Nationwide multicenter study on adverse events associated with a patency capsule: Additional survey of appropriate use of patency capsule study.

BACKGROUND AND AIM: The PillCam patency capsule (PC) without a radio frequency identification tag was released to preclude retention of the small bowel capsule endoscope (CE) in Japan in 2012. We conducted a multicenter study to determine tag-less PC-related adverse events (AEs). METHODS: We first conducted a retrospective survey using a standardized data collection sheet for the clinical characteristics of PC-related AEs among 1096 patients collected in a prospective survey conducted between January 2013 and May 2014 (Cohort 1). Next, we retrospectively investigated additional AEs that occurred before and after Cohort 1 within the period June 2012 and December 2014 among 1482 patients (Cohort 2). RESULTS: Of the 2578 patients who underwent PC examinations from both cohorts, 74 AEs occurred among 61 patients (2.37%). The main AEs were residual parylene coating in 25 events (0.97%), PC-induced small bowel obstruction, suspicious of impaction, in 23 events (0.89%), and CE retention even after patency confirmation in 10 events (0.39%). Residual parylene coating was significantly associated with Crohn's disease (P < 0.01). Small bowel obstruction was significantly associated with physicians with less than 1 year of experience handling the PC and previous history of postprandial abdominal pain (P < 0.01 and P < 0.03, respectively). CE retention was ascribed to erroneous judgment of PC localization in all cases. CONCLUSIONS: This large-scale multicenter study provides evidence supporting the safety and efficiency of a PC to preclude CE retention. Accurate PC localization in patients without excretion and confirmation of previous history of postprandial abdominal pain before PC examinations is warranted (UMIN000010513).

Current Status of Diagnosis and Treatment of Colorectal Cancer in Asian Countries: A Questionnaire Survey.

INTRODUCTION: Diagnostic and therapeutic methods for colorectal cancer (CRC) have advanced; however, they may be inaccessible worldwide, and their widespread use is challenging. This questionnaire survey investigates the current status of diagnosis and treatment of early-stage CRC in Asian countries. METHODS: Responses to the questionnaire were obtained from 213 doctors at different institutions in 8 countries and regions. The questionnaire consisted of 39 questions on the following four topics: noninvasive diagnosis other than endoscopy (6 questions), diagnosis by magnification and image-enhanced endoscopy (IEE) including artificial intelligence (AI) (10 questions), endoscopic submucosal dissection (ESD), proper use among other therapeutic methods (11 questions), and pathologic diagnosis and surveillance (12 questions). RESULTS: Although 101 of 213 respondents were affiliated with academic hospitals, there were disparities among countries and regions in the dissemination of advanced technologies, such as IEE, AI, and ESD. The NICE classification is widely used for the diagnosis of colorectal tumors using IEE, while the JNET classification with magnification was used in countries such as Japan (65/70, 92.9%) and China (16/22, 72.7%). Of the 211 respondents, 208 (98.6%) assumed that en bloc resection should be achieved for carcinomas, and 180 of 212 (84.9%) believed that ESD was the most suitable in cases with a diameter larger than 2 cm. However, colorectal ESD is not widespread in countries such as Thailand, the Philippines, and Indonesia. CONCLUSION: The promotion of advanced technologies and education should be continual to enable more people to benefit from them.

Background factors of idiopathic peptic ulcers and optimal treatment methods: a multicenter retrospective Japanese study.

This study investigated the trends in idiopathic peptic ulcers, examined the characteristics of refractory idiopathic peptic ulcer, and identified the optimal treatment. The characteristics of 309 patients with idiopathic peptic ulcer were examined. We allocated idiopathic peptic ulcers that did not heal after 8 weeks' treatment (6 weeks for duodenal ulcers) to the refractory group and those that healed within this period to the healed group. The typical risk factors for idiopathic peptic ulcer (atherosclerosis-related underlying disease or liver cirrhosis complications) were absent in 46.6% of patients. Absence of gastric mucosal atrophy (refractory group: 51.4%, healed group: 28.4%; p = 0.016), and gastric fundic gland polyps (refractory group: 17.6%, healed group: 5.9%; p = 0.045) were significantly more common in the refractory group compared to the healed group. A history of H. pylori eradication (refractory group: 85.3%, healed group: 66.0%; p = 0.016), previous H. pylori infection (i.e., gastric mucosal atrophy or history of H. pylori eradication) (refractory group: 48.5%, healed group: 80.0%; p = 0.001), and potassium-competitive acid blocker treatment (refractory group: 28.6%, healed group, 64.1%; p = 0.001) were significantly more frequent in the healed group compared to the refractory group. Thus, acid hypersecretion may be a major factor underlying the refractoriness of idiopathic peptic ulcer.

