Gastro hep advances最新文献

{"title":"Helicobacter pylori Exploit Short-Chain Fatty Acids-Induced CAPZA1 Overexpression to Emerge CD44v9-Positive Stemness","authors":"Hitoshi Tsugawa ,&nbsp;Jin Imai ,&nbsp;Eiji Sugiyama ,&nbsp;Chanudporn Sugiyama ,&nbsp;Takashi Ueda ,&nbsp;Miwa Hirai ,&nbsp;Kenichiro Todoroki ,&nbsp;Hidekazu Suzuki","doi":"10.1016/j.gastha.2025.100860","DOIUrl":"10.1016/j.gastha.2025.100860","url":null,"abstract":"<div><h3>Background AND Aims</h3><div>Although <em>Helicobacter pylori</em> infects a large proportion of the global population, only a small subset of the infected individuals develop gastric cancer. The molecular mechanisms underlying the selective progression of gastric carcinogenesis are not fully understood. This study aimed to elucidate these mechanisms by focusing on CD44v9-positive cell generation in <em>H pylori</em>–infected gastric mucosa.</div></div><div><h3>Methods</h3><div>Using <em>H pylori</em> infection models in human gastric adenocarcinoma cells, mice, and mouse-derived gastric organoids, we examined the effects of short-chain fatty acids (SCFAs) on the induction of CD44v9-positive cells using western blotting and immunofluorescence. SCFA concentrations and microbiota compositions were analyzed in gastric juice samples from <em>H pylori</em>–infected patients to evaluate their association with gastric cancer risk.</div></div><div><h3>Results</h3><div>Propionate and butyrate induced capping actin protein of muscle Z-line α subunit 1 (CAPZA1) overexpression via histone deacetylase inhibition. In SCFA-induced CAPZA1-overexpressing cells, the <em>H pylori</em>–derived oncoprotein CagA accumulated due to impaired autophagic degradation, leading to enhanced CD44v9 expression. In the gastric antrum, CD44v9-positive cells undergo CagA-mediated stem cell transformation, whereas a distinct signaling mechanism operates in the gastric corpus. In patients with early gastric cancer, intragastric concentrations of propionate and butyrate are elevated, and the microbiota is enriched with SCFA-producing bacteria.</div></div><div><h3>Conclusion</h3><div>SCFA-induced CAPZA1-overexpressing cells serve as a scaffold niche that supports CagA activity and promotes CD44v9-positive cancer stem-like cells. This study sheds new light on the early molecular events driving <em>H pylori</em>–associated gastric carcinogenesis and may inform future strategies for early detection and intervention.</div></div>","PeriodicalId":73130,"journal":{"name":"Gastro hep advances","volume":"5 3","pages":"Article 100860"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145947951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cover","authors":"","doi":"10.1016/j.gastha.2026.100886","DOIUrl":"10.1016/j.gastha.2026.100886","url":null,"abstract":"","PeriodicalId":73130,"journal":{"name":"Gastro hep advances","volume":"5 2","pages":"Article 100886"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146173390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endoscopic Therapy for Anastomotic Bleeding After Lower Gastrointestinal Surgery in Patients With Crohn’s Disease","authors":"Weiwei Zheng ,&nbsp;Partha Pal ,&nbsp;Yago González-Lama ,&nbsp;Irene González-Partida ,&nbsp;Ravi P. Kiran ,&nbsp;Bo Shen","doi":"10.1016/j.gastha.2025.100835","DOIUrl":"10.1016/j.gastha.2025.100835","url":null,"abstract":"<div><h3>Background and Aims</h3><div>Crohn's disease (CD) patients may experience anastomotic bleeding after lower gastrointestinal surgery, but its endoscopic management remains underexplored. We aimed to analyze the risk factors for anastomotic bleeding and the efficacy of endoscopic treatment.</div></div><div><h3>Methods</h3><div>We retrospectively analyzed clinical characteristics, endoscopic treatments, and outcomes of CD patients with postoperative anastomotic bleeding from January 2021 to May 2025 at multiple centers. Anastomotic bleeding was defined as (i) direct bleeding (melena/hematochezia) or (ii) hemoglobin decrease ≥2 g/dL. Patients were followed up for 1 year, with rebleeding requiring endoscopic reintervention.