Mucosal Immune Activation in Irritable Bowel Syndrome: Gender-Dependence and Association With Digestive Symptoms
Abstract
OBJECTIVES: Immune activation may be involved in the pathogenesis of irritable bowel syndrome (IBS). However, the relative magnitude of this immune component and its correlation with gender and gastrointestinal complaints in IBS patients remains poorly elucidated. METHODS: We enrolled 48 IBS patients, with either diarrhea or constipation, 12 patients with microscopic colitis, 20 patients with ulcerative colitis, and 24 healthy controls. Colonic immunocytes were identified with quantitative immunohistochemistry on mucosal biopsies. Gastrointestinal symptoms were assessed using a validated questionnaire. RESULTS: IBS patients showed a significant 72% increase in mucosal immune cells compared to controls (P<0.001). Further analyses showed that increased immune cells were present in 50% of the IBS patients. The magnitude of the immune infiltrate in IBS was significantly lower than that of microscopic colitis or ulcerative colitis (42% and 124% increases vs. IBS, respectively; P<0.001). Compared with controls, IBS patients had increased numbers of CD3+, CD4+, and CD8+ T cells and mast cells (P<0.001). Compared to male IBS patients, female IBS patients had greater numbers of mast cells (P=0.066), but lower numbers of CD3+ and CD8+ T cells (P=0.002 and <0.001, respectively). Mucosal mast cell infiltration of IBS patients was significantly associated with abdominal bloating frequency (P=0.022) and with symptoms of dysmotility-like dyspepsia (P=0.001), but not ulcer-like dyspepsia. CONCLUSIONS: A large subset of IBS patients shows gender-dependent mucosal infiltration of immunocytes that correlates with abdominal bloating and dysmotility-like dyspepsia. These results provide the rationale for considering immune mechanisms as a pathophysiological component in a subset of IBS patients.
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Patients with IBS have increased concentrations of inflammatory/immune cells in intestinal tissue compared with controls.
“Evidence supporting this hypothesis includes increased concentrations of inflammatory/immune cells in intestinal tissue from IBS patients, altered levels of pro- and anti-inflammatory cytokines in the GI tract and peripheral blood of patients with IBS (Table 1) (11, 13, 24, 36, 46, 50, 51, 62, 73, 75, 89, 90, 94, 98, 102, 118, 121–124, 168, 174, 185, 187), and IBS-associated polymorphisms in genes”
From Intestinal microbiota and immune function in the pathogenesis of irritable bowel syndrome (2013) · cites this paper as [46]
Increased concentrations of CD3+ T cells in the colon and rectum and in the myenteric plexus of the small intestine were increased in patients with IBS or PI-IBS compared with normal controls.
“Additionally, increased concentrations of CD3+ T cells in the colon and rectum and in the myenteric plexus of the small intestine were increased in these patients compared with normal controls (36, 46, 57, 58, 89, 94, 133, 168, 174).”
From Intestinal microbiota and immune function in the pathogenesis of irritable bowel syndrome (2013) · cites this paper as [46]
Several studies have demonstrated increased concentrations of activated mast cells in patients with IBS compared with controls.
“Several studies have demonstrated increased concentrations of activated mast cells in patients with IBS compared with controls (11, 13, 24, 46, 89, 94, 121, 187).”
From Intestinal microbiota and immune function in the pathogenesis of irritable bowel syndrome (2013) · cites this paper as [46]
The abundance of mast cells in patients with IBS may correlate with some symptoms of IBS, including bloating and abdominal pain.
“The abundance of mast cells in patients with IBS may correlate with some symptoms of IBS, including bloating and abdominal pain (2, 46).”
From Intestinal microbiota and immune function in the pathogenesis of irritable bowel syndrome (2013) · cites this paper as [46]
Concentrations of cytotoxic CD8+ T cells may be elevated in the lamina propria of the colon of patients with IBS or PI-IBS, although this finding was disputed by others.
“Concentrations of cytotoxic CD8+ T cells, which comprise most of the intraepithelial T cell population (126) may also be elevated in the lamina propria of the colon of patients with IBS (46, 123) or PI-IBS (89) although this finding was disputed by others (36).”
From Intestinal microbiota and immune function in the pathogenesis of irritable bowel syndrome (2013) · cites this paper as [46]
Patients with IBS have altered levels of pro- and anti-inflammatory cytokines in the GI tract and peripheral blood compared with controls.
“Evidence supporting this hypothesis includes increased concentrations of inflammatory/immune cells in intestinal tissue from IBS patients, altered levels of pro- and anti-inflammatory cytokines in the GI tract and peripheral blood of patients with IBS (Table 1) (11, 13, 24, 36, 46, 50, 51, 62, 73, 75, 89, 90, 94, 98, 102, 118, 121–124, 168, 174, 185, 187), and IBS-associated polymorphisms in genes”
From Intestinal microbiota and immune function in the pathogenesis of irritable bowel syndrome (2013) · cites this paper as [46]
Increased levels of CD4+ T helper cells were observed in the colon of patients with IBS in one study but not in another.
“Similarly, increased levels of CD4+ T helper cells were observed in the colon of patients with IBS in one study (46) but not in another (123), leaving the role for this T cell subtype in IBS unclear.”
From Intestinal microbiota and immune function in the pathogenesis of irritable bowel syndrome (2013) · cites this paper as [46]
No differences in total B cell numbers were observed in the colons of IBS patients.
“Although no differences in total B cell numbers were observed in the colons of IBS patients (46), a single study reported reduced levels of IgA+ B cells in the ascending but not sigmoid colon compared with controls, whereas levels of IgG+, IgM+, and IgE+ B cells in both the ascending and sigmoid colon were normal (62).”
From Intestinal microbiota and immune function in the pathogenesis of irritable bowel syndrome (2013) · cites this paper as [46]
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References 45 · Cited by 342
- Authors
- Cremon, C., Gargano, L., Morselli-Labate, A. M., Santini, D., Cogliandro, R. F., De Giorgio, R., Stanghellini, V., Corinaldesi, R., & Barbara, G.
- Affiliations
- IRCCS Azienda Ospedliero-Universitaria di Bologna Policlinico di Sant'Orsola (IT)
- University of Bologna (IT)
- Corresponding author
- Barbara, Giovanni
- ORCID
- Venue
- The American Journal of Gastroenterology
- Published
- 2009-01-13
- Volume
- 104
- Issue
- 2
- Pages
- 392-400
- ISSN
- 0002-9270 (ISSN-L)
- 1572-0241
- OpenAlex
- W1972565216
- Cited by
- 342
- References
- 45
- Citations by year
- 2026: 2 · 2025: 10 · 2024: 15 · 2023: 3 · 2022: 15 · 2021: 19 · 2020: 15 · 2019: 15 · 2018: 18 · 2017: 19 · 2016: 31 · 2015: 28 · 2014: 32 · 2013: 28 · 2012: 28
- FWCI
- 31.54
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The American Journal of Gastroenterology (publishedVersion)
- 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 › Epidemiology › Microscopic Colitis
- Keywords
- irritable bowel syndrome, mucosal immune activation, gender differences, mast cells, T cells, colonic mucosa, bloating, dyspepsia, dysmotility, microscopic colitis, ulcerative colitis, immune cell infiltration
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Colitis, Ulcerative, Constipation, Diarrhea, Female, Humans, Immunity, Cellular, Intestinal Mucosa, Male, Middle Aged, Sex Factors, Case-Control Studies, Immunity, Mucosal, Irritable Bowel Syndrome, Colitis, Microscopic, Young Adult
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