Introduction: Epidemiological evidence regarding the association between equol and precancerous colorectal lesions, including adenomas, sessile serrated lesions, and traditional serrated adenomas, remains unclear. Moreover, since equol production status depends on the composition of the gut microbiota and varies widely among individuals, evaluation based on plasma levels is essential. In this study, we evaluated the association between plasma equol levels and precancerous colorectal lesions. Methods: This cross-sectional study included residents aged 40-79 years in Izu Oshima, Japan. Blood samples were collected at study registration prior to colonoscopy under fasting conditions. In 2024, plasma equol levels were analyzed by gas chromatography-mass spectrometry, and individuals above the measurement quantification limit were classified as equol producers. Colonoscopy was performed for screening, and lesions were assessed based on endoscopic and pathological findings. Odds ratios (ORs) and their 95% confidence intervals (CIs) for precancerous lesions were calculated. Results: Of the 993 participants analyzed, 509 had precancerous colorectal lesions, while 484 served as controls. No significant association was observed between equol production status and the presence of precancerous colorectal lesions (OR: 1.04, 95% CI: 0.77-1.40). Although not statistically significant, an inverse trend was suggested in advanced lesions, defined as advanced adenomas or SSLs with dysplasia (OR: 0.63, 95% CI: 0.34-1.18). Conclusion: This study did not provide significant evidence of an association between equol production status and the presence of precancerous colorectal lesions. Future prospective cohort studies and detailed analysis of intestinal microbiota are needed to clarify the effects of equol on colorectal carcinogenesis.

Introduction: Eosinophilic enteritis (EoN) remains underrecognized because of nonspecific symptoms and difficulty obtaining deep small intestinal biopsies. We evaluated the diagnostic utility of double balloon enteroscopy (DBE)-guided multisite biopsy and explored tissue and blood eosinophil thresholds distinguishing EoN from non-EoN conditions. Methods: This single-center retrospective cohort included consecutive patients who underwent DBE with small intestinal biopsies (January 2021–December 2024). Biopsies were obtained from up to six predefined segments (duodenum, upper/lower jejunum, upper/lower ileum, terminal ileum). EoN diagnosis required abdominal pain and/or diarrhea, exclusion of competing diagnoses, and small intestinal biopsy-proven eosinophilic infiltration. Peripheral eosinophil percentage and computed tomography (CT) findings were recorded. The primary outcome was the extent of small intestinal eosinophil infiltration in patients with EoN. Secondary outcomes were the peripheral blood eosinophil count, clinical background, and exploratory comparisons with non-EoN cases. Results: Eighteen patients were included (5 EoN, 13 non-EoN). CT showed small intestinal wall edema in 3 patients with EoN. Peripheral eosinophil proportion was significantly higher in EoN (median, 15.2% vs. 1.9%; p < 0.01). Across 83 biopsy specimens (25 EoN, 58 non-EoN), patient-level peak eosinophil counts were greater in EoN (median, 77/HPF [22–213] vs. 23/HPF [12–111]; p < 0.001). All patients with EoN had at least one segment with ≥50 eosinophils per high-power field, while two with non-EoN reached this threshold. No DBE-related serious adverse events occurred. Conclusion: EoN exhibits significantly greater eosinophil infiltration than non-EoN. DBE-guided multisite biopsy enables accurate recognition of EoN. Prospective multicenter studies are needed to refine site-specific thresholds and standardize HPF reporting.

Mirikizumab (MIR), a selective IL-23p19 inhibitor, has shown efficacy in clinical trials for ulcerative colitis (UC). However, real-world data, especially on long-term outcomes and in treatment-experienced populations, remain limited. We conducted a multicenter retrospective cohort study involving 85 patients with moderate-to-severe UC who initiated MIR between July 2023 and December 2024 across 12 Japanese centers. Co-primary endpoints were clinical remission (Simple Clinical Colitis Activity Index [SCCAI] ≤2 and with no rectal bleeding) at weeks 12 and 52. Secondary outcomes included corticosteroid (CS)-free remission, CRP normalization, treatment persistence, and safety. Clinical remission was achieved in 62.4% at week 12 and 55.3% at week 52. CS-free remission rates were identical to overall remission at both time points. MIR maintained effectiveness regardless of prior exposure to biologics or JAK inhibitors. Early clinical response at week 4 independently predicted week 52 remission, while steroid dependence was a predictor at week 12. Among patients receiving extended induction, 27.3% of initial nonresponders achieved remission by week 24. Treatment was generally well tolerated, with 17.6% experiencing adverse events and 9.4% discontinuing due to these events. No serious infections or hospitalizations occurred. MIR demonstrated durable effectiveness and a favorable safety profile over 52 weeks in a real-world UC population, including those with prior treatment failures. These findings support MIR as a viable long-term therapeutic option in routine clinical practice.