</div></div><div><h3>Results</h3><div>We included a total of 21 patients with 100% of patients having onsite bleeding controlled with initial endoscopic treatment and 9 patients (42.9%) having rebleeding. There was no statistical difference between the rebleeding group and nonrebleeding group in terms of age, gender, comorbidity, anticoagulation or antiplatelet therapy, clotting disorder, hemoglobin before or after procedure, bleeding type, the Rutgeert’s score, and endoscopic treatment. However, a greater number of patients in the rebleeding group required blood transfusion (88.9% vs 33.3%, <em>P</em> value = .011), and a greater volume of blood transfusion 2.0 (2.0–3.5 units) vs 0.0 (0.0–1.8 units) than those in nonrebleeding group (<em>P</em> value = .013). None of the 21 patients had no endoscopy-associated complications.</div></div><div><h3>Conclusion</h3><div>Endoscopic therapy appears to be safe and effective for the majority of CD patients with anastomotic bleeding following bowel surgery. The requirement for blood transfusion at the inception, in conjunction with a high volume of blood transfusion appear to be high risk factors for rebleeding.</div></div>","PeriodicalId":73130,"journal":{"name":"Gastro hep advances","volume":"5 4","pages":"Article 100835"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147410005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ten Years in a Pediatric Center: Detecting Esophageal Pathology and Symptoms in Aerodigestive Patients","authors":"Kaitlin Ballenger ,&nbsp;Anupama Kewalramani ,&nbsp;Lauren Bernard ,&nbsp;Kathryn Driscoll ,&nbsp;Jaylyn Waddell ,&nbsp;Anayansi Lasso-Pirot ,&nbsp;Jennifer Hong","doi":"10.1016/j.gastha.2025.100879","DOIUrl":"10.1016/j.gastha.2025.100879","url":null,"abstract":"<div><h3>Background and Aims</h3><div>Eosinophilic esophagitis (EoE) and gastroesophageal reflux disease (GERD) share overlapping gastrointestinal and pulmonary manifestations, often complicating timely diagnosis. Aerodigestive evaluation integrates endoscopic and bronchoscopic approaches to better characterize these patients, yet data on esophageal pathology frequency and associated symptomatology in pediatric patients remain limited.</div></div><div><h3>Methods</h3><div>We performed a retrospective cross-sectional chart review of pediatric patients (ages 1–18) who underwent esophagogastroduodenoscopy with biopsy and bronchoscopy with bronchoalveolar lavage (BAL) between 2013 and 2023 at a tertiary care center. Patients were classified as having EoE (≥15 eosinophils/high power field [hpf]), GERD-associated esophagitis (&lt;15 eosinophils/hpf or reactive changes), or normal esophageal biopsies. Demographics, medication use, gastrointestinal and pulmonary symptoms, and BAL cytology were compared among groups.</div></div><div><h3>Results</h3><div>Of 126 included patients, 21 (16.7%) had EoE, 31 (24.6%) had GERD-associated esophagitis, and 74 (58.7%) had normal esophageal biopsies. Gastrointestinal complaints were more frequent in patients with normal biopsies (77%) than GERD-associated esophagitis (17%, <em>P</em> = .05) or EoE (57%, <em>P</em> = .007), with abdominal pain significantly higher in normal biopsies compared to GERD-associated esophagitis (23% vs 6.5%, <em>P</em> &lt; .04). Pulmonary symptoms were common across groups, with snoring more prevalent in EoE (19% vs 5.4%, <em>P</em> &lt; .05). BAL revealed elevated eosinophils in EoE compared to GERD-associated esophagitis and normal esophagus (8.1% vs 1.0% and 1.6%, respectively), while GERD-associated esophagitis showed higher mean total white blood cell counts.</div></div><div><h3>Conclusion</h3><div>Gastrointestinal and pulmonary symptoms did not reliably predict esophageal pathology, with significant overlap observed across groups. The presence of histologic esophagitis despite minimal gastrointestinal complaints underscores limitations of symptom-guided evaluation alone. Aerodigestive assessment offers diagnostic value for pediatric patients with refractory respiratory symptoms and facilitates recognition of esophageal disease.</div></div>","PeriodicalId":73130,"journal":{"name":"Gastro hep advances","volume":"5 3","pages":"Article 100879"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146183757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss of Nonhematopoietic Osteopontin Weakens the Intestinal Barrier and Alters the Microbiome and Metabolome in Mice","authors":"Takehiro Hirano ,&nbsp;Kohei Wagatsuma ,&nbsp;Yuta Shimomori ,&nbsp;Kotaro Akita ,&nbsp;Tomoya Nakamura ,&nbsp;Tsukasa Yamakawa ,&nbsp;Yoshihiro Yokoyama ,&nbsp;Hiroki Kurumi ,&nbsp;Keisuke Ishigami ,&nbsp;Kanna Nagaishi ,&nbsp;Hiroshi Nakase","doi":"10.1016/j.gastha.2026.100883","DOIUrl":"10.1016/j.gastha.2026.100883","url":null,"abstract":"<div><h3>Background and Aims</h3><div>Inflammatory bowel disease (IBD) is characterized by intestinal barrier disruption and dysregulated interactions between host immunity and gut microbiota. Osteopontin (OPN) is considered a proinflammatory mediator in IBD, but nonhematopoietic cell-derived OPN may exert barrier-protective functions. This study aimed to determine the effects of OPN in a murine model of acute colitis.