely decreases sympathetic nervous system activity in older adults.
Motivala, S. J., Sollers, J., Thayer, J., & Irwin, M. R. (2006) · The journals of gerontology. Series A, Biological sciences and medical sciences · doi:10.1093/gerona/61.11.1177 · Cited by 128 · see citing works
Common Symptoms and Stressors Among Individuals With Inflammatory Bowel Diseases
Singh, S. R. K., Blanchard, A. K., Walker, J. R., Graff, L. A., Miller, N., & Bernstein, C. N. (2011) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2011.05.016 · Cited by 128 · see citing works
Self-citation
Antidepressants Attenuate Increased Susceptibility to Colitis in a Murine Model of Depression
Varghese, A. K., Verdu, E. F., Berčík, P., Khan, W. I., Blennerhassett, P. A., Szechtman, H., & Collins, S. M. (2006) · Gastroenterology · doi:10.1053/j.gastro.2006.02.007 · Cited by 128 · see citing works
Susceptibility of Lewis and Fischer rats to stress-induced worsening of TNB-colitis: protective role of brain CRF
Million, M., Taché, Y., & Anton, P. (1999) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.1999.276.4.g1027 · Cited by 128 · see citing works
Stress Coping, Distress, and Health Perceptions in Inflammatory Bowel Disease and Community Controls
Graff, L. A., Walker, J. R., Clara, I. P., Lix, L. M., Miller, N., Rogala, L., Rawsthorne, P. E., & Bernstein, C. N. (2009) · The American Journal of Gastroenterology · doi:10.1038/ajg.2009.529 · Cited by 126 · see citing works
Self-citation
Antidepressants and inflammatory bowel disease: a systematic review.
Mikocka‐Walus, A. A., Turnbull, D. A., Moulding, N., Wilson, I. G., Andrews, J. M., & Holtmann, G. (2006) · Clinical Practice and Epidemiology in Mental Health · doi:10.1186/1745-0179-2-24 · Cited by 120 · see citing works
Health-related quality of life in Crohn’s disease: a prospective longitudinal study in 231 patients
Blondel-Kucharski, F., Chircop, C., Marquis, P., Cortot, A., Baron, F., Gendre, J.-P., Colombel, J.-F., & (GETAID), T. G. D. T. D. A. I. D. (2001) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2001.04681.x · Cited by 120 · see citing works
Chronic stress-induced cellular changes in the medial prefrontal cortex and their potential clinical implications: Does hemisphere location matter?
Czéh, B., Perez‐Cruz, C., Fuchs, E., & Flügge, G. (2008) · Behavioural Brain Research · doi:10.1016/j.bbr.2008.02.031 · Cited by 117 · see citing works
The Role of Psychological Stress in Inflammatory Bowel Disease
Mawdsley, J. E. D., & Rampton, D. S. (2006) · NeuroImmunoModulation · doi:10.1159/000104861 · Cited by 116 · see citing works
Uncoupling of the sympathetic nervous system and the hypothalamic–pituitary–adrenal axis in inflammatory bowel disease?
Straub, R. H., Herfarth, H., Falk, W., Andus, T., & Schölmerich, J. (2002) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(02)00047-4 · Cited by 115 · see citing works
Increase of sympathetic outflow measured by neuropeptide Y and decrease of the hypothalamic-pituitary-adrenal axis tone in patients with systemic lupus erythematosus and rheumatoid arthritis: another example of uncoupling of response systems
Härle, P., Straub, R. H., Wiest, R., Mayer, A., Schölmerich, J., Atzeni, F., Carrabba, M., Cutolo, M., & Sarzi-Puttini, P. (2006) · Annals of the Rheumatic Diseases · doi:10.1136/ard.2005.038059 · Cited by 114 · see citing works
Effect of a chronic stress on CRF neuronal activity and expression of its type 1 receptor in the rat brain
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The relationships among heart rate variability, inflammatory markers and depression in coronary heart disease patients
Frasure‐Smith, N., Lespérance, F., Irwin, M. R., Talajic, M. R., & Pollock, B. G. (2009) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2009.07.005 · Cited by 110 · see citing works
Cytokine-Induced Alterations of α7 Nicotinic Receptor in Colonic CD4 T Cells Mediate Dichotomous Response to Nicotine in Murine Models of Th1/Th17- versus Th2-Mediated Colitis
Galitovskiy, V., Qian, J., Chernyavsky, A. I., Marchenko, S. A., Gindi, V., Edwards, R. A., & Grando, S. A. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1002711 · Cited by 110 · see citing works
