Irritable bowel syndrome(IBS)is the most prevalent functional gastrointestinal disorder.It is a multifactoria disorder.Intestinal microbiota may cause the pathogenesis of IBS by contributing to ...abnormal gastrointestina motility,low-grade inflammation,visceral hypersensitivity,communication in the gut-brain axis,and so on.Previous attempts to identify the intestinal microbiota composition in IBS patients have yielded inconsistent and occasionally contradictory results.This inconsistency may be due to the differences in the molecular techniques employed,the sample collection and handling methods,use of single samples that are not linked to fluctuating symptoms,or other factors such as patients diets and phenotypic characterizations.Despite these difficulties,previous studies found that the intestina microbiota in some IBS patients was completely different from that in healthy controls,and there does appear to be a consistent theme of Firmicutes enrichment and reduced abundance of Bacteroides.Based on the differences in intestinal microbiota composition,many studies have addressed the roles of microbiotatargeted treatments,such as antibiotics and probiotics,in alleviating certain symptoms of IBS.This review summarizes the current knowledge of the associations between intestinal microbiota and IBS as well as the possible modes of action of intestinal microbiota in the pathogenesis of IBS.Improving the current level of understanding of host-microbiota interactions in IBS is important not only for determining the role of intestinal microbiota in IBS pathogenesis but also for therapeutic modulation of the microbiota.
Summary
Background
Tegoprazan is a novel potassium‐competitive acid blocker that has a fast onset of action and can control gastric pH for a prolonged period, which could offer clinical benefit in ...acid‐related disorders.
Aim
To confirm the non‐inferiority of tegoprazan to esomeprazole in patients with erosive oesophagitis (EE).
Methods
In this multicentre, randomised, double‐blind, parallel‐group comparison study, 302 Korean patients with endoscopically confirmed EE (Los Angeles Classification Grades A‐D) were randomly allocated to either tegoprazan (50 or 100 mg) or esomeprazole (40 mg) treatment groups for 4 or 8 weeks. The primary endpoint was the cumulative proportion of patients with healed EE confirmed by endoscopy up to 8 weeks from treatment initiation. Symptoms, safety and tolerability were also assessed.
Results
The cumulative healing rates at week 8 were 98.9% (91/92), 98.9% (90/91) and 98.9% (87/88) for tegoprazan 50 mg, tegoprazan 100 mg and esomeprazole 40 mg, respectively. Both doses of tegoprazan were non‐inferior to esomeprazole 40 mg. The incidence of adverse events was comparable among the groups, and tegoprazan was well‐tolerated.
Conclusion
Once daily administration of tegoprazan 50 or 100 mg showed non‐inferior efficacy in healing EE and tolerability to that of esomeprazole 40 mg.
Abstract Purpose The human gut contains >100 trillion microbes. This microbiota plays a crucial role in the gut homeostasis. Importantly, the microbiota contributes to the development and regulation ...of the gut immune system. Dysbiosis of the gut microbiota could also cause several intestinal and extraintestinal diseases. Many experimental studies help us to understand the complex interplay between the host and microbiota. Methods This review presents our current understanding of the mucosal immune system and the role of gut microbiota for the development and functionality of the mucosal immunity, with a particular focus on gut-associated lymphoid tissues, mucosal barrier, TH 17 cells, regulatory T cells, innate lymphoid cells, dendritic cells, and IgA-producing B cells and plasma cells. Findings Comparative studies using germ-free and conventionally-raised animals reveal that the presence of microbiota is important for the development and regulation of innate and adaptive immune systems. The host-microbial symbiosis seems necessary for gut homeostasis. However, the precise mechanisms by which microbiota contributes to development and functionality of the immune system remain to be elucidated. Implications Understanding the complex interplay between the host and microbiota and further investigation of the host-microbiota relationship could provide us the insight into the therapeutic and/or preventive strategy for the disorders related to dysbiosis of the gut microbiota.