Astaxanthin attenuated the stress-induced intestinal motility disorder via altering the gut microbiota.

Gut microbiota and short-chain fatty acids (SCFAs) are recognized as key factors in the pathophysiology of irritable bowel syndrome. Astaxanthin is a carotenoid with strong antioxidant and anti-inflammatory activities. In this study, we examined the effects of astaxanthin on gut microbiota-, SCFAs-, and corticotropin-releasing factor (CRH)-induced intestinal hypermotility. Male Wistar rats (n=12 per group) were fed a diet with or without 0. 02% (w/w) astaxanthin for four weeks and CRH or saline was administered intravenously. The number of fecal pellets was counted 2 h after injection. Then the rats were sacrificed, and the cecal content were collected 3 h after injection. The number of feces was significantly increased by CRH injection in the control group (2.0 vs. 6.5; p=0.028), but not in the astaxanthin group (1.0 vs. 2.2; p=0.229) (n=6 per group). The cecal microbiota in the astaxanthin group was significantly altered compared with that in the control group. The concentrations of acetic acid (81.1 µmol/g vs. 103.9 µmol/g; p=0.015) and butyric acid (13.4 µmol/g vs. 39.2 µmol/g; p<0.001) in the astaxanthin group were significantly lower than that in the control group (n=12 per group). Astaxanthin attenuates CRH-induced intestinal hypermotility and alters the composition of gut microbiota and SCFAs.

Reduced abundance of butyric acid-producing bacteria in the ileal mucosa-associated microbiota of ulcerative colitis patients.

Compositional changes in the microbiota are associated with various inflammatory diseases, including ulcerative colitis (UC). Aim: This study aimed to investigate the mucosa-associated microbiota (MAM) in patients with UC and its difference related with disease activity and classification. Brush samples were collected from the terminal ileum and sigmoid colon during endoscopic procedures. The microbiota of samples was profiled using the Illumina MiSeq platform. The V3-V4 regions of the gene encoding 16S rRNA (460 bp) were amplified using PCR. Fifty UC patients and twenty healthy controls were enrolled. UC patients displayed significantly reduced α-diversity in both the ileum and sigmoid colon compared to controls. A difference in ß-diversity in the unweighted analysis was observed between the two groups. The abundance of Lactobacillus and Veillonella was significantly higher and that of Butyricicoccus, Ruminococcus and Lachnospiraceae was significantly lower in the ileum of UC patients than in controls. The abundance of Odoribacter in the ileum was significantly lower in left-sided colitis and pancolitis patients than in proctitis patients and lower in patients with highly severe disease activity than with mild disease activity. The reduction in abundance of butyric acid-producing bacteria, especially Odoribacter, in ileal MAM may play an important role in the pathophysiology of UC.

Comparison of mucosa-associated microbiota in Crohn's disease patients with and without anti-tumor necrosis factor-α therapy.

Most studies on the gut microbiome of Crohn's disease have been conducted using feces, instead of intestinal mucus to analyze the mucosa-associated microbiota. To investigate the characteristics of mucosa-associated microbiota in Crohn's disease patients and the effect of anti-tumor necrosis factor (TNF)-α therapy on mucosa-associated microbiota, we analyzed microbiota in Crohn's disease patients using brushing samples taken from terminal ileum. The recruited subjects were 18 Crohn's disease patients and 13 controls. There were 10 patients with anti-TNF-α therapy in Crohn's disease group. Crohn's disease patients had significantly reduced α-diversity in Shannon index compared to the controls. The comparative analysis of the taxonomic composition at the genus level between the Crohn's disease group and the controls indicated that butyrate-producing bacteria were less abundant in the Crohn's disease group compared to the controls. There were no differences in the diversity between the patients taking anti-TNF-α therapy and the patients without. The comparative analysis of the taxonomic composition at the genus level between the two groups indicated that some of anti-inflammatory bacteria were less abundant in the anti-TNF-α therapy group than the other. Reduction of specific bacteria producing anti-inflammatory molecules, especially butyrate-producing bacteria may play important roles in the pathophysiology of Crohn's disease.