Role of peripheral corticotropin-releasing factor and urocortin II in intestinal inflammation and motility in terminal ileum
la Fleur, S. E., Wick, E. C., Idumalla, P. S., Grady, E. F., & Bhargava, A. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0408531102 · Cited by 107 · see citing works
Heart rate variability in the irritable bowel syndrome: A review of the literature
Mazurak, N., Seredyuk, N., Sauer, H., Teufel, M., & Enck, P. (2012) · Neurogastroenterology & Motility · doi:10.1111/j.1365-2982.2011.01866.x · Cited by 102 · see citing works
The effect of hypnosis on systemic and rectal mucosal measures of inflammation in ulcerative colitis
Mawdsley, J. E., Jenkins, D. G., Macey, M. G., Langmead, L., & Rampton, D. S. (2008) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2008.01845.x · Cited by 102 · see citing works
Impaired Health-Related Quality of Life in Inflammatory Bowel Diseases Psychosocial Impact and Coping Styles in a National German Sample
Petrak, F., Hardt, J., Clement, T., Börner, N., Egle, U. T., & Hoffmann, S. O. (2001) · Scandinavian Journal of Gastroenterology · doi:10.1080/003655201300051171 · Cited by 101 · see citing works
Immunologically induced neuromodulation of guinea pig nodose ganglion neurons
Undem, B. J., Hubbard, W. C., & Weinreich, D. M. (1993) · Journal of the Autonomic Nervous System · doi:10.1016/0165-1838(93)90376-6 · Cited by 100 · see citing works
Therapeutic effect of urocortin and adrenomedullin in a murine model of Crohn’s disease
González‐Rey, E., Fernandez-Martin, A., Chorny, A., & Delgado, M. (2006) · Gut · doi:10.1136/gut.2005.084525 · Cited by 99 · see citing works
Corticotropin-Releasing Hormone Receptor 2-Deficient Mice Have Reduced Intestinal Inflammatory Responses
Kokkotou, E. G., Torres, D., Moss, A. C., O’Brien, M. J., Grigoriadis, D. E., Karalis, K. P., & Pothoulakis, C. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.5.3355 · Cited by 95 · see citing works
Cortical mapping of visceral pain in patients with GI disorders using functional magnetic resonance imaging
Bernstein, C. N., Frankenstein, U. N., Rawsthorne, P. E., Pitz, M. W., Summers, R., & McIntyre, M. C. (2002) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2002.05464.x · Cited by 93 · see citing works
Self-citation
Brain functional changes in patients with ulcerative colitis
Agostini, A., Filippini, N., Cevolani, D., Agati, R., Leoni, C., Tambasco, R., Calabrese, C., Rizzello, F., Gionchetti, P., Ercolani, M., et al. (2010) · Inflammatory Bowel Diseases · doi:10.1002/ibd.21549 · Cited by 89 · see citing works
Corticotropin-Releasing Factor and the Urocortins Induce the Expression of TLR4 in Macrophages via Activation of the Transcription Factors PU.1 and AP-1
Tsatsanis, C., Androulidaki, A., Alissafi, T., Charalampopoulos, I., Dermitzaki, E., Roger, T., Gravanis, A., & Margioris, A. N. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.176.3.1869 · Cited by 88 · see citing works
Corticotropin releasing factor receptor 1 (CRF1) and CRF2agonists exert an anti‐inflammatory effect during the early phase of inflammation suppressing LPS‐induced TNF‐α release from macrophages via induction of COX‐2 and PGE2
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Corticotropin-releasing hormone antagonists possess anti-inflammatory effects in the mouse ileum
Wlk, M., Wang, C. C., Venihaki, M., Liu, J., Zhao, D., Anton, P. M., Mykoniatis, A., Pan, A., Zacks, J., Karalis, K. P., et al. (2002) · Gastroenterology · doi:10.1053/gast.2002.34783 · Cited by 79 · see citing works
Acute Stress Modulates the Histamine Content of Mast Cells in the Gastrointestinal Tract Through Interleukin‐1 and Corticotropin‐Releasing Factor Release in Rats
Eutamène, H., Théodorou, V., Fioramonti, J., & Bueno, L. P. (2003) · The Journal of Physiology · doi:10.1113/jphysiol.2003.052274 · Cited by 78 · see citing works
Effects of the α7 Nicotinic Acetylcholine Receptor Agonist Gts-21 on the Innate Immune Response in Humans
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Psychological distress and levels of disease activity in inflammatory bowel disease.
