ICC density predicts bacterial overgrowth in a rat model of post-infectious IBS

AIM:To investigate the interstitial cells of Cajal(ICC) number using a new rat model.METHODS:Sprague-Dawley rats were assigned to two groups.The first group received gavage with Campylobacter jejuni(C.jejuni) 81-176.The second group was gavaged with placebo.Three months after clearance of Campylobacter from the stool,precise segments of duodenum,jejunum,and ileum were ligated in self-contained loops of bowel that were preserved in anaerobic bags.Deep muscular plexus ICC(DMP-ICC) were quantified by two blinded readers assessing the tissue in a random,coded order.The number of ICC per villus was compared among controls,Campylobacter recovered rats without small intestinal bacterial overgrowth(SIBO),and Campylobacter recovered rats with SIBO.RESULTS:Three months after recovery,27% of rats gavaged with C.jejuni had SIBO.The rats with SIBO had a lower number of DMP-ICC than controls in the jejunum and ileum.Additionally there appeared to be a density threshold of 0.12 DMP-ICC/villus that was associated with SIBO.If ileal density of DMP-ICC was < 0.12 ICC/villus,54% of rats had SIBO compared to 9% among ileal sections with > 0.12(P<0.05).If the density of ICC was < 0.12 DMP-ICC/villus in more than one location of the bowel,88% of these had SIBO compared to 6% in those who did not(P<0.001).CONCLUSION:In this post-infectious rat model,the development of SIBO appears to be associated with a reduction in DMP-ICC.Further study of this rat model might help understand the pathophysiology of postinfectious irritable bowel syndrome.

Effect of electrical stimulation of the lower esophageal sphincter in gastroesophageal reflux disease patients refractory to proton pump inhibitors

AIM: To evaluate the efficacy of lower esophageal sphincter(LES)-electrical stimulation therapy(EST) in a subgroup of patients that reported only partial response to proton pump inhibitors(PPIs) therapy, compared to a group of patient with complete response.METHODS: Bipolar stitch electrodes were laparoscopically placed in the LES and connected to an implantable pulse generator(EndoS tim BV, the Hague, the Netherlands), placed subcutaneously in the anterior abdominal wall. Stimulation at 20 Hz, 215 μsec, 3-8 m Amp in 30 min sessions was delivered starting on day 1 post-implant. Patients were evaluated using gastroesophageal reflux disease(GERD)-HRQL, symptom diaries; esophageal p H and esophageal manometry before and up to 24 mo after therapy and results were compared between partial and complete responders.RESULTS: Twenty-three patients with GERD on LESEST were enrolled and received continuous per-protocol stimulation through 12 mo and 21 patients completed 24 mo of therapy. Of the 23 patients, 16(8 male, mean age 52.1 ± 12 years) had incomplete response to PPIs prior to LES-EST, while 7 patients(5 male, mean age 52.7 ± 4.7) had complete response to PPIs. In the sub-group with incomplete response to PPIs, median(IQR) composite GERD-HRQL score improved significantly from 9.5(9.0-10.0) at baseline on-PPI and 24.0(20.8-26.3) at baseline off-PPI to 2.5(0.0-4.0) at 12-mo and 0.0(0.0-2.5) at 24-mo follow-up(P < 0.05 compared to on-and off-PPI at baseline). Median(IQR) % 24-h esophageal pH < 4.0 at baseline in this sub-group improved significantly from 9.8%(7.8-11.5) at baseline to 3.0%(1.9-6.3) at 12 mo(P < 0.001) and 4.6%(2.0-5.8) at 24 mo follow-up(P < 0.01). At their 24-mo follow-up, 9/11 patients in this sub-group were completely free of PPI use. These results were comparable to the sub-group that reported complete response to PPI therapy at baseline. No unanticipated implantation or stimulation-related adverse events, or any untoward sensation due to stimulation were reported in either group and LES-EST was safely tolerated by both groups. CONCLUSION: LES-EST is safe and effective in controlling symptoms and esophageal acid exposure in GERD patients with incomplete response to PPIs. These results were comparable to those observed PPI responders.