</div></div><div><h3>Methods</h3><div>We examined wild-type and OPN knockout mice under steady-state conditions and in dextran sulfate sodium–induced colitis, including bone marrow chimeras to distinguish the effects of hematopoietic and nonhematopoietic OPN.</div></div><div><h3>Results</h3><div>Overt colitis did not occur under steady-state conditions. Compared with wild-type mice, OPN knockout mice exhibited crypt elongation, goblet cell hyperplasia, and increased epithelial proliferation. Gene expression analysis revealed reduced interleukin (IL)-22, IL-23, and IL-13 levels alongside increased interferon-γ, IL-1β, and IL-17A levels. 16S rRNA sequencing revealed increased alpha diversity, expansion of <em>Akkermansia</em> and <em>Prevotellaceae</em>, and reduced <em>Lactobacillus</em> abundance. Functional prediction identified enrichment of microbial sulfur metabolism pathways, and metabolomic analysis demonstrated increased L-proline and L-(−)-fucose levels and reduced β-sitosterol levels. These shifts indicate enhanced mucinolytic activity and altered energy metabolism, consistent with a latent “preinflammatory state.” Bone marrow chimera experiments demonstrated that OPN deficiency in the recipients reproduced changes in the microbiota composition and lipocalin-2 expression at the steady state and conferred heightened susceptibility to dextran sulfate sodium–induced acute colitis, irrespective of donor genotype.</div></div><div><h3>Conclusion</h3><div>These findings indicate that nonhematopoietic cell-derived “guardian-type” OPN preserves barrier integrity, sustains IL-22/IL-23 production, and maintains microbiota–metabolome balance, whereas its loss induces a preinflammatory state that predisposes to acute mucosal injury. These findings provide a conceptual basis for stage- and source-specific therapeutic strategies in IBD.</div></div>","PeriodicalId":73130,"journal":{"name":"Gastro hep advances","volume":"5 4","pages":"Article 100883"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147328308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cholate Clearance: Improving the Assessment of Liver Health Compared to Current Liver Tests","authors":"James R. Burton Jr.,&nbsp;Edward Mena,&nbsp;Bhaktasharan Patel","doi":"10.1016/j.gastha.2025.100814","DOIUrl":"10.1016/j.gastha.2025.100814","url":null,"abstract":"","PeriodicalId":73130,"journal":{"name":"Gastro hep advances","volume":"5 2","pages":"Article 100814"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145555171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Cystic Fibrosis Transmembrane Conductance Regulator Modulating Therapies on Liver Transplant Outcomes","authors":"Sara Naimimohasses ,&nbsp;Ankit Ray ,&nbsp;Eunice Tan ,&nbsp;Asher Wiggins ,&nbsp;Bima J. Hasjim ,&nbsp;Shiyi Chen ,&nbsp;Mamatha Bhat","doi":"10.1016/j.gastha.2025.100810","DOIUrl":"10.1016/j.gastha.2025.100810","url":null,"abstract":"<div><h3>Background and Aims</h3><div>Up to 40% of patients with cystic fibrosis (CF) develop CF-related liver disease (CFrLD), which can progress to the point of requiring liver transplantation (LT). Advances in CF transmembrane conductance regulator (CFTR) modulator therapies, especially triple therapy modulators, have significantly improved pulmonary outcomes, but their impact on LT for CFrLD remains unclear.</div></div><div><h3>Methods</h3><div>Using data from the Scientific Registry of Transplant Recipients in 2000-2023, we analyzed trends in LT waitlisting for CFrLD pre- and post-U.S. Food and Drug Administration (FDA) approval of CFTR modulators: ivacaftor (January 31, 2012; single therapy), ivacaftor-lumacaftor (July 2, 2015; dual therapy), and ivacaftor-tezacaftor-elexacaftor (October 21, 2019; triple therapy). We compared the waitlist characteristics and post-LT outcomes of pre- and post-FDA approval eras.