Frontiers in gastroenterology (Lausanne, Switzerland)最新文献

{"title":"The menopause-obesity axis in MASH progression: from estrogen decline to liver fibrosis.","authors":"Anastasia Ntikoudi, Eugenia Vlachou","doi":"10.3389/fgstr.2026.1889458","DOIUrl":"10.3389/fgstr.2026.1889458","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) have emerged as major global health challenges, particularly among individuals with obesity and metabolic dysfunction. Menopause represents a critical hormonal transition characterized by estrogen deficiency, visceral adiposity, insulin resistance, and chronic low-grade inflammation, all of which may accelerate MASH progression and hepatic fibrosis in women. This narrative review summarizes current evidence regarding the menopause-obesity axis in MASH progression, focusing on molecular mechanisms, histopathological alterations, diagnostic biomarkers, imaging modalities, and emerging therapeutic strategies. Estrogen deficiency contributes to metabolic dysregulation through impaired insulin signaling, increased visceral adiposity, lipotoxicity, oxidative stress, and adipose tissue inflammation, thereby promoting hepatic steatosis and progression toward fibrosis. Histopathological progression is characterized by steatosis, hepatocyte ballooning, chronic inflammation, and extracellular matrix deposition. Non-invasive diagnostic approaches, including serum biomarkers, transient elastography, controlled attenuation parameter (CAP), and magnetic resonance imaging proton density fat fraction (MRI-PDFF), have improved disease detection and risk stratification. Lifestyle modification and sustained weight reduction remain the cornerstone of management, while emerging pharmacologic therapies such as glucagon-like peptide-1 receptor agonists, tirzepatide, and resmetirom demonstrate promising metabolic and hepatic benefits. Hormone-based and anti-fibrotic therapies may offer additional therapeutic potential in postmenopausal women with obesity-associated MASH. Collectively, the menopause-obesity axis appears to play a central role in hepatic injury and fibrosis progression through interconnected hormonal, metabolic, and inflammatory pathways. Improved understanding of sex-specific mechanisms may facilitate the development of personalized diagnostic and therapeutic approaches for postmenopausal women with MASLD and MASH.</p>","PeriodicalId":73085,"journal":{"name":"Frontiers in gastroenterology (Lausanne, Switzerland)","volume":"5 ","pages":"1889458"},"PeriodicalIF":0.0,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13519902/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148842260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut microecology in critical illness: mechanisms, biomarkers, and therapeutic strategies - a critical appraisal.","authors":"Liang Tian, Shanshan Xu, Xueping Xie, Man Wang, Lina Huang","doi":"10.3389/fgstr.2026.1902608","DOIUrl":"https://doi.org/10.3389/fgstr.2026.1902608","url":null,"abstract":"<p><p>Critical illness is associated with a predictable ecological collapse of the gut microbiome. Within 48 hours of ICU admission, three convergent selective pressures-luminal oxygen enrichment from mucosal inflammation, nitrate provision by iNOS, and antibiotic-mediated niche clearance-drive a phase transition from obligate-anaerobe-dominated communities to pathogen-dominated monocultures, compromising barrier integrity and immune homeostasis. Multi-omics integration recasts this as a cross-kingdom phenomenon encompassing fungi, bacteriophages, and the metabolite networks linking them to host immunity. Whether this collapse directly causes organ dysfunction or merely marks disease severity remains the central unresolved question. This critical review examines evidence across six domains: the healthy microbiota as an ecological benchmark; patterns and temporal dynamics of ICU dysbiosis; molecular mechanisms across four gut-organ axes; clinical consequences including sepsis, nosocomial infection, acute gastrointestinal injury, and multiple organ dysfunction syndrome (MODS); biomarkers and machine-learning predictive models; and therapeutic strategies evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. Only early enteral nutrition (GRADE: HIGH) and antimicrobial