Neri, Matteo

We sought to determine whether the proximal colon modifies its capacity to accommodate contents by altering the tone within its wall. In dogs equipped with manometric recorders in the terminal ileum and proximal colon, a highly compliant bag was introduced into the proximal colon. With the use of an electromechanical barostat, the capacity of the colonic segment was monitored at a constant low-distending pressure; the volume of air required to maintain a preset pressure in the bag was recorded by the barostat. During fasting, rhythmic cycles of volume were recorded, with a cycle frequency of approximately 1/min. Importantly, this phenomenon was not related to the simultaneous recording of manometric pressures in the adjacent bowel or to the interdigestive cycle (phase III) in the ileum. Peristaltic-like pressure complexes (recorded manometrically) in the ileocolonic region were associated with receptive relaxation of the proximal colon. Feeding, bethanechol, and morphine reduced volumes accommodated in the bag, presumably by increasing tone in the wall of the colon. Atropine had the opposite effect. These results support the concept that tonic changes in the wall of the proximal colon, which could influence accommodation and storage in the large bowel, are not always recorded by conventional techniques.

Our hypothesis was that the canine ileocolonic sphincter (ICS), per se, would have little regulatory effect on the transit of chyme from ileum to colon. We argued, from earlier observations, that the ileocolonic junction was influenced more by functional motor integration of the ileum, ICS, and proximal colon. In five dogs, the ileocolonic sphincter was ablated by extramucosal sphincterotomy; the operation significantly lowered tonic pressures at the ICS. Animals were then studied in the fasting state and postprandially. Ileal flow was estimated by marker dilution, and ileocolonic flow was estimated by total recovery of chyme from a colonic cannula. Transit times were measured after the bolus infusion of nonabsorbable markers. Ileocolonic sphincterotomy did not significantly alter flow rates or transit times of chyme across the ICS, although ileal motor patterns were changed after sphincterotomy. We concluded that the ICS probably has only a small effect on transit and flow at the ileocolonic junction. These findings argue for the importance of integrated motility of the ileum, ICS, and proximal colon in controlling the flow of chyme in this region.

We describe here further observations on a novel motor phenomenon that can be recorded regularly from the canine ileum in the late postprandial period, i.e., when residue of a meal reaches the distal small bowel. We reported before that this unique pattern of motility consisted of intraluminal pressure waves at a frequency (20-24/min) much greater than that of the ileal slow wave. In the current experiments, we document that these intraluminal pressure waves coincide with contraction of the circular muscle layer, as recorded from serosal strain gauges. However, the cellular origin and propagation of these contractile events are still unclear. By studying dogs with ileal loops and those with an intact bowel, we conclude that this is a local response of the ileum to the arrival of nutrients in its lumen and that it is under cholinergic control. This report supports the concept that the ileum may be particularly sensitive to its local intraluminal environment.

Objective IBS is a common gut disorder of uncertain pathogenesis. Among other factors, genetics and certain foods are proposed to contribute. Congenital sucrase–isomaltase deficiency (CSID) is a rare genetic form of disaccharide malabsorption characterised by diarrhoea, abdominal pain and bloating, which are features common to IBS. We tested sucrase–isomaltase ( SI ) gene variants for their potential relevance in IBS. Design We sequenced SI exons in seven familial cases, and screened four CSID mutations (p.Val557Gly, p.Gly1073Asp, p.Arg1124Ter and p.Phe1745Cys) and a common SI coding polymorphism (p.Val15Phe) in a multicentre cohort of 1887 cases and controls. We studied the effect of the 15Val to 15Phe substitution on SI function in vitro. We analysed p.Val15Phe genotype in relation to IBS status, stool frequency and faecal microbiota composition in 250 individuals from the general population. Results CSID mutations were more common in patients than asymptomatic controls (p=0.074; OR=1.84) and Exome Aggregation Consortium reference sequenced individuals (p=0.020; OR=1.57). 15Phe was detected in 6/7 sequenced familial cases, and increased IBS risk in case–control and population-based cohorts, with best evidence for diarrhoea phenotypes (combined p=0.00012; OR=1.36). In the population-based sample, 15Phe allele dosage correlated with stool frequency (p=0.026) and Parabacteroides faecal microbiota abundance (p=0.0024). The SI protein with 15Phe exhibited 35% reduced enzymatic activity in vitro compared with 15Val (p<0.05). Conclusions SI gene variants coding for disaccharidases with defective or reduced enzymatic activity predispose to IBS. This may help the identification of individuals at risk, and contribute to personalising treatment options in a subset of patients.