Abstract
Post-infectious irritable bowel syndrome (PI-IBS) is a common gastrointestinal disorder characterized by persistent abdominal pain despite recovery from acute gastroenteritis. The underlying mechanisms are unclear, although long-term changes in neuronal function, and low grade inflammation of the bowel have been hypothesized. We investigated the presence and mechanism of neuronal sensitization in a unique cohort of individuals who developed PI-IBS following exposure to contaminated drinking water 7 years ago. We provide direct evidence of ongoing sensitization of neuronal signaling in the bowel of patients with PI-IBS. These changes occur in the absence of any detectable tissue inflammation, and instead appear to be driven by pro-nociceptive changes in the gut micro-environment. This is evidenced by the activation of murine colonic afferents, and sensitization responses to capsaicin in dorsal root ganglia (DRGs) following application of supernatants generated from tissue biopsy of patients with PI-IBS. We demonstrate that neuronal signaling within the bowel of PI-IBS patients is sensitized 2 years after the initial infection has resolved. This sensitization appears to be mediated by a persistent pro-nociceptive change in the gut micro-environment, that has the capacity to stimulate visceral afferents and facilitate neuronal TRPV1 signaling.
Highlights
Infectious gastroenteritis (IGE) is a significant risk factor in the development of irritable bowel syndrome (IBS), a chronic functional gastrointestinal disorder, characterized by abdominal pain and altered bowel habit in the absence of ongoing organic pathology
3 individuals who suffered from an infection but did not develop Post-infectious irritable bowel syndrome (PI-IBS) were recruited (PI-healthy volunteers (HVs))
Inflammation enhances pain perception via the activation and/or sensitization of TRP channels, including TRPV114,15, and we hypothesized that the persistence of a low-grade inflammation of the bowel in PI-IBS could lead to long term TRPV1 sensitization
Summary
Infectious gastroenteritis (IGE) is a significant risk factor in the development of irritable bowel syndrome (IBS), a chronic functional gastrointestinal disorder, characterized by abdominal pain and altered bowel habit in the absence of ongoing organic pathology. Mast cell numbers are increased in the terminal ileum of PI-IBS patients following Shigella gastroenteritis[7] Mediators released from these cells such as histamine, IL-1β, IL-6 and TNF-α stimulate or sensitize visceral nociceptors consistent with the hypothesis that nociceptor activation by low grade inflammation underpins abdominal pain in PI-IBS8–10. There is great interest in identifying which specific ion channels are responsible for transducing the depolarization of nociceptors in response to inflammatory mediators Despite this compelling evidence, direct functional data from human studies of sensitized neuroimmune signaling in PI-IBS is lacking. Our data show for the first-time direct evidence of aberrant neuronal signaling in PI-IBS This sensitization of gut function, is not mediated by persistent low grade inflammation, but instead is appears to be mediated by other pro-nociceptive changes in the mucosal micro-environment which modulate TRPV1 signaling
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