Introduction: Reliable closure of mucosal/full-thickness defects after endoscopic treatment is crucial to prevent complications. Although various techniques have been clinically introduced, a direct comparison of these techniques has not been conducted. Thus, the present ex vivo study aimed to evaluate the closure strength of these methods. Methods: Using a porcine stomach, 4 × 2.5-cm mucosal and full-thickness defects were prepared. Each closure was performed for three specimens. For the mucosal defects, the following methods were performed in the mucosal (group M) and muscular-mediated mucosal (group MM) closures: simple clipping (clip-M), loop-assisted closure (loop-M), line-assisted closure (line-M), and endoscopic hand suturing (EHS-M); clip-MM, line-MM, and EHS-MM. For the full-thickness defects, a single-layered closure (group F) was performed by loop-assisted closure (loop-F), line-assisted clip closure (line-F), and EHS (EHS-F). The maximum tension (N) was measured using a mechanical traction device by mechanically pulling both ends of the specimen. Results: In the closure of mucosal defects, among the techniques in group M, EHS-M (11.32 ± 2.1 N) demonstrated the highest strength as compared to the other three methods. For group MM, EHS-MM (13.1 ± 5.3 N) showed the highest strength, significantly outperforming clip-MM (p = 0.03). Among the full-thickness defect closure methods, EHS-F (9.5 ± 0.73 N) had the significantly highest strength among the three methods. Conclusions: Our ex vivo data showed that EHS has superior closure strength in both mucosal and full-thickness defects. Surgery-oriented endoscopic closure appears to be a reliable method for artificially created intraluminal defects.

Introduction: Risankizumab (RZB), an IL-23p19 monoclonal antibody, has demonstrated clinical efficacy in Crohn’s disease (CD), yet evidence regarding its effectiveness for deep small-intestinal lesions remains scarce. These lesions are often underdiagnosed due to limited accessibility and subtle clinical presentation. Methods: We retrospectively analyzed 32 patients with moderate-to-severe CD who underwent total small-intestinal evaluation by double-balloon endoscopy (DBE) both before and 8–14 months after RZB initiation in clinical practice. Endoscopic disease activity was assessed using the modified Simple Endoscopic Score for Crohn’s Disease (mSES-CD). Clinical response (Crohn’s Disease Activity Index [CDAI]), biomarker changes (C-reactive protein, leucine-rich alpha-2 glycoprotein), and endoscopic outcomes were evaluated. Results: Mean mSES-CD significantly decreased from 14.3 to 8.2 (p < 0.001), indicating substantial mucosal improvement, particularly in the jejunum and deep ileum. Endoscopic remission (mSES-CD <2) was achieved in 13.3% of patients. Clinical remission (CDAI <150) occurred in 80% at week 12 and was sustained in 56% at 1 year. Significant biomarker improvements were observed. No progression of strictures was seen during follow-up. Conclusion: This study confirms the therapeutic efficacy of RZB for deep small-intestinal involvement in CD based on comprehensive DBE assessment. The results support the clinical utility of RZB in patients with refractory small-intestinal lesions, highlighting its potential to maintain 1 year disease control when ongoing mucosal inflammation is a concern. These findings underscore the importance of deep enteroscopic evaluation to optimize therapeutic strategies.

Introduction: The efficacy of electroacupuncture (EA) treatment in alleviating visceral hypersensitivity with irritable bowel syndrome (IBS) has been established. Abnormal bile acid metabolism and farnesoid X receptor (FXR) expression are recognized as potential contributors to visceral hypersensitivity in IBS. This study as a preclinical study of IBS visceral hypersensitivity explored the potential of EA to reduce visceral hypersensitivity in rats with IBS by improving bile acid metabolism and FXR expression. Methods: Heterotypic intermittent stress (HIS) for 9 days was used to induce visceral hypersensitivity in constipation-predominant irritable bowel syndrome (IBS-C). EA/sham EA bilateral ST36 and LR3 acupoints began on the 5th day of HIS. Electromyography of the abdominal external oblique muscle and calcitonin gene-related peptide were used to assess colonic hypersensitivity. Colonoscopy and histopathological examination were used to evaluate pathological changes in the colon. Bile acid composition was analyzed using high-performance liquid chromatography-mass spectrometry, while FXR expression in colon tissue was quantified through immunofluorescence and Western blot. Results: HIS induced visceral hypersensitivity in IBS-C rats. EA not only regulated bile acid levels in the feces of IBS-C rats, but also had a downregulatory effect on the overexpression of FXR in the colon tissue of rats with IBS-C. The therapeutic effects were better than those of the sham EA. EA treatment alleviated visceral hypersensitivity in the colon of IBS-C rats. Conclusion: Our data suggested that EA normalized colonic bile acid signaling and FXR protein expression in an IBS-C rat model, offering a mechanistic hypothesis for future clinical evaluation.