stewardship (GRADE: MODERATE-HIGH) have Phase III evidence supporting routine ICU use. The repeated failures of probiotic trials reflect design limitations-lack of patient stratification, strain mismatch, and soft endpoints-though biological efficacy limitations cannot be excluded. We conclude that ICU dysbiosis is best understood as ecosystem collapse driven by convergent selective pressures, not random taxonomic disturbance. Therapeutic strategies should target functional outputs-SCFAs, bile acids, indole derivatives-rather than species composition. The resilient minority (15-20% of patients who maintain diversity) holds keys to prevention science. A clinically actionable platform requires three components: rapid ecological risk assessment, endotype classification, and mortality-powered randomized controlled trials targeting functional restoration.</p>","PeriodicalId":73085,"journal":{"name":"Frontiers in gastroenterology (Lausanne, Switzerland)","volume":"5 ","pages":"1902608"},"PeriodicalIF":0.0,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13487743/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148801749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic drug monitoring with non-anti-TNF advanced therapies in inflammatory bowel disease: current and evolving paradigms.","authors":"Faris Chater, Thomas D Butler, Jimmy K Limdi","doi":"10.3389/fgstr.2026.1860608","DOIUrl":"https://doi.org/10.3389/fgstr.2026.1860608","url":null,"abstract":"<p><p>Inflammatory bowel diseases, encompassing Crohn's disease and ulcerative colitis, are chronic inflammatory disorders of the gastrointestinal tract. The recent expansion in advanced therapy options has not dramatically altered the ceiling of treatment efficacy. Therapeutic drug monitoring (TDM) of the serum drug levels and anti-drug antibodies has the potential to optimise treatment efficacy through dose adjustment. TDM has shown benefit with purine analogues and anti-tumour necrosis factor (TNF) therapy. Less is known about the role of TDM in non-anti-TNF advanced therapies. This review summarises the current evidence base for TDM in non-anti-TNF advanced therapies.</p>","PeriodicalId":73085,"journal":{"name":"Frontiers in gastroenterology (Lausanne, Switzerland)","volume":"5 ","pages":"1860608"},"PeriodicalIF":0.0,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13483069/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148801791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endoscopic submucosal dissection for a large (exceeding 3 cm) exophytic gastric schwannoma with 24-hour intragastric retention: a case report and brief literature review.","authors":"Rong Xie, Weiwei Zhang, YanningI Mao, Yi Qin, Jiaxu Wang, Qi Luo, Linhua Teng, Jiawen Liu","doi":"10.3389/fgstr.2025.1703551","DOIUrl":"https://doi.org/10.3389/fgstr.2025.1703551","url":null,"abstract":"<p><strong>Background: </strong>The clinical role of endoscopic resection in the treatment of exophytic gastric schwannomas measuring ≥3 cm remains controversial owing to technical difficulties and a paucity of evidence.</p><p><strong>Case presentation: </strong>A 58-year-old female patient was admitted for treatment after a gastric mass was discovered during routine physical examination. Endoscopic ultrasonography (EUS) revealed a well-demarcated, hypoechoic submucosal tumor measuring 40.9×32.3 mm. The patient subsequently underwent endoscopic submucosal dissection (ESD) under general anesthesia. Histopathological analysis confirmed the diagnosis of gastric schwannoma, with immunohistochemical staining showing strong S-100 protein positivity. The patient had an uneventful recovery with no procedure-related complications, and there has been no evidence of recurrence to date.</p><p><strong>Conclusion: </strong>While this single-case experience indicates the technical feasibility of ESD for gastric schwannomas >3 cm, larger-scale prospective studies are required to establish its role in clinical practice.