</div></div><div><h3>Results</h3><div>Of 258,090 patients waitlisted for LT, 551 (0.2%) had CFrLD. The proportion of CFrLD patients on the LT waitlist decreased after FDA approval of triple CFTR modulators (0.23% to 0.14%; <em>P</em> &lt; .0004). Patients waitlisted after FDA approval of single and dual CFTR modulators were, on average, older (17.4 vs 20.6 years; <em>P</em> &lt; .001 and 18.0 vs 20.8 years; <em>P</em> = .004). Median model for end-stage liver disease-sodium scores were higher among individuals waitlisted following the approval of dual (9 [6–14] vs 10 [8–15], <em>P</em> &lt; .013) and triple (9 [6–14] vs 12.5 [8–17], <em>P</em> &lt; .003) CFTR modulators. There were no significant differences in post-LT survival pre- and post-FDA approval of single, dual, or triple CFTR therapy.</div></div><div><h3>Conclusion</h3><div>These findings suggest that CFTR modulators may mitigate CFrLD complications and delay the need for waitlisting as physicians await the patient’s response to therapy and reassess the need for LT.</div></div>","PeriodicalId":73130,"journal":{"name":"Gastro hep advances","volume":"5 2","pages":"Article 100810"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145555170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neonatal and Pregnancy Outcomes in Pregnant Adults With Pediatric-Onset Crohn’s Disease","authors":"Supraja Swamy ,&nbsp;Jean-Paul Achkar ,&nbsp;Stacey Ehrenberg ,&nbsp;Alex Zajichek ,&nbsp;Alex Milinovich ,&nbsp;Ravi S. Shah ,&nbsp;Jessica Barry ,&nbsp;Sandra C. Kim ,&nbsp;Jacob A. Kurowski","doi":"10.1016/j.gastha.2026.100959","DOIUrl":"10.1016/j.gastha.2026.100959","url":null,"abstract":"<div><h3>Background and Aims</h3><div>Low birth weight (BW) and preterm birth are recognized complications in women with active Crohn’s disease (CD). However, there is limited information on pregnancy and neonatal outcomes in patients diagnosed during childhood and adolescence. This study aims to evaluate the relationship between maternal age at CD diagnosis and pregnancy and neonatal outcomes.</div></div><div><h3>Methods</h3><div>We conducted a retrospective, cross-sectional study of women with CD who delivered between 2012 and 2023. Gestational age (GA) at delivery and (BW) were analyzed as coprimary outcomes.</div></div><div><h3>Results</h3><div>A total of 262 births from 179 mothers were included, with 105 (40.1%) births from women diagnosed with CD before age 18. No significant differences were observed in GA at delivery between groups. There was a significantly higher rate of neonates born small for GA to mothers with adult-onset CD compared with pediatric-onset CD (15.9% vs 3.8%, <em>P</em> = .002). The odds of delivering a small-for-GA infant decreased by 21% for every 10% increase in the proportion of a woman’s life spent living with CD (95% confidence interval [CI]: 0.65–0.96). A CD flare during pregnancy resulted in a 10.9% reduction in BW percentile at delivery (95% CI: −20.05 to −1.64). Antitumor necrosis factor therapy at the time of conception was associated with an 8.7% increase in BW percentiles (95% CI: 1.13–16.27).</div></div><div><h3>Conclusion</h3><div>Neonates born to women with pediatric-onset CD have excellent outcomes including GA and BW percentiles at delivery. Longer disease duration and antitumor necrosis factor therapy were positively associated with improved BW percentiles, while disease activity had a negative impact. These findings suggest that disease control has a more significant impact on neonatal outcomes than age of onset or disease duration.</div></div>","PeriodicalId":73130,"journal":{"name":"Gastro hep advances","volume":"5 6","pages":"Article 100959"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147859483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A 360-Degree Alimentary Limb Volvulus After Roux-en-Y Gastric Bypass","authors":"Christian Mouawad,&nbsp;Abdessalem Ghedira,&nbsp;Nehad Dager","doi":"10.1016/j.gastha.2026.100962","DOIUrl":"10.1016/j.gastha.2026.100962","url":null,"abstract":"","PeriodicalId":73130,"journal":{"name":"Gastro hep advances","volume":"5 6","pages":"Article 100962"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147952630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Outcomes of Difficult-to-Treat Ulcerative Colitis: Impact of Primary Nonresponse vs Secondary Loss of Response to Prior Therapies","authors":"Terry Lou ,&nbsp;Yuchen Qi ,&nbsp;Melissa Kirkpatrick ,&nbsp;Brigid S. Boland ,&nbsp;Siddharth Singh","doi":"10.1016/j.gastha.2026.100949","DOIUrl":"10.1016/j.gastha.2026.100949","url":null,"abstract":"","PeriodicalId":73130,"journal":{"name":"Gastro hep advances","volume":"5 6","pages":"Article 100949"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147952631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}