Evaluation of efficacy and safety of lubiprostone in patients with chronic constipation.

OBJECTIVES: Lubiprostone is an apical type 2 chloride channel activator approved for the treatment of chronic constipation (CC), and nausea is the most common adverse symptom. However, the associated factors with the efficacy and the precise mechanism of nausea remain unclear. The aim of this study is to characterize clinical backgrounds related with the efficacy and the adverse symptoms of lubiprostone. MATERIALS AND METHODS: Subjects were patients with CC who were prescribed lubiprostone from April 2017 to October 2019. The efficacy and safety of lubiprostone were retrospectively examined using the electronic medical record. RESULTS: Hundred and fifty-five patients (76 men, and mean age 69) were evaluated. Lubiprostone was effective in 74 patients (47.8%), and the discontinuation due to adverse in 34 patients (21.9%). including nausea, diarrhea and abdominal pain in 16, 12 and 3 patients, respectively. The efficacy was significantly associated with gender, age, body mass index (BMI), diabetes mellitus, hypertension, calcium channel blockers and antipsychotics. In multivariate analysis, the efficacy was significantly associated with men (odds ratio [OR], 3.21; 95% confidence interval (CI), 1.42-7.27) and BMI (OR, 1.14; 95% CI, 1.02-1.28). The incidence of nausea was higher in patients under 65 years old, and hypertension was the significant protective factor for nausea. CONCLUSIONS: Lubiprostone was effective for men patients with CC, and hypertension seems to be the protective factor for nausea.

Efficacy and Feasibility of Magnifying Blue Laser Imaging without Biopsy Confirmation for the Diagnosis of the Demarcation of Gastric Tumors: A Randomized Controlled Study.

BACKGROUND: Accurate diagnosis of the demarcation line (DL) of gastric tumors is essential for curative complete resection by endoscopic submucosal dissection (ESD). It is controversial to perform only magnifying endoscopy for diagnosing the DL of gastric tumors prior to ESD. This study aimed to evaluate the diagnostic accuracy for the DL of gastric adenomas and well-differentiated adenocarcinomas using only magnifying blue laser imaging (M-BLI) compared with that using both M-BLI and biopsy confirmation. METHODS: In this prospective, single-center study, 96 well-differentiated adenocarcinomas and 32 gastric adenomas were enrolled between July 2015 and December 2016. A total of 122 lesions with a clear DL on M-BLI were randomly allocated to undergo M-BLI only (the M-BLI group) or M-BLI with biopsy confirmation (the M-BLI-BC group), performed as biopsies in 4 directions from noncancerous tissues ≈ 5 mm outside the lesion before ESD. The primary end point was to clarify the noninferiority of M-BLI without biopsy confirmation compared with that with biopsy confirmation, in terms of the diagnostic accuracy and complete resection. RESULTS: There were no significant differences in sex, median age, color, circumference, macroscopic type, biopsy-based diagnosis, and Helicobacter pylori infection between the 2 groups. The diagnostic accuracy for the DL was 100 and 95.0% and the complete resection was 100 and 100% in the M-BLI and M-BLI-BC groups, respectively. CONCLUSION: The diagnostic ability of M-BLI is excellent in diagnosing the demarcation of gastric adenoma and well-differentiated adenocarcinoma. Biopsy confirmation is not needed for these lesions with a clear DL by M-BLI.

Mucosa-Associated Microbiota in Patients with Irritable Bowel Syndrome: A Comparison of Subtypes.