Background: Emerging evidence highlights the gut microbiota as a key contributor to the pathophysiology of irritable bowel syndrome (IBS), acting through complex interactions with intestinal motility, immune function, epithelial barrier integrity, and the gut-brain axis. This narrative review summarizes current knowledge regarding the roles of the gut microbiota and their metabolites in IBS. Summary: We discuss alterations in the gut microbiota in IBS, with particular emphasis on changes in short-chain fatty acid production, bile acid metabolism, serotonin signaling, and gas handling. Special attention is given to microbial metabolites as mediators of visceral hypersensitivity, intestinal permeability, and neuromodulation within the microbiota-gut-brain axis. Major alterations in the gut microbiota of IBS are characterized by a reduction in Bacteroidetes, Bifidobacteria, and Faecalibacterium, accompanied by an increase in Firmicutes. We explain the importance of butyrate metabolism in colonic epithelial cells for maintaining the anaerobic environment of the gut. In addition, we review the impact of diet-microbiota interactions, including FODMAP restriction, resistant starch intake, and protein fermentation, on symptom generation and microbial stability. Key Message: Although accumulating evidence supports a link between gut dysbiosis and IBS, establishing causal relationships remains challenging due to disease heterogeneity and dietary influences. Future large-scale, well-phenotyped, multi-omics studies integrating microbiota, metabolomic, and host factors are required to elucidate underlying mechanisms and to guide personalized therapeutic strategies for IBS.

Introduction: High-risk chronic atrophic gastritis (CAG; OLGA/OLGIM Ⅲ-Ⅳ) carries significant gastric cancer (GC) risk yet lacks reliable gastric stem cell (GSC)-based biomarkers. We evaluated GSC markers LGR5 (proliferative) and TFF2 (protective) for risk stratification. Methods: TCGA/GEO bioinformatics analysis preceded immunohistochemical validation in 60 clinical samples. Protein co-expression (Wnt/β-catenin, Ki67, Bax) was assessed. Diagnostic/prognostic power was tested via ROC and Kaplan-Meier analyses. Functional networks were deciphered through GO/KEGG enrichment. Results: High-risk CAG and GC tissues showed LGR5 upregulation and TFF2 downregulation (p < 0.001). IHC confirmed these patterns, with concurrent Wnt activation (β-catenin↑, cyclin D1↑) and proliferation-apoptosis imbalance (Ki67↑, Bax↓). TFF2 outperformed LGR5 in diagnosing high-risk CAG (AUC: 0.842 vs. 0.681). Poor GC prognosis correlated with high LGR5/low TFF2 (p < 0.05). Co-expression networks linked LGR5 to metabolic genes (CPS1, ADH6) and TFF2 to mucosal defense (GKN1, PGC). Conclusion: The coordinated assessment of LGR5 and TFF2 offers a promising approach to identifying high-risk CAG. This biomarker pair captures a homeostatic imbalance in GSCs linked to Wnt/β-catenin signaling, establishing a novel molecular framework for early detection and future targeted strategies.

Introduction: Achalasia is an esophageal motility disorder that significantly impairs quality of life. Recently, peroral endoscopic myotomy has yielded satisfactory treatment outcomes. Although the current gold standard is esophageal high-resolution manometry (HRM), early endoscopic detection is essential for accurate diagnosis. Dilatation of the esophageal lumen during endoscopy is subjective and has not been fully evaluated. We focused on the extramural compression of the vertebrae in the esophagus, which may reflect dilatation of the esophageal lumen, named the endoscopic vertebrae sign (EVS), and examined the possibility of the EVS as a novel endoscopic finding of achalasia. Methods: Forty-three patients were diagnosed with achalasia using HRM between July 2013 and November 2022. Five who underwent surgical treatment and one for whom esophagogram was unavailable were excluded, resulting in 37 patients in the achalasia group. Among those who underwent comprehensive medical checkups and esophagogastroduodenoscopy screening at our hospital during the same period, all age- and sex-matched individuals were randomly extracted and 74 were set as controls. The rates of EVS, endoscopic esophageal dilatation at the endoscopist’s discretion, and number of visible vertebrae in a single endoscopic view were retrospectively analyzed. Results: In the achalasia group, the proportion with EVS was 86.5%, with endoscopic esophageal dilatation at the endoscopist’s discretion 76%, and the number of visible vertebrae in patients with EVS was 3.2 ± 0.9. These findings differed significantly in controls: 9.5%, 0%, and 1.4 ± 0.4, respectively (p < 0.001). Conclusion: EVS may be one of the endoscopic findings associated with esophageal dilatation and suggestive of achalasia.

Background: Gastric cancer (GC) has a significant impact in Asia. Delay in diagnosis and treatment leads to increased mortality and morbidity. The detection of gastric intestinal metaplasia (GIM) has the potential to be an early sign of GC, but there are controversies. Differences in GC and pre-cancerous lesions between Asians and non-Asians have also contributed to this controversy. Summary: GIM is a risk factor for developing GC in Asian adults, with more recent meta-analyses demonstrating a 3–4 risk in such patients. Certain GIM subtypes are more likely to develop GC, with Asian patients appearing to have more severe, diffuse, and high-risk subtypes of GIM compared to non-Asians. As a result, most international guidelines recommend endoscopic surveillance in adults with GIM, but this review article suggests it should be targeted towards those with high-risk features. This review also highlights other factors, apart from gastric histology, which are relevant in the development of GC. Factors such as Helicobacter pylori virulence, molecular and genetic mechanisms, gut microbiota, specific dietary components, and social habits as risk factors for GC are discussed. Key Messages: GIM is a risk factor for GC in the Asian population. Surveillance in a targeted population is beneficial.