World Journal of Gastroenterology最新文献

{"title":"Platelet activation relieves liver portal hypertension <i>via</i> the lymphatic system though the classical vascular endothelial growth factor receptor 3 signaling pathway.","authors":"Min Chen, Jin-Bo Zhao, Guang-Bo Wu, Zheng-Hao Wu, Gu-Qing Luo, Zhi-Feng Zhao, Chi-Hao Zhang, Jia-Yun Lin, Hong-Jie Li, Xiao-Liang Qi, Hai-Zhong Huo, Abudukadier Tuersun, Qiang Fan, Lei Zheng, Meng Luo","doi":"10.3748/wjg.v31.i10.100194","DOIUrl":"10.3748/wjg.v31.i10.100194","url":null,"abstract":"<p><strong>Background: </strong>Liver cirrhosis and portal hypertension (PHT) can lead to lymphatic abnormalities and coagulation dysfunction. Because lymphangiogenesis may relieve liver cirrhosis and PHT, the present study investigated the gene expression alterations in the lymphatic system and the effectiveness of platelet-mediated lymphangiogenesis in improving liver cirrhosis and PHT.</p><p><strong>Aim: </strong>To investigate the role of lymphangiogenesis in preclinical PHT models.</p><p><strong>Methods: </strong>Immunohistochemistry and transcriptome sequencing of bile duct ligation (BDL) and control lymphatic samples were conducted to reveal the indicated signaling pathways. Functional enrichment analyses were performed on the differentially expressed genes and hub genes. Adenoviral infection of vascular endothelial growth factor C (VEGF-C), platelet-rich plasma (PRP), and VEGF3 receptor (VEGFR) inhibitor MAZ-51 was used as an intervention for the lymphatic system in PHT models. Histology, hemodynamic tests and western blot analyses were performed to demonstrate the effects of lymphatic intervention in PHT patients.</p><p><strong>Results: </strong>Lymphangiogenesis was increased in the BDL rat model. Transcriptome sequencing analysis of the extrahepatic lymphatic system revealed its close association with platelet adherence, aggregation, and activation. The role of PHT in the rat model was investigated by activating (PRP) and inhibiting (MAZ-51) the lymphatic system. PRP promoted lymphangiogenesis, which increased lymphatic drainage, alleviated portal pressure, reduced liver fibrosis, inhibited inflammation, inhibited angiogenesis, and suppressed mesenteric artery remodeling. MAZ-51 reversed the above improvements.</p><p><strong>Conclusion: </strong><i>Via</i> VEGF-C/VEGFR-3, platelets impede fibrosis, angiogenesis, and mesenteric artery remodeling, ultimately alleviating PHT. Thus, platelet intervention is a therapeutic approach for cirrhosis and PHT.</p>","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":"31 10","pages":"100194"},"PeriodicalIF":4.3,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11886527/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143651030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>SEL1L</i>-mediated endoplasmic reticulum associated degradation inhibition suppresses proliferation and migration in Huh7 hepatocellular carcinoma cells.","authors":"Jia-Nan Chen, Li Wang, Yu-Xin He, Xiao-Wei Sun, Long-Jiao Cheng, Ya-Nan Li, Sei Yoshida, Zhong-Yang Shen","doi":"10.3748/wjg.v31.i10.103133","DOIUrl":"10.3748/wjg.v31.i10.103133","url":null,"abstract":"<p><strong>Background: </strong>Proteins play a central role in regulating biological functions, and various pathways regulate their synthesis and secretion. Endoplasmic reticulum-associated protein degradation (ERAD) is crucial for monitoring protein synthesis and processing unfolded or misfolded proteins in actively growing tumor cells. However, the role of the multiple ERAD complexes in liver cancer remains unclear.</p><p><strong>Aim: </strong>To elucidate the effects of <i>SEL1L</i>-mediated ERAD on Huh7 and explore the underlying mechanisms <i>in vivo</i> and <i>in vitro</i>.