The relation between stress, microscopic inflammation and visceral
sensitivity in patients with irritable bowel syndrome.
B. Braak,1, *, T. K. Klooker1, *, M. M. Wouters2, O. Welting3, C. M. van der Loos4, O. I.
Stanisor3, S. van Diest 3, R. M. van den Wijngaard3 and G. E. E. Boeckxstaens1,2,5.
1
Department of Gastroenterology and Hepatology, AMC, Amsterdam, the Netherlands; 2Translational
Research Center for Gastrointestinal Disorders, University Hospital Leuven, Catholic University
Leuven, Leuven, Belgium; 3Tytgat Institute of Liver and Intestinal Research, AMC, Amsterdam, the
Netherlands; 4Department of Pathology, AMC, Amsterdam, the Netherlands, 5Department of
Gastroenterology, University Hospital Leuven, Catholic University Leuven, Leuven, Belgium. *Both
authors participated equally and sharing first authorship.
ABSTRACT
Repeated exposure to stress leads to mast cell degranulation, microscopic
inflammation and subsequent visceral hypersensitivity in animal models. To what
extent this pathophysiological pathway plays a role in patients with the irritable bowel
syndrome (IBS) has not been properly investigated. The aim of this study was to
assess the relationship between visceral hypersensitivity, microscopic inflammation
and the stress response in IBS.
Microscopic inflammation of the descending colonic mucosa was evaluated by
immunohistochemistry in IBS patients and healthy volunteers (HV). Rectal sensitivity
was assessed by a barostat study using an intermittent pressure-controlled
distension protocol. Salivary cortisol to a series of 3 psychological stress tests (i.e.
stroop test (color-word conflicting test), mirror tracing test and public speech test)
was measured to assess the stress response in a subgroup of patients. peak
cortisol levels, expressed as the maximal increase from baseline, was calculated
(median (range), ug/ml).
66 IBS patients (74% female (F), age 38 ± 2 yr) and 20 HV (65% F, 31 ± 3 yr) were
included in this study. Of all IBS patients, 52% (n=33) were considered visceral
hypersensitive to rectal distension (i.e. threshold of discomfort <24 mm Hg above
MDP). In IBS, mast cells (IBS: 186 ± 10 vs. HV: 370 ± 39 / mm2, p<0.001) CD8 Tcells (IBS: 388 ± 28 vs. HV: 526 ± 50/ mm2, p=0.02) and macrophages (IBS: 729 ± 64
vs. HV: 1261 ± 146/ mm2, p<0.003) were decreased . Similarly,  free light chain
(FLC) positive mast cells were decreased (IBS: 1 (0-34) vs. HV: 7 (0-33) /mm2,
p=0.004), but not IgE- and IgG positive mast cells. There were no differences
between hypersensitive and normosensitive IBS patients. No relation was found
between any of the immune cells studied and the thresholds of discomfort, urge or
IBS symptoms. 22 IBS and 18 HV underwent the stress test. Baseline and peak
cortisol were comparable between IBS and HV (IBS: baseline 5.3 (22.1), peak 1.3
(18.3); HV: baseline 6.8 (19.7), peak 1.3 (29.6); NS). The HPA-axis response to
stress was not correlated with the number of mast cells (IBS: r=0.41, p=0.1; HV: r=0.26, p=0.3) or the presence of visceral hypersensitivity.
CONCLUSIONS: Our data show a reduction of the number of mast cells, macrophages,
T-cells and FLC positive mast cells in IBS compared to HV. There is no association
between the number of these immune cells and the presence of visceral
hypersensitivity or abnormal stress response. Our data question the role of
microscopic inflammation as underlying mechanism of visceral hypersensitivity, but
rather suggest dysregulation of the mucosal immune system in IBS.