Bacillary dysentery as a causative factor of irritable bowel syndrome and its pathogenesis

Abstract

Background and aims: The incidence of irritable bowel syndrome (IBS) or functional bowel disorders (FBD) after bacillary dysentery (BD) has not been extensively evaluated, and little is known of the pathogenesis of post-infective (PI) IBS. Therefore, we investigated the incidence of IBS and FBD in a Chinese patient population who had recovered from BD. To further elucidate its pathogenesis, neuroimmunological changes, including interleukins (IL), mast cells, neuropeptides, and the relationship between mast cells and intestinal nerves, were investigated.

Methods: A cohort study of 295 patients who had recovered from BD (shigella identified from stool in 71.4%) and 243 control subjects consisting of patient siblings or spouses who had not been infected with BD were included in the study. All subjects were followed up using questionnaires for 1-2 years to explore the incidence of FBD and IBS, as defined by the Rome II criteria. In 56 cases of IBS (PI and non-PI) from another source, the number of mast cells in biopsy specimens from the intestinal mucosa were stained with antitryptase antibody and counted under light microscopy. Also, the relationship of mast cells to neurone specific enolase (NSE), substance P (SP), 5-hydroxytryptamine (5-HT), or calcitonin gene related peptide positive nerve fibres was observed using double staining with alcian blue and neuropeptide antibodies. In 30 cases of IBS (PI-IBS, n = 15) taken at random from the 56 cases, expression of interleukin (IL)-1alpha, IL-1beta, and IL-1 receptor antagonist (IL-1ra) mRNAs in intestinal mucosa were identified using reverse transcription-polymerase chain reaction. The above results were compared with 12 non-IBS controls.

Results: In the BD infected cohort, the incidences of FBD and IBS were 22.4% and 8.1% (in total)-10.2% (among those in who shigella were identified) respectively, which were significantly higher (p<0.01) than the incidences of FBD (7.4%) and IBS (0.8%) in the control cohort. A longer duration of diarrhoea (>or=7 days) was associated with a higher risk of developing FBD (odds ratio 3.49 (95% confidence interval 1.71-7.13)). Expression of IL-1beta mRNA in terminal ileum and rectosigmoid mucosa was significantly higher in PI-IBS patients (p<0.01). The number of mast cells in the terminal ileum mucosa in PI-IBS (11.19 (2.83)) and non-PI-IBS patients (10.78 (1.23)) was significantly increased compared with that (6.05 (0.51)) in control subjects (p<0.01). Also, in the terminal ileum and rectosigmoid mucosa of IBS patients, the density of NSE, SP, and 5-HT positively stained nerve fibres increased (p<0.05) and appeared in clusters, surrounding an increased number of mast cells (p<0.01 compared with controls).

Conclusions: BD is a causative factor in PI-IBS. The immune and nervous system may both play important roles in the pathogenesis of PI-IBS.

Figure 1

Flow chart indicating the number of patients and their sources. BD, bacillary dysentery; FBD, functional bowel disorder; IBS, irritable bowel syndrome; PI, post-infective.

Figure 2

Interleukin 1β (IL-1β) mRNA expression in the intestinal mucosa of irritable bowel syndrome (IBS) patients and controls. Electrophoresis of reverse transcription-polymerase chain reaction products; IL-1β mRNAs are expressed as their complementary cDNAs identified at 436 bp. Mucosal specimens were from: lane 1, rectosigmoid junction of a post-infective (PI)-IBS patient; lane 2, terminal ileum of a PI-IBS patient; lane 3, rectosigmoid junction of a non-PI-IBS patient; lane 4, terminal ileum of a non-PI-IBS patient; lane 5, rectosigmoid junction of a control subject; and lane 6, terminal ileum of a control subject. Expression of IL-1β mRNAs in PI-IBS patients (as represented in lanes 1 and 2) was significantly higher that that in non-PI-IBS patients and controls.

Figure 3

Expression of neurone specific enolase (NSE) stained nerve fibres around mast cells in the mucosa (×1000) of the terminal ileum in an irritable bowel syndrome (IBS) patient (A) and a control subject (B). Mast cells stained blue and NSE containing fibres stained red. There is a high density of dark red NSE fibres appearing in clusters around multiple mast cells in the mucosa of the IBS patient compared with very limited staining fibres around the few mast cells in the control subject.