</p><p><strong>Methods: </strong>Huh7 cells were treated with ERAD inhibitor to identify ERAD's role. Cell counting kit-8, 5-ethynyl-2'-deoxyuridine and colony formation experiments were performed. Apoptosis level and migration ability were assessed using fluorescence activated cell sorting and Transwell assay, respectively. Huh7 <i>SEL1L</i> knockout cell line was established <i>via</i> clustered regularly interspaced short palindromic repeats, proliferation, apoptosis, and migration were assessed through previous experiments. The role of <i>SEL1L in vivo</i> and the downstream target of <i>SEL1L</i> were identified using Xenograft and mass spectrometry, respectively.</p><p><strong>Results: </strong>The ERAD inhibitor suppressed cell proliferation and migration and promoted apoptosis. <i>SEL1L</i>-<i>HRD1</i> significantly influenced Huh7 cell growth. <i>SEL1L</i> knockout suppressed tumor cell proliferation and migration and enhanced apoptosis. Mass spectrometry revealed <i>EXT2</i> is a primary substrate of ERAD. <i>SEL1L</i> knockout significantly increased the protein expression of <i>EXT2</i>. Furthermore, <i>EXT2</i> knockdown partially restored the effect of <i>SEL1L</i> knockout.</p><p><strong>Conclusion: </strong>ERAD inhibition suppressed the proliferation and migration of Huh7 and promoted its apoptosis. <i>EXT2</i> plays an important role and ERAD might be a potential treatment for Huh7 hepatocellular carcinoma.</p>","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":"31 10","pages":"103133"},"PeriodicalIF":4.3,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11886529/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143650433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endoscopic full-thickness resection: A definitive solution for local complete resection of small rectal neuroendocrine neoplasms.","authors":"Xiao-Long Zhang, Yang-Yang Jiang, Ying-Ying Chang, Yu-Li Sun, Ying Zhou, Yao-Hui Wang, Xiao-Tan Dou, Hui-Min Guo, Ting-Sheng Ling","doi":"10.3748/wjg.v31.i10.100444","DOIUrl":"10.3748/wjg.v31.i10.100444","url":null,"abstract":"<p><strong>Background: </strong>Recently, several endoscopic techniques have been used to improve the R0 resection rate of rectal neuroendocrine neoplasms (R-NENs). However, none of these methods can achieve 100% complete resection (CR), particularly in the vertical direction. Endoscopic full-thickness resection (EFTR) has proven to be an effective method for the treatment of submucosal tumors but is seldom utilized in the eradication of R-NENs.</p><p><strong>Aim: </strong>To review cases of R-NENs removed using EFTR and to evaluate the safety and efficacy of this technique.</p><p><strong>Methods: </strong>This retrospective cohort study enrolled 160 patients with pathologically confirmed R-NENs, including 132 who underwent endoscopic submucosal dissection (ESD) and 28 who underwent EFTR. Lesions were categorized as < 1 cm, 1-2 cm, and > 2 cm in size. CR rate, <i>en bloc</i> resection rate, operation time, and complications were evaluated. Subgroup analyses and follow-up were also performed.</p><p><strong>Results: </strong>EFTR achieved 100% CR rates for lesions < 1 cm and 1-2 cm, compared with 67.0% and 50.0%, respectively, in the ESD group. <i>En bloc</i> resection and successful removal of the R-NENs were achieved in all patients. Meanwhile, EFTR showed performance comparable to ESD in terms of operation time, hospitalization cost, and postoperative adverse events, except for a one-day longer hospital stay. We also analyzed the invasion depth of R-NENs based on full-thickness specimens. The data showed that 80% of lesions (< 1 cm) and 85.7% of lesions (1-2 cm) had invaded the SM3 level or deeper at the time of resection. For ESD specimens, 46.6% (< 1 cm) and 89.3% (1-2 cm) of lesions had infiltrated more than 2000 μm beneath the muscularis mucosae.</p><p><strong>Conclusion: </strong>EFTR has shown superior performance in the resection of small R-NENs compared with that of ESD.