BACKGROUND: Most studies on gut microbiome of irritable bowel syndrome (IBS) have focused on fecal microbiota, instead of mucosa-associated microbiota (MAM). AIMS: The aim of this study wasto investigate the MAM in IBS patients including the difference in subtypes of IBS, namely, diarrhea-predominant IBS (IBS-D) and constipation-predominant IBS (IBS-C). METHODS: Endoscopic brush samples were taken from terminal ileum and sigmoid colon of patients with IBS (17 IBS-D patients and 7 IBS-C patients) and 10 healthy controls. The MAM of samples was profiled by 16S rRNA gene amplicon sequencing. Potential changes in the MAM at the functional level were evaluated using PICRUSt software and the KEGG database. RESULTS: There were no differences in MAM composition between terminal ileum and sigmoid colon according to ß-diversity based on the UniFrac distance. In view of α-diversity, Shannon (evenness) but not Chao1 (richness) or observed operational taxonomic units tended to be lower in sigmoid colon MAM of IBS-C and IBS-D than the control group. The abundance of 4 genera in the sigmoid colon and 7 genera in the terminal ileum was significantly different among the 3 groups. Linear discriminant analysis effect size (LEfSe) showed that the genera of Ruminococcus, Akkermansia, Butyrivibrio, Methylobacterium, and Microbacterium and the family Erysipelotrichaceae were significantly higher in the IBS-C group, and the abundance of the genera Streptococcus, Acidaminococcus, Butyricicoccus, and Parvimonas was significantly higher in the IBS-D group. In addition, the proportion of genes responsible for the secretion system and LPS biosynthesis was significantly higher and that for methane metabolism, lysine biosynthesis, and enzyme families was significantly lower in the IBS-D group than in the IBS-C group. CONCLUSION: Dysbiosis pattern and the function of the microbiome seem to be different among subtypes of IBS, and MAM may play a crucial role in IBS symptom generation.

Diagnostic Ability of Magnifying Blue Light Imaging with a Light Emitting Diode Light Source for Early Gastric Cancer: A Prospective Comparative Study.

INTRODUCTION: An innovative endoscopic system using 4-color light-emitting diodes (LED) was released between 2016 and 2017 in locations that had not approved laser endoscopes for use, including the United States and Europe. OBJECTIVE: This study compared the diagnostic efficacy between magnifying blue light imaging with an LED light source (LED-BLI) and magnifying blue laser imaging with a laser light source (Laser-BLI) for early gastric cancer (EGC). METHODS: In this prospective, single-center, noninferiority study, 80 gastric lesions were evaluated between January 2017 and July 2017. The magnifying findings of gastric lesions - including the demarcation line (DL), microvascular pattern (MVP), and microsurface pattern (MSP) - were evaluated using Laser-BLI and LED-BLI according to the vessel plus surface classification system (VSCS). The primary end point was to determine whether the diagnostic accuracy of LED-BLI for EGC was noninferior to that of conventional Laser-BLI. RESULTS: Overall, we evaluated 79 gastric lesions histopathologically diagnosed as adenocarcinomas from the specimens obtained via endoscopic submucosal dissection. A DL was observed by Laser-BLI and LED-BLI in 98.7% (78/79) and 96.2% (76/79) of EGCs, respectively. The MVP observed using Laser-BLI and LED-BLI was irregular in 92.4% (73/79) and 89.9% (71/79), respectively. The MSP observed using Laser-BLI and LED-BLI was irregular in 83.5% (66/79) and 82.2% (65/79), respectively. According to the VSCS, diagnosable cancers were found in 94.9% (75/79) and 93.7% (74/79) of cases when using Laser-BLI and LED-BLI, respectively (p = 0.73; difference ratio, 1.2%; 95% CI -8.5 to 6.0%). CONCLUSIONS: LED-BLI could accurately visualize the DL, MVP, and MSP of EGCs and was not inferior to Laser-BLI. Therefore, LED-BLI can be used to diagnose EGC accurately according to the VSCS-based diagnosis criteria.

Therapeutic Potential of Astaxanthin in Diabetic Kidney Disease.

Astaxanthin is a carotenoid that has potent protective effects on diabetic kidney disease (DKD) in diabetic mice models. DNA microarray study clearly demonstrated the involvement of mitochondrial oxidative phosphorylation pathway in the renal glomerular cells of diabetic mice and also showed that the expression of upregulated genes associated with this pathway was decreased by the treatment with astaxanthin. Proteomic analysis confirmed that the increases of 4-hydroxy-2-nonenal (HNE)- and Nε-(hexanonyl)lysine (HEL)-modified proteins were inhibited by the treatment with astaxanthin. These results demonstrated that astaxanthin exerts a protective effect against hyperglycemia-induced DKD by attenuating mitochondrial oxidative stress and subsequent cellular dysfunction.

PDZK1 induces resistance to apoptosis in esophageal adenocarcinoma cells.

