5-Aminosalicylic acid alters the gut microbiota and altered microbiota transmitted vertically to offspring have protective effects against colitis.

Although many therapeutic options are available for inflammatory bowel disease (IBD), 5-aminosalicylic acid (5-ASA) is still the key medication, particularly for ulcerative colitis (UC). However, the mechanism of action of 5-ASA remains unclear. The intestinal microbiota plays an important role in the pathophysiology of IBD, and we hypothesized that 5-ASA alters the intestinal microbiota, which promotes the anti-inflammatory effect of 5-ASA. Because intestinal inflammation affects the gut microbiota and 5-ASA can change the severity of inflammation, assessing the impact of inflammation and 5-ASA on the gut microbiota is not feasible in a clinical study of patients with UC. Therefore, we undertook a translational study to demonstrate a causal link between 5-ASA administration and alterations of the intestinal microbiota. Furthermore, by rigorously controlling environmental confounders and excluding the effect of 5-ASA itself with a vertical transmission model, we observed that the gut microbiota altered by 5-ASA affected host mucosal immunity and decreased susceptibility to dextran sulfate sodium-induce colitis. Although the potential intergenerational transmission of epigenetic changes needs to be considered in this study, these findings suggested that alterations in the intestinal microbiota induced by 5-ASA directed the host immune system towards an anti-inflammatory state, which underlies the mechanism of 5-ASA efficacy.

Comparison of endoscopic band ligation devices used for colonic diverticular bleeding: in vivo animal study.

BACKGROUND AND AIM: Endoscopic band ligation (EBL), used for the treatment of colonic diverticular bleeding, has a lower rebleeding rate than endoscopic clipping. However, different devices are used in Japan and the Western countries; no animal studies have been conducted to elucidate the safety of such devices. We compared two EBL devices, the first used in Japan and the second used in Western countries. METHODS AND RESULTS: The Japanese and Western EBL devices were compared by assessing the EBL safety at 40 sites in an animal model with a normal colon that is anatomically similar to the human colon. Macroscopic and pathological examinations were performed to evaluate the layer ligated by the band and the presence of perforation. The findings on day 1 and day 7 after EBL were compared. The ligated layer was the muscularis propria at 39 sites; the layer was not evaluated at one site where the band was unintentionally removed during the endoscopic procedure. Pathologically, there was no perforation at any of the assessed sites. There was no statistical difference in any of the pathological variables between the two devices or between days 1 and 7 after EBL. The total procedure time was significantly shorter with the Western EBL device. CONCLUSIONS: In this animal study, both evaluated devices were safe for EBL, without differences in the macroscopic and pathological variables after EBL. Ligation of the muscularis propria layer did not result in perforation.

Endoscopic Doppler probe ultrasonography for detecting blood flow at post-endoscopic submucosal dissection ulcers of the stomach.

Background and study aims The rate of early rebleeding after endoscopic submucosal dissection (ESD) for early gastric cancer ranges from 5 % to 38 %, despite application of preventive methods. Post-ESD rebleeding may be caused by "invisible" vessels that may not be detectable using ultrasonographic techniques. Recently, Doppler probe ultrasonography (DOP) has been used in endoscopy. Because little is known about the usefulness of DOP for decreasing the post-ESD rebleeding rate, we performed a preliminary case series study. Patients and methods Twelve patients underwent DOP for post-ESD ulcer evaluation after visible vessel coagulation. In this study, the novel DOP system used in the vascular surgery department was used. DOP-positive invisible vessels were shown as a pulse wave on the monitor. Results No (0 %) cases of post-ESD rebleeding occurred. Twenty invisible vessels were detected, and 13 were subjected to additional coagulation up to a depth of 3 mm. Mean DOP procedure time was 11.6 minutes (range: 8-18 minutes). In these latter cases, disappearance of the Doppler pulse wave was confirmed. No early rebleeding or other adverse events were experienced. Conclusion DOP is a safe and feasible method for detecting invisible vessels in post-ESD ulcers. Further investigation of the clinical relevance is warranted.

Effectiveness of risk scoring systems in predicting endoscopic treatment in colonic diverticular bleeding.

BACKGROUND AND AIMS: The identification of stigmata of recent hemorrhage (SRH) in colonic diverticular bleeding (CDB) enables an endoscopic treatment and can improve the clinical outcome. However, SRH identification rate remains low. This study aims to investigate whether NOBLADS and Strate scoring systems are useful for predicting SRH identification rate of CDB pre-procedurally via colonoscopy. METHODS: In this single-center retrospective observational study, 302 patients who experienced their first episode of CDB from April 2008 to March 2018 were included. Patients were classified into SRH-positive and SRH-negative groups. The primary outcome was SRH identification rate. The secondary outcomes were active bleeding in SRH and early rebleeding rates. The usefulness of the NOBLADS and Strate scores as predicted values of SRH identification was evaluated using the area under the receiver operating characteristic curve. RESULTS: There were 126 and 176 patients in the SRH-positive and SRH-negative groups, respectively. The area under the receiver operating characteristic curve for SRH identification using the NOBLADS score was 0.74 (95% confidence interval, 0.69-0.80) and that using the Strate score was 0.74 (95% confidence interval, 0.68-0.79). Active bleeding and early rebleeding rates increased according to each score. By setting the cut-off of the NOBLADS score to four points, treatment was possible in 70.2% (66/94) patients. Addition of extravasation at computed tomography to a NOBLADS score of ≧ 4 points allowed treatment of all patients (24/24). CONCLUSIONS: Severity scoring in acute lower gastrointestinal bleeding was effective for predicting SRH identification in CDB. We suggest that combination of these scorings and CT findings could offer a new therapeutic strategy.

Community-acquired fulminant colitis caused by binary toxin-producing Clostridium difficile in Japan.

We report a case of community-acquired fulminant colitis caused by Clostridium difficile in Japan. A 46-year-old woman was diagnosed with severe infectious enterocolitis and was admitted at another hospital. The stool culture was positive for toxigenic C. difficile. Since the patient presented with fulminant C. difficile infection (CDI) with toxic megacolon, respiratory insufficiency, and circulatory failure, she was transferred to Kyorin University Hospital for intensive care. Intubation and antibiotic therapy were performed. The general condition improved with conservative treatment, and she was discharged without sequelae. While the recovered isolate was toxin A and B-positive and binary toxin-positive, it was identified as polymerase chain reaction (PCR) ribotype ts0592 and slpA sequence type ts0592. The isolate was different from PCR ribotype 027 epidemic in Europe and North America. In Japan, binary toxin-producing strains are rare and have not caused an epidemic to date. Furthermore, there are few data on community-acquired CDI in Japan. In this case, a non-elderly woman with no major risk factors such as antibiotic use, administration of proton pump inhibitor and history of gastrointestinal surgery developed community-acquired fulminant CDI caused by the binary toxin-positive strain, and ICU treatment was required. Further studies focusing on the role of binary toxin-positive C. difficile in the severity of community-acquired CDI are necessary.