Several studies have reported a significant association between sleep disturbance and inflammatory bowel disease (IBD). The aim of the present study is to compare the clinical characteristics and the health-related quality of life (HR-QOL) of Japanese IBD patients with or without sleep disturbances, and to investigate the risk factors for disease flare in these patients. IBD patients were asked to complete a self-administered questionnaire including the Pittsburg sleep quality index and the 8-item short-form health survey. The information about disease flare within 1 year from enrollment in the study was analyzed with a multiple logistic regression model to identify risk factors for IBD flare-ups. The prevalence of sleep disturbances was 44.1 % (60 out of 136 IBD patients). Use of sleep medications was significantly higher in IBD patients with sleep disturbances whereas use of immuno modulators was significantly higher in IBD patients without sleep disturbances. The scores from all HR-QOL domains were significantly lower in patients with sleep disturbances than in patients without sleep disturbances. Fifty-one patients (37.5 %) had disease flare within 1 year from enrollment in the study and sleep disturbances were identified as a significant risk factor for disease flare (OR 3.09, 95 % CI 1.47–6.43). Our results indicate that sleep disturbances are common in Japanese IBD patients and are associated with poorer HR-QOL. Since the presence of sleep disturbances is a significant risk factor for IBD flare-ups, we encourage physicians to perform a careful examination of sleep disturbances in IBD patients.

Gastroesophageal reflux disease (GERD) is a common upper gastrointestinal disease. However, the role of exosomal microRNAs (miRNAs) and esophageal miRNAs in GERD has not been studied. A rat model of acid reflux esophagitis was used to establish a novel diagnosis marker for GERD and examine dynamics of miRNA expression in GERD. Rats were sacrificed 3 (acute phase), 7 (sub-acute phase) and 21 days (chronic phase) after induction of esophagitis. Exosomes were extracted from serum, and the expression patterns of serum miRNAs were analyzed. Four upregulated miRNAs (miR-29a-3p, 128-3p, 223-3p and 3473) were identified by microarray analysis. The expression levels of exosomal miR-29a-3p were significantly higher in the chronic phase of reflux esophagitis compared with controls, and increased expression of miR-29a-3p was specific to chronic reflux esophagitis. Esophageal miR-223-3p expression was higher compared with controls, and gradually decreased from acute to chronic phase in esophagitis. In conclusion, exosomal miR-29a-3p and esophageal miR-223-3p might play roles in GERD.

Approximately half of patients with eosinophilic esophagitis (EoE) respond clinically and histologically to proton pump inhibitor (PPI) therapy. Although recent guidelines suggest that PPI-responders and non-responders were included in EoE, it is important to investigate the predictive factors of PPI- responsiveness. This study aimed to determine the rate of PPI- responders and compare the characteristics of PPI-responders and non-responders. Fifty-nine patients with esophageal eosinophilia received PPI therapy for eight weeks, and its efficacy was assessed. PPI- responsiveness was diagnosed based on the relief in symptoms and reduction of intraepithelial eosinophilic infiltration to <15 per high-power field (hpf) after PPI therapy. Multivariate analysis was performed to identify factors associated with PPI-responders. Of the 59 patients, 41 (69.5%) were diagnosed with PPI-responders. The rate of gastrointestinal (GI) screening in the indications for endoscopy was significantly higher in patients with PPI- responders than in those with non-responders. On multivariate analysis, GI screening and presence of reflux esophagitis was associated with an increased odds ratio (OR) of PPI-responders, but presence of rings with a decreased OR of PPI-responders. Presence of reflux esophagitis and absence of rings on endoscopy especially during GI screening might be significant predictive factors for PPI response in patients with EoE.

Background and Aims: Gastroesophageal reflux disease (GERD) is strongly associated with sleep disturbances. Clock genes harmonize circadian rhythms by their periodic expression and regulate several physiological functions. However, the association between clock genes and GERD is still unknown. We investigated whether reflux esophagitis affects circadian variability of clock genes in the esophagus and other organs using a rat reflux esophagitis model. Methods: Reflux esophagitis was induced in 7-week-old male Wistar rats. Sham-operated rats were used as controls. Rats were sacrificed at 09:00 (light period) and 21:00 (dark period) 3 days (acute phase) and 21 days (chronic phase) after induction of esophagitis. The expression levels of clock gene mRNAs such as Per1, Per2, Per3, Cry1, Cry2, Arntl, and Clock in the esophagus were investigated by qPCR. Arntl expression was examined in stomach, small intestine, colon, and liver tissues. Serum melatonin and IL-6 levels were measured by ELISA. Results: Histological examination of reflux esophagitis mainly revealed epithelial defects with marked inflammatory cell infiltration in the acute phase, and mucosal thickening with basal cell hyperplasia in the chronic phase. Circadian variability of clock genes, except Cry1, was present in the normal esophagus, and was completely disrupted in reflux esophagitis during the acute phase. The circadian variability of Per2, Per3, and Arntl returned to normal, but disruption of Per1, Cry2, and Clock was present in the chronic phase. Disruption of circadian variability of Arntl was observed in the esophagus, as well as in the stomach, small intestine, and liver tissues in reflux esophagitis during the acute phase. There were no significant differences in serum melatonin and IL-6 levels between control and reflux esophagitis animals in both acute and chronic phases. Conclusion: Disruption to circadian variability of clock genes may play a role in the pathogenesis of GERD.