Irritable bowel syndrome and inflammatory bowel disease: infectious gastroenteritis-related disorders?
ABSTRACT Infectious gastroenteritis may be one of the important factors in the development of irritable bowel syndrome (IBS), with
affected individuals often categorized as having post-infectious IBS (PI-IBS), and is linked to the onset of symptoms in approximately
10–20% of patients diagnosed with IBS. Intestinal mucosal infiltration of T cells and mast cells, and enterochromaffin cell
hyperplasia are significant immunological and pathological findings that reveal the pathogenesis of PI-IBS, and results of
laboratory studies using animal models of PI-IBS clearly support clinical evidence. Recently, infectious gastroenteritis has
also been suggested to be associated with the development of inflammatory bowel disease (IBD), and various studies have suggested
that individuals with IBS or IBS-like symptoms may be susceptible to initiation of IBD. However, it is still unclear whether
infectious gastroenteritis is directly or indirectly (through PI-IBS) linked to the initiation of IBD. Additional studies
are necessary to understand the clinical overlap among infectious gastroenteritis, IBS, and IBD.
- [show abstract] [hide abstract]
ABSTRACT: Two proposed hypotheses for irritable bowel syndrome (IBS) are acute gastroenteritis and bacterial overgrowth. We studied whether acute infection with Campylobacter could precipitate bacterial overgrowth in a rat model in order to link the two hypotheses. Sprague-Dawley outbred rats were randomly administered a vehicle or Campylobacter jejuni strain 81-176 by oral gavage. Three months after clearance of the infectious agent, rats had a stool consistency evaluation. After euthanasia, lumenal bacteria counts were measured via quantitative real-time PCR from self-contained segments of the duodenum, jejunum, ileum, cecum and left colon. Adjacent sections of bowel were fixed in formalin for evaluation of intraepithelial lymphocyte counts. Three months after clearance of Campylobacter infection, 57% of Campylobacter infected rats had some alteration in stool consistency compared to 7.4% in mock-infected controls (P < 0.001). Among the rats that received Campylobacter, 27% had evidence of bacterial overgrowth by PCR. These rats also had the highest prevalence of altered stool form and had lower body weight. Consistent with post-infectious IBS in humans, bacterial overgrowth rats demonstrated a significant increase in rectal and left colon intraepithelial lymphocytes. Acute infection with C. jejuni 81-176 precipitates alterations in stool consistency, bacterial overgrowth and rectal lymphocytosis consistent with findings in IBS patients.Digestive Diseases and Sciences 04/2008; 53(4):982-9. · 2.26 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: Mucosal mast cells are implicated in visceral hypersensitivity associated with irritable bowel syndrome (IBS). In this study, we investigated the role of mast cells in the development of visceral hypersensitivity by using mast cell deficient (Ws/Ws) rats and their control (W+/W+). In W+/W+ rats, an injection of 2,4,6-trinitrobenzene sulfonic acid (TNBS) into the proximal colon produced a significant decrease in pain threshold of the distal colon. Severe mucosal necrosis and inflammatory cell infiltration with concomitant increase in tissue myeloperoxidase activity were observed in the proximal colon that was directly insulted by TNBS, whereas neither necrosis nor increased myeloperoxidase activity occurred in the distal colon, indicating that TNBS-induced hypersensitivity is not caused by the local tissue damage or inflammation in the region of the gut where distention stimuli were applied. On the other hand, TNBS failed to elicit visceral hypersensitivity in Ws/Ws rats. This finding indicates that mast cells are essential for development of TNBS-induced visceral hypersensitivity in rats. Since the severity of TNBS-induced proximal colon injury and MPO activity was not affected by mast cell deficiency, it is unlikely that abolishment of visceral hypersensitivity in mast cell deficient rats was a result of altered development of the primary injury in the proximal colon. There was no difference between sham-operated Ws/Ws and W+/W+ rats in colonic pain threshold to distention stimuli, indicating that mast cells play no modulatory roles in normal colonic nociception. The present results support the view that mucosal mast cells play key roles in the pathogenesis of IBS.Life Sciences 03/2008; 82(7-8):419-23. · 2.56 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: Background and aims: Chronic bowel disturbances resembling irritable bowel syndrome (IBS) develop in approximately 25% of patients after an episode of infectious diarrhoea. Although we have previously shown that psychosocial factors operating at the time of, or prior to, the acute illness appear to predict the development of post-infectious IBS (PI-IBS), our finding of an increased inflammatory cell number in the rectum persisting for at least three months after the acute infection suggested that there is also an organic component involved in the development of PI-IBS. To evaluate this further, we measured expressions of interleukin 1beta (IL-1beta) and its receptor antagonist (IL-1ra) in these patients to provide additional evidence that the pathogenesis of PI-IBS is underpinned by an inflammatory process. Sequential rectal biopsy samples were prospectively obtained during and three months after acute gastroenteritis, from eight patients who developed post-infectious IBS (INF-IBS) and seven patients who returned to normal bowel habits after acute gastroenteritis (infection controls, INF-CON). Eighteen healthy volunteers who had not suffered from gastroenteritis in the preceding two years served as normal controls (NOR-CON). IL-1beta and IL-1ra gene expressions were assayed by reverse transcriptase-polymerase chain reaction, and their levels of expression were quantitated by optical densitometry after electrophoresis on agarose gel. INF-IBS patients exhibited significantly greater expression of IL-1beta mRNA in rectal biopsies than INF-CON patients both during and three months after acute gastroenteritis. Moreover, IL-1beta mRNA expression had increased in biopsies taken from INF-IBS patients at three months after the acute infection but no consistent change was observed in INF-CON patients. IL-1beta mRNA expression of INF-IBS patients at three months post gastroenteritis was significantly greater than NOR-CON whereas that of INF-CON patients was not significantly different from NOR-CON. Despite these differential changes in IL-1beta mRNA expression, no significant changes were observed in IL-1ra mRNA expression among the three groups. These findings indicate that those patients who develop IBS post infection exhibit greater IL-1beta mRNA expression, both during and after the infection, compared with individuals who do not develop PI-IBS. We conclude that such patients may be susceptible to inflammatory stimuli, and that inflammation may play a role in the pathogenesis of PI-IBS.Gut 05/2003; 52(4):523-6. · 10.73 Impact Factor