</p>","PeriodicalId":73085,"journal":{"name":"Frontiers in gastroenterology (Lausanne, Switzerland)","volume":"4 ","pages":"1703551"},"PeriodicalIF":0.0,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13472825/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148761873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of the traditional Chinese medicine formulation BL-1 for the treatment of low anterior resection syndrome: study protocol for a double-blind, randomized, placebo-controlled trial.","authors":"Jun Zhao, Jianxia Dong, Yu Zhang, Shi-Yu Tang, Qing Li, Qiangqi Cai, Xuemei Zhang, Lie Yang, Lin Zhu","doi":"10.3389/fgstr.2026.1767318","DOIUrl":"https://doi.org/10.3389/fgstr.2026.1767318","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;Low anterior resection syndrome (LARS), a prevalent sequela following rectal cancer surgery, poses a substantial burden on patients' quality of life (QOL), daily functioning, and psychological well-being, and its management remains an unmet clinical need due to the absence of specific therapeutic agents. Although traditional Chinese medicine (TCM) shows promise in supporting postoperative gastrointestinal recovery, high-quality evidence for its application in LARS is lacking. This trial is designed to assess the efficacy and safety of the investigational TCM formulation BL-1 in patients with LARS.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods/design: &lt;/strong&gt;The study will be conducted as a randomized, double-blind, placebo-controlled trial, comprising a 4-week intervention phase and a subsequent 2-week follow-up period. A total of 234 patients with LARS, aged 18 to 75 years, are planned to be enrolled in this study. Eligible participants will be randomized to receive either the BL-1 group or placebo group in a 1:1 ratio. Participants in the experimental group will receive BL-1 formulation, whereas those in the placebo group will receive an indistinguishable BL-1 placebo. The primary outcome measure is the change in LARS score from baseline to week 4. Secondary outcome measures encompass: (a) stool frequency and consistency (assessed via the Bristol Stool Scale); (b) severity of fecal incontinence (evaluated using the Wexner Anal Incontinence Scale); (c) QOL, measured with the European Organization for Research and Treatment of Cancer QOL questionnaire and the Karnofsky Performance Status score; and (d) other patient-reported outcomes. Safety will be monitored continuously throughout the treatment, with assessments including the incidence of adverse events and laboratory abnormalities.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Discussion: &lt;/strong&gt;BL-1 is the compound prescription of eleven traditional Chinese medicinal materials: Bupleuri Herba, Ginseng Radix et Rhizoma, Astragali Radix, Atractylodis Macrocephalae Rhizoma, Cimicifugae Rhizoma, Mume Fructus, and Aconiti Lateralis Radix Praeparata (patent number ZL 2024 1 1479878.8). In recent years, BL-1 has been applied to treat digestive system diseases, particularly defecation disorders, and may offer potential benefits for adults with LARS. The absence of robust clinical evidence has prompted the design of this randomized, double-blind, placebo-controlled trial to rigorously evaluate its therapeutic efficacy and safety. This trial is expected to yield critical data that will inform the clinical use of BL-1 formulation in the management of LARS.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Ethics and dissemination: &lt;/strong&gt;Ethical approval for this study was obtained from the Ethics Committee of West China Hospital, Sichuan University (Approval ID: 20241218). All participants must provide written informed consent before randomization. Subsequently, the trial results will be submitted for publication in a peer-reviewed academic journal.&lt;/p&gt;&lt;p&gt;","PeriodicalId":73085,"journal":{"name":"Frontiers in gastroenterology (Lausanne, Switzerland)","volume":"5 ","pages":"1767318"},"PeriodicalIF":0.0,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13467974/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148762940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimised mesalazine therapy reduces ulcerative colitis recurrence across the mild-to-moderate disease spectrum: the IMPACT study.","authors":"Bolette Christophersen, John Fullarton, Rachel West","doi":"10.3389/fgstr.2026.1874051","DOIUrl":"10.3389/fgstr.2026.1874051","url":null,"abstract":"<p><strong>Introduction: </strong>Optimised oral mesalazine therapy (4 or 4.8 g/day depending on the formulation) has been associated with better outcomes than lower doses in mild-to-moderate ulcerative colitis (UC). The aim of this <i>post-hoc</i> analysis of the IMPACT study was to provide a greater understanding of the influence of disease severity on the outcomes in patients with mild-to-moderate UC receiving oral mesalazine.