Journal of Gastroenterology最新文献

{"title":"HBV-induced miR-4461 downregulation correlates with elevated fibrinogen alpha chain expression in hepatocellular carcinoma.","authors":"Masatake Kanai, Aiko Sakai, Tomoko Date, Yoshihiko Aoki, Fuminori Mihara, Takashi Kokudo, Fuyuki Inagaki, Nobuyuki Takemura, Norihiro Kokudo, Masaya Sugiyama","doi":"10.1007/s00535-026-02433-1","DOIUrl":"10.1007/s00535-026-02433-1","url":null,"abstract":"<p><strong>Background: </strong>Hepatitis B virus (HBV) infection remains a leading cause of hepatocellular carcinoma (HCC), yet the molecular mechanisms underlying HBV-mediated hepatocarcinogenesis are not fully understood. This study focused on miR-4461, which is encoded within the intronic region of PCBD2 gene, and investigated its role in HBV-derived HCC.</p><p><strong>Methods: </strong>miR-4461 expression was examined in HBV-expressing hepatoma cell lines and in HBV-infected primary human hepatocytes. Functional analysis evaluated the effects of miR-4461 overexpression or inhibition on hepatocyte proliferation. Candidate targets were screened, and fibrinogen alpha chain (FGA) was tested for regulation by miR-4461. Circulating miR-4461 and plasma FGA were measured in patients with chronic viral hepatitis, including those with HBV-related HCC; in the HBV-HCC cohort, FGA was also assessed before and after surgical tumor resection.</p><p><strong>Results: </strong>miR-4461 expression was significantly reduced in HBV-expressing hepatoma cells and HBV-infected primary hepatocytes. Overexpression of miR-4461 inhibited hepatocyte proliferation, whereas its inhibition enhanced proliferation, indicating a tumor-suppressive function. FGA was identified as a downstream target; in hepatoma cells, FGA protein levels were regulated by miR-4461. Clinically, circulating miR-4461 levels were significantly lower in HBV-infected individuals, particularly in those with HBV-related HCC. In contrast, plasma FGA protein levels were markedly elevated in HBV-related HCC and decreased significantly after tumor resection.</p><p><strong>Conclusions: </strong>These findings suggest a novel regulatory axis in HBV-associated HCC involving HBV-induced suppression of miR-4461 and subsequent upregulation of FGA. Both miR-4461 and FGA were associated with disease status, supporting their potential utility as biomarkers or therapeutic targets in HBV-derived HCC.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"1146-1158"},"PeriodicalIF":5.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13407565/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147816129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolite 4-hydroxybenzoic acid, modulated by cigarette smoke exposure, functions as a protective factor in dextran sodium sulfate-induced colitis.","authors":"Masahiro Kitabatake, Tatsuki Nishioka, Atsushi Hara, Kaito Yasuike, Yumiko Nakanishi, Eiji Miyauchi, Noriko Ouji-Sageshima, Hiroshi Ohno, Toshihiro Ito","doi":"10.1007/s00535-026-02484-4","DOIUrl":"10.1007/s00535-026-02484-4","url":null,"abstract":"<p><strong>Background: </strong>Inflammatory bowel disease (IBD) is characterized by chronic gastrointestinal inflammation and comprises ulcerative colitis (UC) and Crohn's disease (CD). Several cohort studies have shown that cigarette smoking (CS) is a risk factor for CD, but it has protective potential for UC. Although CS has been shown to cause different effects on UC and CD, the underlying mechanisms have not been fully determined.</p><p><strong>Methods: </strong>Colitis was induced in CS-exposed mice using two different chemical-induced models: dextran sodium sulfate (DSS) and 2,4,6-trinitrobenzene sulfonic acid (TNBS). We examined pathology of the colon, effector lymphocytes, composition of the microbiota, and intestinal metabolites. We also examined the effect of an intestinal metabolite, 4-hydroxybenzoic acid (4-HBA), on DSS- and TNBS-induced colitis.</p><p><strong>Results: </strong>CS exposure attenuated the pathogenesis of DSS-induced colitis by an increase in regulatory T cells (Tregs) accompanied by an increase in short-chain fatty acid production. By contrast, CS exacerbated TNBS-induced colitis by an increase in effector T cells and the abundance of Enterobacteriaceae, which were correlated with the pathogenesis of IBD. The administration of 4-HBA, which was remarkably increased by CS exposure in the DSS-induced colitis model, suppressed the colonic inflammation accompanying the induction of Tregs and suppression of effector T cells, but exerted no apparent protective effect against TNBS-induced colitis model.