High-resolution manometry evaluation of the role of colonic dysmotility in symptom generation and therapeutic outcomes in functional bowel disorders.

Colonic function is impaired in functional bowel disorders (FBDs), which are characterized by disordered bowel movements (diarrhoea, constipation) and pain, discomfort and bloating. The most important FBDs are functional constipation, chronic diarrhea and the irritable bowel syndrome. We hypothesize that contractions of the colon and their control are disturbed in FBDs, and that this explains their symptoms both in terms of disordered bowel movements and abdominal pain/discomfort/bloating. We will use high resolution manometry, a new tool which uses a sophisticated series pressure-sensitive sensors on a tube, to unravel motor patterns in the different FBDs in comparison to healthy volunteers, and we will study the relationship between symptom occurrence and changes in these motility patterns. We will also take biopsies and will analyse surgical specimens to study changes in the nervous system and the pacemaker cells of the bowel that provide the normal control of bowel motility. In preliminary studies we have seen activation of immune cells in the colon of patients with very severe constipation and this was associated with loss of normal neural function. We will expand these observations and study the correlations to determine whether immune activation is the mechanism that leads to these disturbances.