Summary
Background
Proton pump inhibitor (PPI) use may alter the gut microbiome and increase the risk of cholangitis. However, the association of PPI use with the risk of incident cholangitis has not ...been evaluated.
Aim
To evaluate whether PPI use was associated with a higher risk of cholangitis.
Methods
This cohort study included a nationwide representative sample of the Korean general population followed up for 10 years (1 January 2003 to 31 December 2013). PPI use was identified from treatment claims and considered as a time‐varying variable. Incident cholangitis was identified from hospitalisation and out‐patient visit claims.
Results
During 4 212 003 person‐years of follow‐up, 58,863 participants had at least one PPI prescription and 1 834 participants developed cholangitis. The age‐, sex‐, residential area‐ and income‐adjusted hazard ratio (HR) for incident cholangitis comparing PPI use with non‐use was 6.06 (95% CI, 4.64‐7.91). The association was essentially unchanged in fully adjusted models (HR 5.75; 95% CI, 4.39‐7.54). The risk was highest during PPI treatment and decreased gradually after PPI discontinuation (Ptrend <.001).
Conclusions
In this large cohort, PPI use was associated with an increased risk of cholangitis. Physicians prescribing PPIs should consider cholangitis as a potential complication of PPI use.
SUMMARY
Background
Tegoprazan is a novel potassium‐competitive acid blocker used to treat acid‐related disorders.
Aim
To compare tegoprazan 25 mg with lansoprazole 15 mg as maintenance therapy in ...healed erosive oesophagitis (EE)
Methods
In this phase 3, double‐blind, multi‐centre study, patients with endoscopically confirmed healed EE were randomised 1:1 to receive tegoprazan 25 mg or lansoprazole 15 mg once daily for up to 24 weeks. The primary efficacy endpoint was the endoscopic remission rate after 24 weeks. The secondary efficacy endpoint was the endoscopic remission rate after 12 weeks. Safety endpoints included adverse events, clinical laboratory results and serum gastrin and pepsinogen I/II levels.
Results
We randomised patients to tegoprazan 25 mg (n = 174) or lansoprazole 15 mg (n = 177). Most had mild EE (Los Angeles (LA) grade A: 57.3%, LA grade B: 37.3%). The endoscopic remission rate after 24 weeks was 90.6% with tegoprazan and 89.5% with lansoprazole. Tegoprazan was not inferior to lansoprazole for maintaining endoscopic remission at 24 weeks and 12 weeks. In subgroup analysis, tegoprazan 25 mg showed no significant difference in maintenance rate according to LA grade (p = 0.47). The maintenance effect of tegoprazan was consistent in CYP2C19 extensive metabolisers (p = 0.76). Increases in serum gastrin were not higher in tegoprazan‐treated than lansoprazole‐treated patients.
Conclusions
Tegoprazan 25 mg was non‐inferior to lansoprazole 15 mg in maintenance of healing of mild EE. In this study, tegoprazan had a similar safety profile to lansoprazole.
In this phase 3, double‐blind, multi‐centre study, patients with endoscopically confirmed healederosive oesophagitis were randomised 1:1 to receive tegoprazan 25 mg or lansoprazole 15 mg once daily for up to 24 weeks. The endoscopic remission rate after 24 weeks was 90.6% for the tegoprazan group and 89.5% for the lansoprazole group. Overall, tegoprazan was not inferior to lansoprazole for maintaining endoscopic remission rates at 24 weeks and 12 weeks, and was well tolerated during the maintenance period.
Background and Aim
Previous studies suggested an association between Helicobacter pylori infection and osteoporosis; however, large‐scale longitudinal studies are lacking to elucidate this ...association.
Methods
A cohort study of 10 482 women without osteoporosis at baseline who participated in a repeated health‐screening examination including an H. pylori‐specific immunoglobulin G antibody test was conducted to evaluate the association between H. pylori and osteoporosis development. Osteoporosis was diagnosed using dual‐energy X‐ray absorptiometry.