</p><p><strong>Conclusion: </strong>CS may regulate colonic inflammation by altering the composition of the microbiota, intestinal metabolites, and immune responses. Additionally, mechanistic findings identified 4-HBA as a potential therapeutic target and provided insights into the development of new therapeutic approaches for UC.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148648676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tofogliflozin alters amino acid metabolism in gut microbiota linked to hepatic transcriptomic signatures in MASLD.","authors":"Kohei Yasuda, Noriho Iida, Yumie Takeshita, Yusuke Masuo, Masao Honda, Toshinari Takamura, Taro Yamashita","doi":"10.1007/s00535-026-02488-0","DOIUrl":"https://doi.org/10.1007/s00535-026-02488-0","url":null,"abstract":"<p><strong>Background: </strong>A deeper understanding of the relationship between dysbiotic gut microbiota and liver tissue-level molecular and histopathological phenotypes in metabolic dysfunction-associated steatotic liver disease (MASLD) remains needed. We aimed to characterize the associations between gut microbial metabolic functions and treatment responses in participants with MASLD.</p><p><strong>Methods: </strong>We performed a prespecified sub-analysis of a randomized controlled trial comparing the sodium-glucose cotransporter 2 inhibitor (SGLT2i) tofogliflozin and the sulfonylurea (SU) glimepiride in participants with MASLD and type 2 diabetes (ClinicalTrials.gov NCT02649465). Fecal whole-genome shotgun metagenomics, liver RNA sequencing, serum profiling, and histopathological assessments were integrated to investigate microbiota-host interactions.</p><p><strong>Results: </strong>Microbial metabolic pathways, rather than taxonomic composition, differed significantly between participants with MASLD and healthy controls. Among the altered microbial pathways, amino acid metabolism emerged as a prominent functional category and was selected for further investigation. Pathways related to amino acid metabolism, particularly phenylalanine metabolism, exhibited opposing patterns: phenylalanine degradation was enriched in MASLD and positively correlated with liver fibrosis scores, whereas phenylalanine biosynthesis inversely correlated with fibrosis severity. Microbial phenylalanine degradation was positively associated with 28 hepatic pathways, including the non-alcoholic fatty liver disease (NAFLD) pathway, in which mitochondria-associated genes were core-enriched. Both SGLT2i and SU treatments improved NAFLD activity scores and altered microbial metabolic pathways without significantly changing microbial species composition. Notably, SGLT2i increased phenylalanine biosynthesis pathways, which were inversely associated with liver fibrosis.</p><p><strong>Conclusions: </strong>Gut microbial amino acid metabolism, particularly phenylalanine metabolism, is closely linked to liver fibrosis and molecular pathways in MASLD. Modulation of microbial metabolic functions may represent a promising therapeutic strategy beyond changes in microbial composition.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148620382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interpreting risk across lean MASLD phenotypes.","authors":"Bin Wei, Huanhuan Li, Xiaorong Wu","doi":"10.1007/s00535-026-02494-2","DOIUrl":"10.1007/s00535-026-02494-2","url":null,"abstract":"","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148630755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world efficacy and safety of avatrombopag in Japanese patients with chronic liver disease and severe thrombocytopenia.","authors":"Yosuke Otsuka, Naoki Morimoto, Satoru Kakizaki, Tadashi Ikegami, Shunji Watanabe, Yuichi Majima, Hirotaka Arai, Takeharu Asano, Yoshihito Uchida, Toshiro Kamoshida, Takeshi Hatanaka, Satoshi Takakusagi, Takeshi Nihei, Atsuko Soeda, Yuichi Yamazaki, Naoyuki Hasegawa, Hidekazu Kurata, Takayoshi Suga, Toshiyuki Tahara, Rie Goka, Mamiko Tsukui, Wataru Ueno, Kouichi Miura, Tomonori Yano, Satoshi Mochida","doi":"10.1007/s00535-026-02489-z","DOIUrl":"https://doi.org/10.1007/s00535-026-02489-z","url":null,"abstract":"<p><strong>Background: </strong>This multicenter retrospective study evaluated the efficacy and safety of avatrombopag (AVA) in Japanese patients with chronic liver disease (CLD) and severe thrombocytopenia in a real-world clinical setting.