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The Immune System in Irritable Bowel Syndrome
Open accessAbstract
The potential relevance of systemic and gastrointestinal immune activation in the pathophysiology and symptom generation in the irritable bowel syndrome (IBS) is supported by a number of observations. Infectious gastroenteritis is the strongest risk factor for the development of IBS and increased rates of IBS-like symptoms have been detected in patients with inflammatory bowel disease in remission or in celiac disease patients on a gluten free diet. The number of T cells and mast cells in the small and large intestine of patients with IBS is increased in a large proportion of patients with IBS over healthy controls. Mediators released by immune cells and likely from other non-immune competent cells impact on the function of enteric and sensory afferent nerves as well as on epithelial tight junctions controlling mucosal barrier of recipient animals, isolated human gut tissues or cell culture systems. Antibodies against microbiota antigens (bacterial flagellin), and increased levels of cytokines have been detected systemically in the peripheral blood advocating the existence of abnormal host-microbial interactions and systemic immune responses. Nonetheless, there is wide overlap of data obtained in healthy controls; in addition, the subsets of patients showing immune activation have yet to be clearly identified. Gender, age, geographic differences, genetic predisposition, diet and differences in the intestinal microbiota likely play a role and further research has to be done to clarify their relevance as potential mechanisms in the described immune system dysregulation. Immune activation has stimulated interest for the potential identification of biomarkers useful for clinical and research purposes and the development of novel therapeutic approaches.
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“These mediators may alter nociceptive pathways in IBS115 or increase intestinal permeability116.”
From The gut Microbiome in adult and pediatric functional gastrointestinal disorders (2019) · cites this paper as [116]
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Cites
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Self-citationReview article: probiotics and prebiotics in irritable bowel syndrome
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T-Cell Activation in Patients With Irritable Bowel Syndrome
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Role of corticotropin-releasing hormone in irritable bowel syndrome and intestinal inflammation
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“tential therapeutic target in these patients which deserve further attention.(67) The contribution of genetic polymorphysms to immune acti-”
Dinan, T. G., Clarke, G., Quigley, E. M. M., Scott, L. V., Shanahan, F., Cryan, J., Cooney, J., & Keeling, P. W. N. (2008) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2008.01871.x · Cited by 136
Roka, R., Rosztóczy, A., Lévêque, M., Izbéki, F., Nagy, F., Molnár, T., Lonovics, J., Garcia-Villar, R., Fioramonti, J., Wittmann, T., et al. (2007) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2006.12.004 · Cited by 136
CORINALDESI, R., STANGHELLINI, V., CREMON, C., GARGANO, L., COGLIANDRO, R. F., DE GIORGIO, R., BARTESAGHI, G., CANOVI, B., & BARBARA, G. (2009) · Alimentary Pharmacology & Therapeutics · doi:10.1111/j.1365-2036.2009.04041.x · Cited by 131 · cited 1×
“nosalicylic acid (mesalazine, 800 mg 3 times daily for 8 weeks) on intestinal immune cells and symptom perception in patients with IBS.(87) Compared with placebo, mesalazine significantly reduced”
Self-citationAlterations in mucosal immunity identified in the colon of patients with irritable bowel syndrome
Aerssens, J., Camilleri, M., Talloen, W., Thielemans, L., Göhlmann, H. W. H., Van den Wyngaert, I., Thielemans, T., De Hoogt, R., Andrews, C. N., Bharucha, A. E., et al. (2008) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2007.11.012 · Cited by 124 · cited 1×
“teration of gene expression of several components of the host mucosal immune response to microbial pathogens.(43) Most studies reported increased infiltration of immune cells in the rectum(24) and colon,(33) however, increased mast cell numbers(44,45) and intraepithelial lymphocytes(46) have also been detected in the…”
Antibodies to flagellin indicate reactivity to bacterial antigens in IBS patients
Schoepfer, A. M., Schaffer, T., Seibold‐schmid, B., Müller, S., & Seibold, F. (2008) · Neurogastroenterology & Motility · doi:10.1111/j.1365-2982.2008.01166.x · Cited by 120 · cited 1×
“An increased IgG+ B cell frequency has been reported in the blood of IBS patients,(35) which is in keeping with the detection of circulating antibodies to bacterial flagellin in IBS.(36) However, 2 studies reported that the numbers of mucosal B cells were unchanged in IBS patients vs controls.”
