Manipulation of Visceral Sensitivity and Immune System in IBS
Status:
Unknown status
Trial end date:
1969-12-31
Target enrollment:
Participant gender:
Summary
Irritable bowel syndrome (IBS) is a common condition. At least 20% of the population suffer
from IBS. The symptoms of abdominal pain, diarrhoea, constipation, bloating and difficulty
with bowel motions are often disabling. Many of those affected are young and report a poor
quality of life (QOL) to a degree that is similar to gut inflammatory conditions like
ulcerative colitis and Crohn's disease. Yet the impact of IBS on patients' lives is often
underestimated. This is probably because unlike inflammatory bowel disease, in which the
bowel is inflammed and bleeds, the bowel in IBS looks normal. Instead the problem is of
abnormal functioning of the gut the cause of which is unknown.
Currently therapy for IBS is limited and until recently therapy has focused on treating the
symptoms to improve QOL primarily because the underlying mechanism of IBS is poorly
understood. However as more processes are being implicated in IBS e.g. visceral
hypersensitivity (excessive response to sensory stimuli within the gut), infection, immune
activation, dysmotility and abnormal gut fermentation , the potential for new therapies looks
promising. The evidence that gut bacteria play a role in inducing IBS symptoms is due to
observations of an improvement of IBS symptoms with probiotic therapy (bacterial supplements)
and antibiotic therapy.
Patients with IBS are hypersensitive to colorectal distension compared with healthy controls.
Studies carried out in our unit have shown that visceral pain thresholds in response to
stress are lower in patients with IBS compared with healthy volunteers. This hypersensitivity
is apparent in response to both a physical and chemical stimulus but the triggers to visceral
hypersensitivity remain largely unknown. Animal models suggest roles for both host immune
response and intestinal bacteria in the induction of visceral hypersensitivity. This proposal
will focus on further exploration of the mechanisms underlying visceral hypersensitivity to
direct future targeting of therapy.
Previous independent studies showed that (a) bacteria reduce visceral hypersensitivity,
(b)probiotic therapy can alter gut immune response and (c) gut sensation is affected by the
type of immune cells in the gut. Our research proposal will investigate the relationship
between gut bacteria, the immune system and the sensory gut nerves in order to understand how
IBS symptoms are generated. This understanding will be the critical for effective future drug
treatment.