</p><p><strong>Methods: </strong>The study included CLD patients with platelet counts < 50,000/μL, who received AVA before invasive procedures. Platelet-increasing effect and associated factors were examined, and adverse events were investigated.</p><p><strong>Results: </strong>Sixty-three patients were included, with 10 repeat registrations for different procedure. Thus, the efficacy of AVA was evaluated in 53 unique patients at initial registration, while the comparison based on prior thrombopoietin receptor agonist (TPO-RA) treatment history was conducted in all 63 patients. Patients were divided by baseline platelet count (BPC) into Low BPC (< 40,000/μL; n = 24) and High BPC (≥ 40,000/μL; n = 29) groups. The median platelet counts at baseline and before procedures were 43,000/μL and 75,000/μ, respectively. A platelet increase of ≥ 20,000/μL from baseline was observed in 37 patients (69.8%), and no significant differences were found between the Low BPC and High BPC groups. In addition, a platelet count of ≥ 50,000/μL was achieved in 49 (92.5%) before procedures and 51 (96.2%) avoided platelet transfusions. A multivariate analysis identified body weight > 68 kg as the only significant factor associated with platelet count increase < 20,000/μL. Platelet-increasing effects did not differ by TPO-RA administration history. No adverse events, including portal vein thrombosis or hemorrhagic events, occurred.</p><p><strong>Conclusions: </strong>While interpretation requires caution due to the small sample size, in Japanese real-world practice, AVA was relatively safe and effective in preventing perioperative bleeding and avoiding platelet transfusions.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148620368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical applications of gut microbiome for non-invasive diagnosis of colorectal neoplasia.","authors":"Colin Cui, Haiyun Shi, Yuji Naito, Koji Otani, Francis K L Chan","doi":"10.1007/s00535-026-02487-1","DOIUrl":"https://doi.org/10.1007/s00535-026-02487-1","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is the third most common malignancy and the second leading cause of cancer-related death worldwide. While screening programs have reduced mortality, current stool-based tests such as the faecal immunochemical test (FIT) and tumour marker assays, remain limited in sensitivity for adenoma detection and rely on relatively later-stage biological signals in the carcinogenic process. False positives lead to unnecessary invasive procedures, whilst missed adenomas continue to progress, highlighting the need for alternative strategies. Accumulating evidence implicates the gut microbiome in CRC pathogenesis, which involves tumour-associated dysbiosis and microbial ecosystem shifts. Multinational metagenomic studies have consistently identified reproducible microbial signatures that can serve as biomarkers of disease and may predate the biological signals used in conventional screening. PCR-based microbial markers have emerged as practical tools for clinical application, enabling sensitive and specific detection of adenomas and CRC. A recent microbial panel incorporating Fusobacterium nucleatum, Hungatella hathewayi, Christensenella hongkongensis, and a novel bacterial gene marker m3 from Lachnoclostridium demonstrated improved sensitivity for adenomas whilst maintaining comparable accuracy for CRC. International guidelines have begun to recommend combining microbiome-based assays with FIT into integrated screening programs that target multiple biologic processes across the pathogenesis. Microbiome-based stool testing represents a promising non-invasive approach that improves detection of adenomas in early-stage disease, often missed by FIT alone and could enable more refined risk stratification. Further validation across diverse populations, assessment of cost-effectiveness, and integration into established screening infrastructures will be critical for broad clinical adoption.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148620373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comment on \"Intestinal obstruction impairs the antitumor function of hepatic natural killer cells against colorectal cancer\".","authors":"Zhipeng Fan, Lei Li","doi":"10.1007/s00535-026-02490-6","DOIUrl":"10.1007/s00535-026-02490-6","url":null,"abstract":"","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148603888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of early crystalloid type with mortality and costs in acute pancreatitis: a nationwide cohort study.","authors":"Haruka Okada, Masayasu Horibe, Yusuke Sasabuchi, Fateh Bazerbachi, Tsubasa Sato, Yuichiro Matsuo, Hiroki Matsui, Kiyohide Fushimi, Hideo Yasunaga, Takanori Kanai","doi":"10.1007/s00535-026-02482-6","DOIUrl":"https://doi.org/10.1007/s00535-026-02482-6","url":null,"abstract":"<p><strong>Background: </strong>Early intravenous crystalloid resuscitation is central to acute pancreatitis (AP) management; however, whether normal saline (NS) or balanced Ringer's solutions (RS) are superior for reducing mortality remains unsettled.