Results
During the 77 515.3 person‐years of follow‐up, women with H. pylori infection had a higher rate of incident osteoporosis than those who were uninfected. In a multivariable model adjusted for age, body mass index (BMI), menopausal status, smoking status, regular exercise, comorbidities (including hypertension, diabetes mellitus, dyslipidemia, stroke, or ischemic heart disease), and concomitant medications, the hazard ratio (HR) for incident osteoporosis in women with H. pylori infection compared with that in women without infection was 1.23 (95% confidence interval CI, 1.03–1.45). The association between H. pylori and osteopenia development was also evident. In the multivariable analysis, menopause (HR, 1.68; 95% CI, 1.31–2.16) and increasing age (HR, 1.07; 95% CI, 1.06–1.08) were identified as significant risk factors for osteoporosis, whereas higher BMI (HR, 0.84; 95% CI, 0.81–0.87) was a protective factor for the risk of osteoporosis.
Conclusions
In this cohort study, H. pylori infection was associated with an increased risk of osteoporosis, independent of risk factors and confounding factors.
Background
Previous studies have suggested a relationship between Helicobacter pylori infection and dyslipidemia; however, large‐scale longitudinal studies have not elucidated this association. This ...study assessed the longitudinal effects of H. pylori infection and eradication on lipid profiles in a large cohort.
Methods
This cohort study included 2,626 adults without dyslipidemia at baseline, who participated in a repeated, regular health‐screening examination, which included upper gastrointestinal endoscopy, between January 2009 and December 2018. The primary outcome was incident dyslipidemia at follow‐up.
Results
During the 10,324 person‐years of follow‐up, participants with persistent H. pylori infection had a higher incidence rate (130.5 per 1,000 person‐years) of dyslipidemia than those whose infections had been successfully controlled (98.1 per 1,000 person‐years). In a multivariable model adjusted for age, sex, waist circumference, smoking status, alcohol intake, and education level, the H. pylori eradication group was associated with a lower risk of dyslipidemia than the persistent group (HR, 0.85; 95% CI, 0.77–0.95; p = 0.004). The association persisted after further adjustment for baseline levels of low‐density and high‐density lipoprotein cholesterol (HR, 0.87; 95% CI, 0.79–0.97; p = 0.014).
Conclusions
H. pylori infection may play a pathophysiologic role in the development of dyslipidemia, whereas H. pylori eradication might decrease the risk of dyslipidemia.
Endoscopic submucosal dissection (ESD) has been widely accepted for treating superficial esophageal squamous cell carcinoma (SESCC). However, long-term outcomes of ESD and esophagectomy for SESCC ...have not been compared. We compared the clinical outcomes of ESD and esophagectomy in a matched cohort.
Patients who underwent ESD and esophagectomy for SESCC were included. We selected SESCCs without obvious submucosal invasion from the surgical database by reviewing endoscopic images. To minimize the effect of selection bias, propensity score matching was performed. Overall survival (OS), disease-specific survival (DSS), recurrence-free survival (RFS), and metachronous RFS were compared between the 2 groups. Adverse event rates were also compared.
In a matched cohort of 120 pairs, OS, DSS, and RFS were comparable between the 2 groups. The 5-year OS, DSS, and RFS rates were 93.9% versus 91.2%, 100% versus 97.4%, and 92.8% versus 95.3% for the ESD and esophagectomy groups, respectively. The metachronous RFS was worse in the ESD group than in the esophagectomy group (P = .004). The 5-year metachronous RFS rates were 90.3% versus 100% for the ESD and esophagectomy groups, respectively. The esophagectomy group showed a higher overall adverse event rate than the ESD group (55.5% vs 18.5%, P < .0001). In each subgroup of mucosal and submucosal cancer, OS, DSS, and RFS were also comparable between the 2 groups.
ESD provides long-term outcomes comparable with esophagectomy in patients with SESCC without endoscopic evidence of obvious submucosal invasion. ESD should be considered as the first-line treatment for these patients.