BACKGROUND: Esophageal cancer is a lethal malignancy with a poor prognosis. The incidence of esophageal adenocarcinoma, which develops from Barrett's esophagus (BE), has recently been increasing. In a previous study, we found that PDZK1 expression is higher in long segment BE compared to that in short-segment BE. However, the function of PDZK1 in the mucosa of BE is unclear. AIMS: Clarify the role of PDZK1 in BE mucosa using PDZK1 overexpressed cells. METHODS: Human adenocarcinoma-derived OE33 cells were used as a parental cell line and transfected to generate PDZK1 overexpressed OE33 cells (PC cells) or transfected with empty vector as control cells (NC cells). Cell growth of NC and PC cells in 10% fetal bovine serum was evaluated by cell counting. The effect of PDZK1 on proteasome inhibitor (PSI)-induced apoptosis was qualified by fluorescence microscopy and quantified by flow cytometry. Expression of apoptosis-related proteins was evaluated by western blotting. RESULTS: There were no significant differences in cell growth between NC and PC cells. PSI significantly increased apoptosis in NC cells, but not in PC cells. In response to PSI, increased levels of cleaved-caspase3 and decreased pro-caspase3 levels were found in NC cells, but not in PC cells. In NC cells, PSI significantly decreased Bcl-2 expression without affecting Bax levels. In contrast, high expression of both Bcl-2 and Bax was observed in PC cells. CONCLUSION: Overexpression of PDZK1 protein induces an apoptosis-resistant phenotype in BE cells, which may be a potential therapeutic target.

Molecular biomarker identification for esophageal adenocarcinoma using endoscopic brushing and magnified endoscopy.

BACKGROUND: Barrett's esophagus (BE) is a predisposing factor for esophageal adenocarcinoma (EAC); however, the precise mechanism underlying this association remains unclear. The identification of biomarkers that are associated with an increased risk of BE progression to EAC would facilitate diagnosis and early treatment. Toward this goal, we aimed to identify biomarkers associated with BE and EAC in patients. METHODS: In conjunction with high-resolution magnified endoscopy with narrow-band imaging (ME-NBI), we obtained brushing samples from the long-segment BE (LSBE) or short-segment BE (SSBE) of patients with EAC or without EAC (control). To identify candidate biomarker genes, microarray analysis was performed for a training set of 28 American samples. To confirm the microarray results, expression levels of the 16 candidate biomarkers were evaluated by real-time polymerase chain reaction analysis, using samples collected from an additional 53 American patients. In addition, we also performed a functional analysis for these genes using Gene Ontology (GO) enrichment analysis. RESULTS: Among the 16 genes identified as differentially expressed by microarray analysis, the GO analysis indicated matrix metalloproteinase (MMP) family associated with 'collagen metabolic process' and 'multicellular organismal macromolecule metabolic process' as the two top biological processes. Brushing samples of patients with EAC showed up-regulated expression of decay-accelerating factors (DAF and CD55) and topoisomerase type Iiα (TOP2A), and down-regulated expression of the sodium channel epithelial 1 beta subunit (SCNN1B). CONCLUSIONS: The up-regulation of CD55 and TOP2A, and the down-regulation of SCNN1B were common to the brushing samples and might serve as molecular biomarkers for identifying EAC in patients with SSBE. TRIAL REGISTRATION: University Hospital Medical Information Network (UMIN) (000004004).

Helicobacter pylori eradication therapy outcome according to clarithromycin susceptibility testing in Japan.

BACKGROUND: Helicobacter pylori (Hp) infection increases the risk of gastric cancer. Therefore, eradication is a global goal, which requires continuous monitoring of therapeutic regimens and effectiveness. Clarithromycin resistance is an important contributor to eradication failure, and metronidazole is recommended as second-line treatment in such cases. Here, we retrospectively evaluated the clarithromycin and metronidazole resistance rates and treatment effectiveness in patients with Hp using tailored therapies according to clarithromycin susceptibility testing. METHODS: Data on drug susceptibility were obtained for 5249 Japanese Hp patients between July 2005 and August 2018. Clarithromycin/metronidazole resistance rates were analyzed according to year, gender, and age with Fisher's exact test. The relationship between clarithromycin resistance and Hp therapy outcomes was assessed for 1300 patients. Treatment regimens included a clarithromycin- or metronidazole-containing 7-day triple therapy with one of several proton pump inhibitors and vonoprazan. RESULTS: Clarithromycin resistance increased annually and was higher in women and younger patients (<30 years). Rates of metronidazole resistance were stable but decreased with age. Hp treatment regimens using PPIs had eradication rates of 88% and 45% among clarithromycin-sensitive and clarithromycin-resistant cases, respectively, while regimens including vonoprazan had eradication rates of around 90% regardless of clarithromycin susceptibility. In particular, triple therapy with vonoprazan, amoxicillin, and metronidazole achieved 98% eradication. CONCLUSION: Clarithromycin-containing triple therapy even using vonoprazan did not achieve satisfactory eradication rates even in the clarithromycin-sensitive group. To avoid antibiotic misuse in population with low metronidazole resistance, 7-day vonoprazan, amoxicillin, and metronidazole triple therapy might be a strong candidate as a first-line eradication therapy.