</p><p><strong>Methods: </strong>IMPACT was a Dutch, phase 4, non-interventional, observational, 12-month prospective study that enrolled 151 adult patients with mild-to-moderate UC who received oral prolonged-release mesalazine <i>de novo</i> or had a dose escalation for an active episode (NCT02261636). The current analysis compared the outcomes in patients receiving mesalazine 4 g/day <i>versus</i> 2-3 g/day.</p><p><strong>Results: </strong>Of 147 patients (median age = 46 years, 47.6% women), 139 (94.6%) received 4 g/day, mostly as prolonged-release mesalazine granules (74.2%). Recurrence was significantly reduced for patients on 4 g/day <i>versus</i> 2-3 g/day (26.6% <i>vs.</i> 62.5%, <i>p</i> = 0.03). There was a trend towards a longer disease-free interval for those on the optimised dose over the 12-month period (mean = 16.8 <i>vs.</i> 12.8 months, <i>p</i> = 0.49). Time to recurrence was similar (<i>p</i> = 0.241) for patients with milder [Ulcerative Colitis Disease Activity Index (UCDAI) scores ≤3] <i>versus</i> more moderately active disease (scores ≥4), with a significantly higher rate of combined oral plus topical therapy in the latter (23.2% <i>vs.</i> 46.1%, <i>p</i> = 0.004). Patients' preferred formulation was granules (68.0%) given once daily (78.7%), with good adherence to all formulations (≥8.5/10, high = 10) irrespective of regimen (<i>p</i> = 0.873).</p><p><strong>Discussion: </strong>Optimised mesalazine treatment improved the clinical outcomes in patients across the spectrum of mild-to-moderate UC.</p>","PeriodicalId":73085,"journal":{"name":"Frontiers in gastroenterology (Lausanne, Switzerland)","volume":"5 ","pages":"1874051"},"PeriodicalIF":0.0,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13453671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148708605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Congenital hepatic fibrosis in an adult female combined with Von Meyenburg complex and autosomal dominant polycystic kidney disease: a case report.","authors":"Xinrui Ren, Yu Cui, Jiayi Song, Yiwen Tang, Xiaoying Xie, Wanchun Zhu, Zhuo Yu, Lingying Huang, Yueqiu Gao","doi":"10.3389/fgstr.2026.1876545","DOIUrl":"10.3389/fgstr.2026.1876545","url":null,"abstract":"<p><strong>Background: </strong>Congenital hepatic fibrosis (CHF) is a rare disease associated with the polycystic kidney gene, and the initial symptoms are often associated with portal hypertension, such as splenomegaly and esophageal varices. While the basic clinical features and pathogenesis of isolated CHF have been thoroughly studied, patients frequently present variable combined phenotypes including autosomal dominant polycystic kidney disease (ADPKD) and Von Meyenburg complex (VMC). The pathogenic mechanisms driving these composite phenotypes require further exploration.</p><p><strong>Methods and results: </strong>We report a case of an adult female patient who was admitted due to unexplained upper gastrointestinal bleeding. Upon admission, the patient was diagnosed with congenital hepatic fibrosis in conjunction with VMC and ADPKD, based on findings from liver puncture biopsy, exome sequencing (ES), biochemical tests, and imaging examinations.</p><p><strong>Conclusions: </strong>The PKD1 gene is the causative gene for this patient's CHF combined with VMC and ADPKD.</p>","PeriodicalId":73085,"journal":{"name":"Frontiers in gastroenterology (Lausanne, Switzerland)","volume":"5 ","pages":"1876545"},"PeriodicalIF":0.0,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13447153/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148690346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The new era of MASH pharmacotherapy: a comprehensive review of FDA-approved and emerging agents.","authors":"Abeer Qasim, Rayan Alataa, Fnu Veena, Elona Shehi","doi":"10.3389/fgstr.2026.1850915","DOIUrl":"10.3389/fgstr.2026.1850915","url":null,"abstract":"<p><strong>Background: </strong>Metabolic dysfunction-associated steatohepatitis (MASH), formerly nonalcoholic steatohepatitis (NASH), is a progressive liver disease and a leading cause of cirrhosis and liver-related mortality worldwide, affecting approximately 3%-5% of the global adult population and up to 30%-40% of individuals with type 2 diabetes mellitus (T2DM) or those attending dedicated diabetes and endocrine centers. For decades, treatment was limited to lifestyle interventions. The years 2024 and 2025 marked a paradigm shift with the first-ever FDA approvals of pharmacologic agents for MASH.