</p>","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":"31 10","pages":"100444"},"PeriodicalIF":4.3,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11886531/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143651025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial mt12361A>G increased risk of metabolic dysfunction-associated steatotic liver disease among non-diabetes.","authors":"Ming-Ying Lu, Yu-Ju Wei, Chih-Wen Wang, Po-Cheng Liang, Ming-Lun Yeh, Yi-Shan Tsai, Pei-Chien Tsai, Yu-Min Ko, Ching-Chih Lin, Kuan-Yu Chen, Yi-Hung Lin, Tyng-Yuan Jang, Ming-Yen Hsieh, Zu-Yau Lin, Chung-Feng Huang, Jee-Fu Huang, Chia-Yen Dai, Wan-Long Chuang, Ming-Lung Yu","doi":"10.3748/wjg.v31.i10.103716","DOIUrl":"10.3748/wjg.v31.i10.103716","url":null,"abstract":"<p><strong>Background: </strong>Insulin resistance, lipotoxicity, and mitochondrial dysfunction contribute to the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD). Mitochondrial dysfunction impairs oxidative phosphorylation and increases reactive oxygen species production, leading to steatohepatitis and hepatic fibrosis. Artificial intelligence (AI) is a potent tool for disease diagnosis and risk stratification.</p><p><strong>Aim: </strong>To investigate mitochondrial DNA polymorphisms in susceptibility to MASLD and establish an AI model for MASLD screening.</p><p><strong>Methods: </strong>Multiplex polymerase chain reaction was performed to comprehensively genotype 82 mitochondrial DNA variants in the screening dataset (<i>n</i> = 264). The significant mitochondrial single nucleotide polymorphism was validated in an independent cohort (<i>n</i> = 1046) using the Taqman^® allelic discrimination assay. Random forest, eXtreme gradient boosting, Naive Bayes, and logistic regression algorithms were employed to construct an AI model for MASLD.</p><p><strong>Results: </strong>In the screening dataset, only mt12361A>G was significantly associated with MASLD. mt12361A>G showed borderline significance in MASLD patients with 2-3 cardiometabolic traits compared with controls in the validation dataset (<i>P</i> = 0.055). Multivariate regression analysis confirmed that mt12361A>G was an independent risk factor of MASLD [odds ratio (OR) = 2.54, 95% confidence interval (CI): 1.19-5.43, <i>P</i> = 0.016]. The genetic effect of mt12361A>G was significant in the non-diabetic group but not in the diabetic group. mt12361G carriers had a 2.8-fold higher risk than A carriers in the non-diabetic group (OR = 2.80, 95%CI: 1.22-6.41, <i>P</i> = 0.015). By integrating clinical features and mt12361A>G, random forest outperformed other algorithms in detecting MASLD [training area under the receiver operating characteristic curve (AUROC) = 1.000, validation AUROC = 0.876].</p><p><strong>Conclusion: </strong>The mt12361A>G variant increased the severity of MASLD in non-diabetic patients. AI supports the screening and management of MASLD in primary care settings.</p>","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":"31 10","pages":"103716"},"PeriodicalIF":4.3,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11886537/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143651027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current considerations for the management of liver echinococcosis.","authors":"Efstathios T Pavlidis, Ioannis N Galanis, Theodoros E Pavlidis","doi":"10.3748/wjg.v31.i10.103973","DOIUrl":"10.3748/wjg.v31.i10.103973","url":null,"abstract":"<p><p>Echinococcosis or hydatid disease is induced mainly by <i>Echinococcus granulosus</i> and occasionally by <i>Echinococcus multilocularis</i> (alveolaris) and affects the liver predominantly. Hepatic alveolar echinococcosis is similar to carcinoma in appearance, and without treatment, it can lead to death. Diagnosis is based on current imaging modalities. Surgical management is the cornerstone of treatment. Complete removal of the cyst (total pericystectomy or hepatectomy) ensures a permanent cure and should be the first-choice treatment for cystic disease. Cyst evacuation, partial cystectomy, and drainage or omentoplasty, may be alternative choices in difficult cases. Albendazole, mebendazole and praziquantel are options for treating small cysts and preventing recurrence after surgery. Despite the efforts, alveolar echinococcus is not usually amenable to surgical management, except in the early stage, which is less common, and management by albendazole is indicated. However, there are few recent reports of major operations (<i>ex-vivo</i> hepatectomy, autotransplantation and vascular reconstruction) in advanced stages.