Promotion of wound healing by acetate in murine colonic epithelial cell via c-Jun N-terminal kinase activation.

BACKGROUND AND AIM: Mucosal healing is an important clinical goal in patients with inflammatory bowel disease. Recently, short-chain fatty acids (SCFAs) have been reported to have multifaceted effects to host. However, the effects of SCFAs on wound healing in intestinal epithelial cells are unclear. In the present study, we investigated the effects of acetate, one of the major SCFAs, on the wound healing of murine colonic epithelial cells. METHODS: Young adult mouse colonic epithelial cells were used to determine the effect of acetate using wound healing assay. Mitogen-activated protein kinase and Rho kinase inhibitor were used to elucidate intracellular signal of wound healing treated with acetate. Meanwhile, Rho activation assays were utilized to measure Rho activation levels. To assess in vivo effects, C57B6 mice with dextran sodium sulfate for 7 days were treated with enema administration of acetate for 7 days. Body weight, disease activity index, colon length, and mucosal break ratio in histology were examined. RESULTS: Acetate enhanced wound healing and fluorescence intensity of actin stress fiber compared with control. These effects were canceled with pretreatment of c-Jun N-terminal kinase (JNK) inhibitor or Rho kinase inhibitor. Furthermore, JNK inhibitor reduced the activation of Rho induced by acetate. In the dextran sodium sulfate-induced colitis model, the mice with enema treatment of acetate significantly exhibited recovery. CONCLUSIONS: In this study, we demonstrated that acetate promoted murine colonic epithelial cell wound healing via activation of JNK and Rho signaling pathways. These findings suggested that acetate could have applications as a therapeutic agent for patients with intestinal mucosal damage, such as inflammatory bowel disease.

Mucosa-Associated Microbiota in the Gastrointestinal Tract of Healthy Japanese Subjects.

BACKGROUND: The importance of microbiota infiltrating the gut mucus layer has been reported in the pathogenesis of various gastrointestinal and systemic diseases. However, little is known about the mucosa-associated microbiota (MAM) in healthy subjects. The present study aimed to clarify the characteristics of the gastrointestinal MAM from the oral cavity to the rectum in healthy Japanese subjects. METHODS: Seventeen healthy subjects were enrolled. In this study, 5 mucosa samples from the upper gut (intraoral, mid-esophagus, gastric corpus, gastric antrum, and duodenum) and 7 from the lower gut (ileum, cecum, ascending colon, transverse colon, descending colon, sigmoid colon, and rectum) were collected with a brush under endoscopic examination. MAM profiles of each sample were analyzed by 16S-rRNA V3-V4 gene sequences. RESULTS: Collecting mucosa samples by brushing provided sufficient material for MAM profiling without causing adverse effects. The upper and lower gut MAM profiles differed significantly (p < 0.0001). In the upper and lower gut, the intra- and inter-individual MAM profiles were significantly different (p = 0.0008 and p < 0.0001 respectively). CONCLUSIONS: The MAM profiles of the upper and lower gut were significantly different. The inter-individual differences in MAM were remarkable compared to the intra-individual differences.

Higher Levels of Streptococcus in Upper Gastrointestinal Mucosa Associated with Symptoms in Patients with Functional Dyspepsia.