</p><p><strong>Methods: </strong>Using the Japanese Diagnosis Procedure Combination database (July 2010-March 2022), we identified adults admitted to general medical wards with AP who had a hospital stay longer than 3 days and received sufficient fluid resuscitation within three days of admission. Patients were classified by predominant crystalloid exposure during the first three days (NS vs. RS). Propensity score matching was used to balance measured confounders and compare in-hospital mortality and total hospitalization costs between the two groups.</p><p><strong>Results: </strong>Among 43,247 eligible patients, 1,652 (4.0%) predominantly received NS and 41,595 (96.0%) predominantly received RS. Propensity score matching yielded 1,650 well-balanced pairs. In-hospital mortality was higher with NS than with RS (2.9% vs 1.8%; risk difference, 1.2%; 95% CI, 0.12% to 2.2%). NS was also associated with higher total hospitalization costs (difference, 1,344 USD; 95% CI, 725 to 1,963).</p><p><strong>Conclusions: </strong>In this nationwide cohort of adults with AP admitted to general medical wards, predominant early use of NS was associated with higher in-hospital mortality and higher hospitalization costs compared with RS.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148562127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neoadjuvant and adjuvant treatment for pancreatic ductal adenocarcinoma in patients over 80 years old based on a nationwide clinical database.","authors":"Daisuke Hashimoto, Shinya Hirakawa, Masamichi Mizuma, Hisateru Tachimori, So Yamaki, Takao Itoi, Shinichi Egawa, Yuzo Kodama, Kohei Nakata, Shin Hamada, Ichiro Yasuda, Michiaki Unno, Yoshihiro Kakeji, Ken Shirabe, Sohei Satoi, Atsushi Masamune, Yoshifumi Takeyama","doi":"10.1007/s00535-026-02480-8","DOIUrl":"https://doi.org/10.1007/s00535-026-02480-8","url":null,"abstract":"<p><strong>Background: </strong>The proportion of elderly patients with pancreatic ductal adenocarcinoma (PDAC) is increasing. This study aimed to investigate whether neoadjuvant treatment (NAT) and adjuvant therapy (AT) are effective in PDAC patients over 80 years of age.</p><p><strong>Methods: </strong>Patients over 80 years of age who underwent pancreatectomy for PDAC in 2012-2020 and were recorded in the Japan Society for Gastroenterological Surgery and Japan Pancreas Society databases were included. Propensity score matching (PSM) analysis was performed to determine whether NAT and AT contribute to survival. In patients treated from 2017 onward, resectability status was incorporated into the PSM model.</p><p><strong>Results: </strong>Of the 3438 patients in the study population, the primary resectability-adjusted PSM analysis of NAT among patients treated from 2017 onward compared 274 matched pairs. The MST was 30.5 (95% CI, 26.2-NA) and 29.0 (95% CI, 22.3-38.0) months in the NAT and non-NAT groups, respectively, with no significant difference (p = 0.205 [stratified log-rank]). In a complementary full-cohort PSM analysis, 393 matched pairs were compared; the MST was 32.9 and 30.2 months, respectively, with no significant difference. In a PSM-matched comparison of 1213 patients who received AT versus 1213 patients who did not, MST was longer in the former (30.7 [95% CI, 27.3-33.2] versus 23.7 [95% CI, 21.8-26.1] months, p < 0.001 [stratified log-rank]).</p><p><strong>Conclusion: </strong>NAT did not show a statistically significant survival benefit in PDAC patients aged 80 years or older, however, this finding should be interpreted with caution. In contrast, AT was associated with improved survival.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148470955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter to the Editor to \"Volatomics-based biomarkers for non-invasive diagnosis and monitoring of inflammatory bowel disease\".","authors":"Wenjing Xu, Wenqin Wang, Li Song","doi":"10.1007/s00535-026-02483-5","DOIUrl":"10.1007/s00535-026-02483-5","url":null,"abstract":"","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148471024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}