Fundamentals of neurogastroenterology: Basic science

This review examines the fundamentals of neurogastroenterology that may underlie the pathophysiology of functional GI disorders (FGIDs). It was prepared by an invited committee of international experts and represents an abbreviated version of their consensus document that will be published in its entirety in the forthcoming book and online version entitled Rome IV. It emphasizes recent advances in our understanding of the enteric nervous system, sensory physiology underlying pain, and stress signaling pathways. There is also a focus on neuroimmmune signaling and intestinal barrier function, given the recent evidence implicating the microbiome, diet, and mucosal immune activation in FGIDs. Together, these advances provide a host of exciting new targets to identify and treat FGIDs, and new areas for future research into their pathophysiology

Serotonin and GI Disorders: An Update on Clinical and Experimental Studies

The gastrointestinal (GI) tract is the largest producer of serotonin (5-hydroxytryptamine (5-HT)) in the body, and as such it is intimately connected with GI function and physiology. 5-HT produced by enterochromaffin (EC) cells is an important enteric mucosal signaling molecule and has been implicated in a number of GI diseases, including inflammatory bowel disease and functional disorders such as irritable bowel syndrome. This review will focus on what is known of basic 5-HT physiology and also on the emerging evidence for its novel role in activation of immune response and inflammation in the gut. Utilizing pubmed.gov, search terms such as “5-HT,” “EC cell,” and “colitis,” as well as pertinent reviews, were used to develop a brief overview of EC cell biology and the association between 5-HT and various GI disorders. It is the aim of this review to provide the readers with an update on EC cell biology and current understanding on the role of 5-HT in GI disorders specifically in inflammatory conditions

The TNF-α antagonist etanerceptreverses age-related decreases in colonic SERT expression and faecal output in mice

Treatment for chronic constipation in older people is challenging and the condition has a major impact on quality of life. A lack of understanding about the causes of this condition has hampered the development of effective treatments. 5-HT is an important pro-kinetic agent in the colon. We examined whether alterations in colonic 5-HT signalling underlie age–related changes in faecal output in mice and whether these changes were due to an increase in TNF-α. Components of the 5-HT signalling system (5-HT, 5-HIAA, SERT) and TNF-α expression were examined in the distal colon of 3, 12, 18 and 24- month old mice and faecal output and water content monitored under control conditions and following the administration of etanercept (TNF-α inhibitor; 1 mg Kg-1). Faecal output and water content were reduced in aged animals. Age increased mucosal 5-HT availability and TNF-α expression and decreased mucosal SERT expression and 5-HIAA. Etanercept treatment of old mice reversed these changes, suggesting that age-related changes in TNFα expression are an important regulator of mucosal 5-HT signalling and pellet output and water content in old mice. These data point to “anti-TNFα” drugs as potential treatments for age-related chronic constipation

Alterations in melatonin and 5‐HT signalling in the colonic mucosa of mice with dextran‐sodium sulfate‐induced colitis

Inflammatory bowel disease (IBD) is characterized by pain, bleeding, cramping and altered gastrointestinal (GI) function. Changes in mucosal 5‐HT (serotonin) signalling occur in animal models of colitis and in humans suffering from IBD. Melatonin is co‐released with 5‐HT from the mucosa and has a wide variety of actions in the GI tract. Here, we examined how melatonin signalling is affected by colitis and determined how this relates to 5‐HT signalling. Experimental Approach Using electroanalytical approaches, we investigated how 5‐HT release, reuptake and availability as well as melatonin availability are altered in dextran sodium sulfate (DSS)‐induced colitis in mice. Studies were conducted to explore if melatonin treatment during active colitis could reduce the severity of colitis. Key Results We observed an increase in 5‐HT and a decrease in melatonin availability in DSS‐induced colitis. A significant reduction in 5‐HT reuptake was observed in DSS‐induced colitis animals. A reduction in the content of 5‐HT was observed, but no difference in tryptophan levels were observed. A reduction in deoxycholic acid‐stimulated 5‐HT availability and a significant reduction in mechanically‐stimulated 5‐HT and melatonin availability were observed in DSS‐induced colitis. Orally or rectally administered melatonin once colitis was established did not significantly suppress inflammation. Conclusion and Implications Our data suggest that DSS‐induced colitis results in a reduction in melatonin availability and an increase in 5‐HT availability, due to a reduction/loss of tryptophan hydroxylase 1 enzyme, 5‐HT content and 5‐HT transporters. Mechanosensory release was more susceptible to inflammation when compared with chemosensory release

What are the consequences of enlarging the extraction site to exteriorize a large specimen during laparoscopic surgery for Crohn's enteritis?

Aim: The implications of extraction site enlargement for the removal of large specimens during laparoscopic surgery for Crohn's disease have not been clearly described; such a description is the aim of this study. Method: An institutional database was queried to identify patients undergoing laparoscopic resection for Crohn's disease through midline incision between 1995 and 2013. Perioperative outcomes were compared among cases completed through their initial extraction site (L), completed after increasing the length of the initial extraction site (IL) for specimen exteriorization, and cases converted to open surgery (C). Univariate and multivariate statistical analyses were performed. Results: Out of 309 patients, 52 required IL and 36 required C. Heavier, older, male patients were more likely to require IL or C. There were no differences in disease behaviour (P = 0.260), procedures performed (P = 0.12) or postoperative morbidity (P = 0.33). IL and L groups had a comparable initial length of hospital stay (LOS), which was shorter than in the C group. While there were no significant differences in causes of readmission (P = 0.31), IL had increased readmission rates compared with L [odds ratio (OR) 2.80, P = 0.021] or C (OR 13.89, P = 0.015). When combining initial and readmission LOS, C and IL groups had comparable overall LOS [median ratio (MR) 1.09, P = 0.57], which was significantly longer than in the L group (MR 1.27, P = 0.02). Conclusion: Extraction site enlargement during laparoscopic surgery for enteric Crohn's disease had no impact on primary LOS. However, the shorter initial LOS was offset by increased readmission rates when compared with formal conversion. The threshold to convert in case of anticipated difficulty due to a large specimen should be low