Midhagen, G., & Hallert, C. (2003) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2003.07632.x · Cited by 109 · cited 1×
“IBS-like symptoms has been reported in patients with celiac disease living on a gluten free diet and after apparent resolution of mucosal damage and immune activation.(25,26) Whether a mild im-”
Symptom overlap and comorbidity of irritable bowel syndrome with other conditions
Frissora, C. L., & Koch, K. L. (2005) · Current Gastroenterology Reports · doi:10.1007/s11894-005-0018-9 · Cited by 100 · cited 1×
“(eg, functional dyspepsia) and extra-intestinal (eg, migraine, fibromyalgia and interstitial cystitis) disorders.(27) Interestingly, mild infiltration of immune cells interacting with tissue in-”
Öhman, L., Isaksson, S., Lundgren, A., Simrén, M., & Sjövall, H. (2005) · Clinical Gastroenterology and Hepatology · doi:10.1016/s1542-3565(05)00410-6 · Cited by 98 · cited 1×
“In particular, a high proportion of patients displays an increased frequency of circulating cytotoxic CD8+ T cells expressing the gut homing integrin α4β7.(31) This well correlates with increased CD8+ T cells in the lamina propria and epithelium (intraepithelial lymphocytes) in patients with nonspecific and post-infec…”
Rather, L. J. (1971) · PubMed · Cited by 97
Porras, M., Martín, M. T., Yang, P., Jury, J., Perdue, M. H., & Vergara, P. (2006) · Inflammatory Bowel Diseases · doi:10.1097/01.mib.0000231571.88806.62 · Cited by 76 · cited 1×
“On the other hand, increased permeability could participate to ongoing intestinal immune stimulation by uncontrolled exposure of the lamina propria to an abnormal antigenic load.(70) Several lines of evidence suggest the contribution of intestinal microbiota in the pathophysiology of IBS including: (1) presence”
LUNARDI, C., BAMBARA, L. M., BIASI, D., CORTINA, P., PEROLI, P., NICOLIS, F., FAVARI, F., & PACOR, M. L. (1991) · Clinical & Experimental Allergy · doi:10.1111/j.1365-2222.1991.tb00848.x · Cited by 72
Human mast cell mediator cocktail excites neurons in human and guinea‐pig enteric nervous system
Schemann, M., Michel, K., CEREGRZYN, M., Zeller, F., Seidl, S., & Bischoff, S. C. (2004) · Neurogastroenterology & Motility · doi:10.1111/j.1365-2982.2004.00591.x · Cited by 72 · cited 1×
“2).(5,6,8,57) Mucosal mediators of IBS patients, but not controls, evoked increased activation of sensory pain”
Elsenbruch, S., Holtmann, G., Oezcan, D., Lysson, A., Janssen, O. E., Goebel, M. U., & Schedlowski, M. (2004) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2004.04138.x · Cited by 68
Enestrbm, S., Bengtsson, A., & Frddin, T. (1997) · Scandinavian Journal of Rheumatology · doi:10.3109/03009749709105321 · Cited by 62
CD4+CD25+ regulatory T cells in irritable bowel syndrome patients
Holmén, N., Isaksson, S., Simrén, M., Sjövall, H., & Öhman, L. (2006) · Neurogastroenterology & Motility · doi:10.1111/j.1365-2982.2006.00878.x · Cited by 38 · cited 1×
“suppressing inflammation, showed similar frequencies in IBS patients and controls.(34) The role of B cells and relative antibody production is controversial.”
Biomarkers in IBS: when will they replace symptoms for diagnosis and management?: Table 1
Barbara, G., & Stanghellini, V. (2009) · Gut · doi:10.1136/gut.2008.169672 · Cited by 37 · cited 2×
“markers so far described show wide overlap with controls and increased levels of pro-inflammatory cytokines have been detected also in patients with other functional GI disorders(42) or depression,(82) suggesting poor sensitivity and specificity.(80) On the other hand more invasive studies (eg, mast cells in proximity…”
Self-citationA pilot study of colonic B cell pattern in irritable bowel syndrome
Forshammar, J., Isaksson, S., Strid, H., Stotzer, P.-O., Sjövall, H., Simrén, M., & Öhman, L. (2008) · Scandinavian Journal of Gastroenterology · doi:10.1080/00365520802272126 · Cited by 33
Use of oral sodium cromoglycate in persistent diarrhoea.
Bolin, T. D. (1980) · Gut · doi:10.1136/gut.21.10.848 · Cited by 32 · cited 1×
“356 Journal of Neurogastroenterology and Motility IBS dates back to the ‘80s when a significant 40% symptomatic improvement over control was shown in a small cohort of IBS patients.(84) Other studies have provided evidence of improvement of abdominal pain and diarrhea in IBS over placebo(85) or elimination diet.”