</p>","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":"31 10","pages":"103973"},"PeriodicalIF":4.3,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11886533/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143650826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment of intermediate-to-advanced unresectable hepatocellular carcinoma is shifting toward a multidisciplinary strategy that includes multiple modalities as needed.","authors":"Ken Sato","doi":"10.3748/wjg.v31.i10.103420","DOIUrl":"10.3748/wjg.v31.i10.103420","url":null,"abstract":"<p><p>In the recent issue of the <i>World Journal of Gastroenterology</i>, Han <i>et al</i> compared the efficacy of and adverse reactions to bevacizumab versus lenvatinib as molecularly targeted agents in combination with interventional therapy and immunotherapy (IMT) to treat intermediate-to-advanced unresectable hepatocellular carcinoma. No significant differences in efficacy or adverse reactions were observed between bevacizumab and lenvatinib. This study is highly promising because in some regions, <i>e.g.</i>, Japan, the combination of molecularly targeted therapy with IMT is fixed because of insurance restrictions, and some molecularly targeted agents cannot be combined with IMT. Further studies using these three modalities are expected to be conducted in the future. Additionally, because advanced radiotherapy modalities have recently been established, the number of combinations continues to increase, and further evidence regarding combination therapy, which is the cornerstone of personalized medicine, needs to be accumulated.</p>","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":"31 10","pages":"103420"},"PeriodicalIF":4.3,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11886538/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143651032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Two treatment methods for hepatocellular carcinoma: Lenvatinib or bevacizumab combined with sintilimab and interventional therapy.","authors":"Fei-Yu Zhao, Xiao-Ming Zhang, Nian-Song Qian","doi":"10.3748/wjg.v31.i10.104429","DOIUrl":"10.3748/wjg.v31.i10.104429","url":null,"abstract":"<p><p>In their study, Han <i>et al</i> compared the efficacy of bevacizumab plus sindilizumab plus interventional therapy with that of lenvatinib plus sindilizumab plus interventional therapy for patients with intermediate and advanced hepatocellular carcinoma. The triple therapy, which integrates interventional therapy, targeted therapy, and immunotherapy, has emerged as a promising research focus in the treatment of liver cancer. Consequently, it is of utmost significance to select an appropriate combination of interventional therapy, targeted therapy, and immunotherapy for patients suffering from intermediate and advanced liver cancer.</p>","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":"31 10","pages":"104429"},"PeriodicalIF":4.3,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11886525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143651033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nab-paclitaxel plus capecitabine as a first-line regimen for advanced biliary tract cancers: Feasible or not feasible?","authors":"Jian-Qiang Chen, Xiang Lan","doi":"10.3748/wjg.v31.i10.100771","DOIUrl":"10.3748/wjg.v31.i10.100771","url":null,"abstract":"<p><p>A clinical trial of nab-paclitaxel plus capecitabine as a first-line treatment for advanced biliary tract cancers was conducted. We analyzed the development of systemic therapy recommended by the National Comprehensive Cancer Network guidelines and the development of nab-paclitaxel combination chemotherapy for advanced biliary tract cancers (BTCs) and concluded that nab-paclitaxel plus capecitabine is a promising first-line regimen for advanced BTCs.