</p><p><strong>Scope: </strong>This comprehensive narrative review synthesizes the evidence for newly approved and emerging pharmacotherapies for MASH, addressing the mechanisms of action, pivotal clinical trial data, efficacy, safety profiles, and place in therapy for resmetirom and semaglutide. It also discusses key agents including pioglitazone, saroglitazar, and vitamin E, and evaluates the non-invasive testing (NIT) toolkit-including FIB-4, VCTE, shear wave elastography, MRE, and ELF-in the context of a structured, risk-stratified clinical algorithm.</p><p><strong>Findings: </strong>Resmetirom (Rezdiffra), a THR-β agonist, achieved MASH resolution in 26%-30% versus 10% placebo and fibrosis improvement in 24%-26% versus 14% placebo at 52 weeks in the MAESTRO-NASH trial. Semaglutide 2.4 mg (Wegovy) demonstrated a 28.7% delta over placebo in MASH resolution in the ESSENCE trial. Pioglitazone has additional evidence for reducing the FIB-4 index in real-world studies. Saroglitazar, a PPAR-α/γ dual agonist approved in India, has shown significant reductions in ALT, liver fat, and metabolic parameters in Phase 2 studies and is advancing to Phase 2b. Shear wave elastography is a clinically important alternative to VCTE for fibrosis staging, particularly in patients with obesity, and offers value in resolving discordant FIB-4/VCTE results.</p><p><strong>Conclusion: </strong>The approval of resmetirom and semaglutide marks a new era in MASH management. A risk-stratified algorithmic approach using NITs guides patient selection, with liver biopsy reserved for specific clinical scenarios. The therapeutic landscape is rapidly evolving, with saroglitazar and combination approaches representing key frontiers.</p>","PeriodicalId":73085,"journal":{"name":"Frontiers in gastroenterology (Lausanne, Switzerland)","volume":"5 ","pages":"1850915"},"PeriodicalIF":0.0,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13441763/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148686956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A real-world assessment of healthcare resource utilization following IBS-Smart ^® and Trio-Smart ^® testing in patients with suspected irritable bowel syndrome.","authors":"Leonard Weinstock, William B Salt, Lynn Cherry, Christopher Tyson, Raf Magar","doi":"10.3389/fgstr.2026.1681818","DOIUrl":"10.3389/fgstr.2026.1681818","url":null,"abstract":"<p><strong>Background: </strong>IBS is a disorder of gut-brain interaction that is diagnosed positively but still requires a focused differential diagnosis and limited rule-out testing. IBS-Smart and Trio-Smart are commercially available serologic and breath tests that may alter diagnostic sequencing in clinical practice.</p><p><strong>Objective: </strong>To evaluate whether receipt of IBS-Smart and/or Trio-Smart was associated with differences in diagnostic resource utilization, captured diagnostic cost, chart-level diagnostic persistence, and medication use compared with contemporaneous control patients who did not receive these tests.</p><p><strong>Methods: </strong>This retrospective two-center cohort study included 219 adults with symptoms suggestive of IBS. Patients were grouped as IBS-Smart only (n=48), Trio-Smart only (n=43), both tests (n=11), or controls receiving neither test (n=117). Costs reflected a payer-proxy perspective in 2022 US dollars and included captured diagnostic tests and gastroenterology office visits. The archived study used propensity matching and an exploratory generalized linear model (GLM) for total diagnostic cost.