Bafutto, M., de Almeida, J. R. D., Leite, N. V., Oliveira, Ê., Gabriel-Neto, S., & Rezende-filho, J. (2011) · Arquivos de Gastroenterologia · doi:10.1590/s0004-28032011000100008 · Cited by 28
Aminosalicylates and Other Anti-Inflammatory Compounds for Irritable Bowel Syndrome
Barbara, G., Stanghellini, V., Cremon, C., GIORGIO, R. D., Fronzoni, L., Serra, M., & Corinaldesi, R. (2009) · Digestive Diseases · doi:10.1159/000268131 · Cited by 27
Self-citationProbiotics and Irritable Bowel Syndrome
Barbara, G., Stanghellini, V., Cremon, C., GIORGIO, R. D., Gargano, L., Cogliandro, R. F., Pallotti, F., & Corinaldesi, R. (2008) · Journal of Clinical Gastroenterology · doi:10.1097/mcg.0b013e31817da129 · Cited by 24 · cited 1×
“The intestinal microbiota has been the target of different approaches including prebiotics, probiotics, synbiotics, non-absorbable and systemic antibiotics.(62) A number of mechanisms of action make probiotics very attractive for the treatment of IBS.”
Self-citationAndrews, C. N., Petcu, R., Griffiths, T. A. M., Bjarnason, J., Chapman, K., Cellars, L., Vergnolle, N., & Rioux, K. P. (2008) · Gastroenterology · doi:10.1016/s0016-5085(08)62558-5 · Cited by 8
Bafutto, M., de Almeida, J. R., Almeida, R. C., Almeida, T. C., Leite, N. V., & Filho, J. R. (2008) · Gastroenterology · doi:10.1016/s0016-5085(08)63136-4 · Cited by 7
Bafutto, M., de Almeida, J. R., Leite, N. V., & Filho, J. R. (2008) · Gastroenterology · doi:10.1016/s0016-5085(08)62463-4 · Cited by 5
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Cited by
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Intestinal permeability – a new target for disease prevention and therapy
Bischoff, S. C., Barbara, G., Buurman, W., Ockhuizen, T., Schulzke, J.-D., Serino, M., Tilg, H., Watson, A., & Wells, J. M. (2014) · BMC Gastroenterology · doi:10.1186/s12876-014-0189-7 · Cited by 1,755
“Interestingly, several studies have provided evidence of low-grade immune activation and release of inflammatory molecules in IBS which in turn maintain the increase in intestinal permeability [195].”
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Self-citationIntestinal microbiota in functional bowel disorders: a Rome foundation report
Simrén, M., Barbara, G., Flint, H. J., Spiegel, B. M. R., Spiller, R. C., Vanner, S., Verdu, E. F., Whorwell, P. J., & Zoetendal, E. G. (2013) · Gut · doi:10.1136/gutjnl-2012-302167 · Cited by 939
Self-citationFODMAPs alter symptoms and the metabolome of patients with IBS: a randomised controlled trial
McIntosh, K., Reed, D. E., Schneider, T., Dang, F., Keshteli, A. H., Palma, G. D., Madsen, K. L., Berčík, P., & Vanner, S. J. (2016) · Gut · doi:10.1136/gutjnl-2015-311339 · Cited by 495
Techniques used to characterize the gut microbiota: a guide for the clinician
Fraher, M. H., O'Toole, P. W., & Quigley, E. M. M. (2012) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2012.44 · Cited by 385
Metadata
- Authors
- Barbara, G., Cremon, C., Carini, G., Bellacosa, L., Zecchi, L., Giorgio, R. D., Corinaldesi, R., & Stanghellini, V.
- Affiliations
- University of Bologna (IT)
- Corresponding author
- Barbara, Giovanni
- Venue
- Journal of Neurogastroenterology and Motility
- Published
- 2011-10-31
- Volume
- 17
- Issue
- 4
- Pages
- 349-359
- ISSN
- 2093-0879 (ISSN-L)
- 2093-0887
- PMC
- PMC3228974
- OpenAlex
- W2154410960
- Cited by
- 211
- References
- 91
- Citations by year
- 2026: 8 · 2025: 10 · 2024: 9 · 2023: 10 · 2022: 15 · 2021: 10 · 2020: 21 · 2019: 13 · 2018: 20 · 2017: 15 · 2016: 20 · 2015: 12 · 2014: 18 · 2013: 17 · 2012: 12
- FWCI
- 15.76
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Journal of Neurogastroenterology and Motility (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion)
- Institutional Research Information System University of Ferrara (University of Ferrara) (submittedVersion)
- Topics
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Gastroenterology › Inflammatory Bowel Disease
- Keywords
- irritable bowel syndrome, immune activation, gut microbiota, T cells, mast cells, enteric nerves, tight junctions, mucosal barrier, host-microbe interactions, inflammatory bowel disease, celiac disease, gluten-free diet, infectious gastroenteritis, cytokines, biomarkers, immune dysregulation
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