To suggest an appropriate surveillance strategy after curative endoscopic submucosal dissection (ESD) for early gastric cancers, based on incidence and patterns of local, metachronous, and ...extragastric recurrence.
Between 2003 and 2011, 1497 consecutive patients with 1539 differentiated-type early gastric cancers meeting absolute or expanded indication criteria underwent curative ESD. They were followed up with esophagogastroduodenoscopy (EGD) and abdominal computed tomography (CT) under a standardized surveillance protocol. Long-term outcomes were analyzed for 1306 patients with at least 1 year's follow-up.
Incidences of residual and synchronous lesions detected within 1 year were 0.13 % and 0.87 %, respectively. During median 47 months of follow-up, there was 1 local recurrence (0.08 %; early gastric cancer) and 47 cases of metachronous recurrence (3.6 %; 44 early gastric cancers, 3 pT2 advanced gastric cancers); all were curatively treated. During a 5-year surveillance, the cumulative incidence curve of metachronous recurrence increased linearly. Median time from ESD to metachronous recurrence was 30 months. There were 2 extragastric recurrences (0.15 %) in lymph nodes, at 5 and 4 years, respectively, after curative ESD for absolute and expanded indications. The patient with the expanded indications underwent a palliative operation and died of gastric cancer progression.
There was a constant incidence rate of metachronous recurrence during a 5-year surveillance period and there was extragastric recurrence at least 4 years after ESD of early gastric cancer even for absolute indications. Therefore, annual or biannual surveillance EGD and abdominal CT might be necessary for at least 5 years after curative ESD for early gastric cancers, with absolute as well as expanded indications.
Non‐technical summary What is known about gastric electrophysiology and used in motility clinics throughout the world is mostly deduced from animal studies and extracellular recordings from human ...patients. Extracellular recording from gastrointestinal muscles, however, is prone to extensive motion artifact, and it is not clear that animal models can be translated directly to human physiology. Therefore, we have performed a detailed analysis of electrical activity from carefully mapped specimens of gastric muscle removed from humans during surgery for gastric cancers. Our data show several important differences in electrical activity recorded with intracellular microelectrodes and accepted gastric electrophysiological dogma. We observed ongoing electrical slow wave activity in the gastric fundus; we also found no evidence for a slow wave frequency gradient. Muscles from all regions through the thickness of the muscularis demonstrated intrinsic pacemaker activity, and this corresponded with the widespread distribution of pacemaker cells.
Extracellular electrical recording and studies using animal models have helped establish important concepts of human gastric physiology. Accepted standards include electrical quiescence in the fundus, 3 cycles per minute (cpm) pacemaker activity in corpus and antrum, and a proximal‐to‐distal slow wave frequency gradient. We investigated slow wave pacemaker activity, contractions and distribution of interstitial cells of Cajal (ICC) in human gastric muscles. Muscles were obtained from patients undergoing gastric resection for cancer, and the anatomical locations of each specimen were mapped by the operating surgeon to 16 standardized regions of the stomach. Electrical slow waves were recorded with intracellular microelectrodes and contractions were recorded by isometric force techniques. Slow waves were routinely recorded from gastric fundus muscles. These events had similar waveforms as slow waves in more distal regions and were coupled to phasic contractions. Gastric slow wave frequency was significantly greater than 3 cpm in all regions of the stomach. Antral slow wave frequency often exceeded the highest frequency of pacemaker activity in the corpus. Chronotropic mechanisms such as muscarinic and prostaglandin receptor binding, stretch, extracelluar Ca2+ and temperature were unable to explain the observed slow wave frequency that exceeded accepted normal levels. Muscles from all regions through the thickness of the muscularis demonstrated intrinsic pacemaker activity, and this corresponded with the widespread distribution in ICC we mapped throughout the tunica muscularis. Our findings suggest that extracellular electrical recording has underestimated human slow wave frequency and mechanisms of human gastric function may differ from standard laboratory animal models.
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