BACKGROUND: Functional dyspepsia (FD) is associated with poor health-related quality of life. Recent evidence suggests that the main pathogenesis suspect is the gut mucosa-associated microbiota (MAM). However, little is known about the MAM in FD subjects. The aim of this study was to clarify the relationship between upper gastrointestinal symptoms in FD and the characteristics of the gastrointestinal MAM. SUMMARY: Five mucosa samples from the upper gut (intraoral, mid-esophagus, gastric body, gastric antrum, and descending portion of the duodenum) were collected with a brush under endoscopic examination from FD and healthy control subjects. MAM profiles of each sample were analyzed by 16S-rRNA -V3-V4 gene sequences. Questionnaire was used to assess gastrointestinal symptoms in FD. Between FD and healthy control subjects, although the comparison of MAM α-diversity showed no significant differences, the structure of MAM (ß-diversity) was clearly different. Only the phylum Firmicutes was increased in FD compared to healthy control subjects in all sites of the upper gut. At the genus level, Streptococcus was significantly increased in all sites in the upper gut in FD. The relative abundance of Streptococcus was positively correlated with upper gastrointestinal symptoms in each upper gut group. Furthermore, the relative abundance of OTU 90 was positively correlated with upper gastrointestinal symptoms in all sites in the upper gut in FD. Key Messages: Streptococcus is a bacterium strongly correlated with upper gastrointestinal symptoms in FD.

High-Fat Diet Causes Constipation in Mice via Decreasing Colonic Mucus.

BACKGROUND: Constipation is one of the most common gastrointestinal complaints. Although the causes of constipation are varied, dietary habits have a significant influence. Excessive fat intake is suggested as one of the main causes of constipation; however, the exact mechanism is unknown. AIMS: To investigate whether a high-fat diet (HFD) causes constipation in mice and to clarify the underlying mechanism, focusing on the amount of colonic mucus. METHODS: Six-week-old male C57BL/6 mice were randomly divided into two groups: mice fed with HFD and those with normal chow diet (NCD). Fecal weight, water content, total gastrointestinal transit time, and colon transit time were measured to determine whether the mice were constipated. The colonic mucus was evaluated by immunostaining and quantified by spectrometry. Malondialdehyde (MDA) was measured using the thiobarbituric acid (TBA) test as a marker for oxidative stress. RESULTS: Compared to the NCD group, the weight of feces was less in the HFD group. In the functional experiment, the total gastrointestinal transit time and colon transit time were longer in the HFD group. Furthermore, HFD significantly reduced the amount of colonic mucus. In addition, the reduction in colonic mucus caused by surfactant resulted in constipation in the NCD group. CONCLUSIONS: HFD causes constipation with delayed colon transit time possibly via the reduction in colonic mucus in mice.

Effectiveness of including probiotics to Helicobacter pylori eradication therapies.

The eradication rate of Helicobacter pylori (H. pylori) with proton pump inhibitors, amoxicillin, and clarithromycin has reportedly decreased. Some studies have found probiotics to be useful in eradicating H. pylori, but these effects have not been sufficiently investigated. We aimed to elucidate the role of probiotics in eradicating H. pylori infection. Patients in our hospital with H. pylori infection that received standard treatment from January 2015 to December 2016 were retrospectively evaluated (n = 468). They were divided into three groups based on their treatment regime, being either proton pump inhibitors, amoxicillin, or clarithromycin (PPI group), vonoprazan, amoxicillin, or clarithromycin (VPZ group), and proton pump inhibitors, amoxicillin, or clarithromycin/probiotics (Miya-BM®) (PPI + MBM group). We retrospectively evaluated the H. pylori eradication rate and reported side effects. According to intention-to-treat analyses, the eradication rate of H. pylori was significantly higher in the PPI + MBM group (87.1%) than in the PPI group (70.1%). There was no difference in side effects between any of the three groups. In conclusion, Miya-BM® may have an additive effect when included with eradication therapies for H. pylori.

Nutrients and probiotics: current trends in their use to eradicate Helicobacter pylori.

Helicobacter pylori is a well-known bacterium that infects the human gastric mucosa and causes gastric inflammation, ultimately resulting in gastric cancer. To reduce the incidence of gastric cancer, eradication therapy is important. However, the rate of successful eradication gradually decreases due to increased antibiotic resistance to Helicobacter pylori. In order to increase the eradication rate and reduce gastric cancer incidence, food factors or probiotics are expected to play a beneficial role. Although several foods have been reported to inhibit bacterial load and gastric inflammation, further assessment on large population prospective studies in this field is warranted. Several food compounds, including phytochemicals, are reported to suppress the incidence of gastric cancer. Future evaluations should consider differences in geographic factors. Probiotics are effective and safe for use in Helicobacter pylori eradication therapy.