</p><p><strong>Results: </strong>Colonoscopy rates were 50.0% in the IBS-Smart-only cohort, 53.5% in the Trio-Smart-only cohort, 27.3% in the combined-testing cohort, and 60.7% in controls; upper endoscopy rates were 31.3%, 41.9%, 0.0%, and 48.7%, respectively. Among patients first seen in 2018 or later, mean total captured diagnostic plus office-visit cost per patient per month was $366.85 for IBS-Smart only, $382.87 for Trio-Smart only, $361.83 for both tests, and $960.39 for controls. In the archived propensity-matched GLM, IBS-Smart testing was associated with lower total diagnostic cost (coefficient -0.22; P = 0.050), corresponding to an estimated incremental savings of $526 per patient. Stable chart-level diagnosis was observed in 79.2% of IBS-Smart-only patients, 90.7% of Trio-Smart-only patients, 72.7% of patients after IBS-Smart in the combined cohort, 90.9% after Trio-Smart in the combined cohort, and 25.6% of controls. Medication counts decreased descriptively in several tested subgroups at one year; drug-class-level aggregation could not be reconstructed reliably from the archived medication file and is therefore not overstated.</p><p><strong>Conclusions: </strong>In this observational study, receipt of IBS-Smart and/or Trio-Smart was associated with lower captured resource utilization and greater chart-level diagnostic persistence than standard care alone. These findings should be interpreted as real-world associations rather than causal proof and do not replace Rome IV-based evaluation, alarm-feature triage, or guideline-recommended rule-out testing.</p>","PeriodicalId":73085,"journal":{"name":"Frontiers in gastroenterology (Lausanne, Switzerland)","volume":"5 ","pages":"1681818"},"PeriodicalIF":0.0,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13441705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148686888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SR9009 regulates macrophage polarization via the NR1D1/NF-κB axis to ameliorate obesity-associated ulcerative colitis.","authors":"Zhixue Zheng, Xuan Cai, Yaqi Liu, Jingtao Bi","doi":"10.3389/fgstr.2026.1762028","DOIUrl":"10.3389/fgstr.2026.1762028","url":null,"abstract":"<p><strong>Objective: </strong>The incidence of ulcerative colitis (UC) and obesity has risen in recent years, potentially linked through metabolic dysregulation and chronic inflammation. The nuclear receptor NR1D1 is pivotal in regulating circadian rhythms and plays a significant role in inflammation and metabolism. This study investigates the therapeutic effects and mechanisms of the NR1D1 agonist SR9009 on obesity-related UC.</p><p><strong>Methods: </strong>We established a mouse model of obesity-induced UC utilizing a high-fat diet alongside dextran sulfate sodium (DSS). 32 male C57BL/6 mice were divided into four groups: control (DZ), high-fat diet (GZ), obesity associated UC model group (UC), and SR9009 intervention group (JD), with eight mice each. We evaluated body weight, blood lipids, colonic tissue alterations, IL-1β, IL-18, macrophage polarization, and NR1D1 expression levels.</p><p><strong>Results: </strong>Mice in the UC group demonstrated significantly elevated body weight, spleen index, TG, CHOL and inflammatory markers (<i>P</i> < 0.01). Pathological scores of colonic tissues increased markedly (<i>P</i> < 0.001), with a rise in M1 macrophages (CD68⁺) and a decline in M2 macrophages (CD206⁺) (<i>P</i> < 0.001). NR1D1 expression was notably downregulated (P<0.01). Post-SR9009 intervention, the JD group showed significantly reduced serum TG and CHOL levels (<i>P</i> = 0.001, 0.011), IL-1β and IL-18 (P<0.001), improved colonic pathology (<i>P</i> < 0.001), a decrease in M1 macrophages, an increase in M2 macrophages, and an enhanced M1/M2 ratio (P<0.001).</p><p><strong>Conclusion: </strong>SR9009 mitigates intestinal inflammation in obesity associated UC by activating NR1D1, potentially modulating NF-κB-related signaling, and modulating macrophage polarization (suppressing M1 and enhancing M2). These findings propose a novel strategy for targeting NR1D1 in the treatment of obesity-related ulcerative colitis.</p>","PeriodicalId":73085,"journal":{"name":"Frontiers in gastroenterology (Lausanne, Switzerland)","volume":"5 ","pages":"1762028"},"PeriodicalIF":0.0,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13441730/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148686990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}