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Toll-Like Receptor mRNA Expression Is Selectively Increased in the Colonic Mucosa of Two Animal Models Relevant to Irritable Bowel Syndrome
McKernan, D. P., Nolan, A. M., Brint, E. K., O’Mahony, S. M., Hyland, N. P., Cryan, J. F., & Dinan, T. G. (2009) · PLoS ONE · doi:10.1371/journal.pone.0008226 · Cited by 70 · see citing works
Corticotropin-Releasing Hormone Family of Peptides Regulates Intestinal Angiogenesis
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Altered intestinal microbiota in irritable bowel syndrome: Microbiota in IBS
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Integrated Models of Care in Managing Inflammatory Bowel Disease: A Discussion
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Erratum: Stimulation of the vagus nerve attenuates macrophage activation by activating the Jak2-STAT3 signaling pathway
de Jonge, W. J., van der Zanden, E. P., The, F. O., Bijlsma, M. F., van Westerloo, D. J., Bennink, R. J., Berthoud, H., Uematsu, S., Akira, S., van den Wijngaard, R. M., et al. (2005) · Nature Immunology · doi:10.1038/ni0905-954b · Cited by 68 · see citing works
The Manitoba Inflammatory Bowel Disease Cohort Study: a prospective longitudinal evaluation of the use of complementary and alternative medicine services and products
Rawsthorne, P. E., Clara, I. P., Graff, L. A., Bernstein, K. I., Carr, R., Walker, J. R., Ediger, J. P., Rogala, L., Miller, N., & Bernstein, C. N. (2011) · Gut · doi:10.1136/gutjnl-2011-300219 · Cited by 66 · see citing works
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Stress as a Determinant of Saliva-Mediated Adherence and Coadherence of Oral and Nonoral Microorganisms
Bosch, J. A., Turkenburg, M., Nazmi, K., Veerman, E. C. I., de Geus, E. J. C., & Amerongen, A. V. N. (2003) · Psychosomatic Medicine · doi:10.1097/01.psy.0000074759.71084.ab · Cited by 66 · see citing works
Relationship between disease severity, quality of life and health‐care resource use in a cross‐section of Australian patients with Crohn's disease
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“Bonaz (2013) highlighted that in IBD, chronic stress and HPA dysregulation worsen intestinal inflammation through neuroendocrine-immune interactions.”
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“This is necessary because, for example, depression phenotypes with differing symptom expression have been implicated through work with adolescents with IBD (57), and gut inflammation may impact mental health and therapy response given the role of the brain-gut axis in pathobiology of IBD (58).”
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Authors: Bonaz, B. L., & Bernstein, C. N.
Affiliations: Inserm (FR)
University of Manitoba (CA)
Corresponding author: Bonaz, Bruno L.
ORCID: Bonaz, Bruno L.
Bernstein, Charles N.
Venue: Gastroenterology
Publisher: Elsevier BV
Published: 2013-01
Volume: 144
Issue: 1
Pages: 36-49
ISSN: 0016-5085 (ISSN-L)
DOI: 10.1053/j.gastro.2012.10.003
OpenAlex: W2156744949
Cited by: 667
References: 171
Citations by year: 2026: 38 · 2025: 51 · 2024: 52 · 2023: 44 · 2022: 53 · 2021: 56 · 2020: 55 · 2019: 54 · 2018: 49 · 2017: 51 · 2016: 52 · 2015: 46 · 2014: 45 · 2013: 18 · 2012: 1
FWCI: 4.37
Type: journal article
Language: en
Open access: green
inserm.hal.science
Licence: other-oa
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Gastroenterology (publishedVersion)
PubMed (publishedVersion)
HAL (submittedVersion, other-oa)
Funders: Bristol-Myers Squibb
MSD France
Abbott Canada
Otsuka Pharmaceutical
Janssen Canada
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
Life Sciences › Neuroscience › Neurology › Vagus Nerve Stimulation Research
Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
Keywords: gut-brain axis, inflammatory bowel disease, psychoneuroimmunology, hypothalamic-pituitary-adrenal axis, corticotropin-releasing factor, vagus nerve, cholinergic anti-inflammatory pathway, intestinal barrier, gut microbiota, intestinal immune response, mood disorders, cortisol, heart rate variability, psychotherapy, placebo response, complementary and alternative medicine
MeSH terms: Animals, Anxiety, Autonomic Nervous System, Brain, Corticotropin-Releasing Hormone, Depression, Humans, Hypothalamo-Hypophyseal System, Pituitary-Adrenal System, Stress, Physiological, Stress, Psychological, Inflammatory Bowel Diseases, Gastrointestinal Tract

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Brain–Gut Interactions in Inflammatory Bowel Disease

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