</p>","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":"31 10","pages":"100771"},"PeriodicalIF":4.3,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11886530/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143651028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial intelligence in gastroenterology: Ethical and diagnostic challenges in clinical practice.","authors":"Davide Ramoni, Alessandro Scuricini, Federico Carbone, Luca Liberale, Fabrizio Montecucco","doi":"10.3748/wjg.v31.i10.102725","DOIUrl":"10.3748/wjg.v31.i10.102725","url":null,"abstract":"<p><p>This article discusses the manuscript recently published in the <i>World Journal of Gastroenterology</i>, which explores the application of deep learning models in decision-making processes via wireless capsule endoscopy. Integrating artificial intelligence (AI) into gastrointestinal disease diagnosis represents a transformative step toward precision medicine, enhancing real-time accuracy in detecting multi-category lesions at earlier stages, including small bowel lesions and precancerous polyps, ultimately improving patient outcomes. However, the use of AI in clinical settings raises ethical considerations that extend beyond technological potential. Issues of patient privacy, data security, and potential diagnostic biases require careful attention. AI models must prioritize diverse and representative datasets to mitigate inequities and ensure diagnostic accuracy across populations. Furthermore, balancing AI with clinical expertise is crucial, positioning AI as a supportive tool rather than a replacement for physician judgment. Addressing these ethical challenges will support the responsible deployment of AI, through equitable contribution to patient-centered care.</p>","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":"31 10","pages":"102725"},"PeriodicalIF":4.3,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11886536/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143650694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Lactococcus garvieae</i> aggravates cholestatic liver disease by increasing intestinal permeability and enhancing bile acid reabsorption.","authors":"Man Liu, Ying-Lan Ji, Yu-Jie Hu, Ying-Xi Su, Jie Yang, Xiao-Yi Wang, Hong-Yu Chu, Xue Zhang, Shi-Jing Dong, Hui Yang, Yu-Hang Liu, Si-Min Zhou, Li-Ping Guo, Ying Ran, Yan-Ni Li, Jing-Wen Zhao, Zhi-Guang Zhang, Mei-Yu Piao, Lu Zhou","doi":"10.3748/wjg.v31.i10.101014","DOIUrl":"10.3748/wjg.v31.i10.101014","url":null,"abstract":"<p><strong>Background: </strong>Although an association between gut microbiota and cholestatic liver disease (CLD) has been reported, the precise functional roles of these microbes in CLD pathogenesis remain largely unknown.</p><p><strong>Aim: </strong>To explore the function of gut microbes in CLD pathogenesis and the effects of gut microbiota on intestinal barrier and bile acid (BA) metabolism in CLD.</p><p><strong>Methods: </strong>Male C57BL/6J mice were fed a 0.05% 3,5-diethoxycarbonyl-1,4-dihydrocollidine diet for 2 weeks to induce CLD. The sterile liver tissues of mice were then meticulously harvested, and bacteria in homogenates were identified through culture methods. Furthermore, 16S ribosomal DNA sequencing was employed to analyze sterile liver samples collected from eight patients with primary biliary cholangitis (PBC) and three control individuals with hepatic cysts. The functional roles of the identified bacteria in CLD pathogenesis were assessed through microbiota transfer experiments, involving the evaluation of changes in intestinal permeability and BA dynamics.</p><p><strong>Results: </strong><i>Ligilactobacillus murinus</i> (<i>L</i>. <i>murinus</i>) and <i>Lactococcus garvieae</i> (<i>L. garvieae</i>) were isolated from the bacterial culture of livers from CLD mice. <i>L</i>. <i>murinus</i> was prevalently detected in PBC patients and controls, whereas <i>L. garvieae</i> was detected only in patients with PBC but not in controls. Mice inoculated with <i>L. garvieae</i> exhibited increased susceptibility to experimental CLD, with both <i>in vitro</i> and <i>in vivo</i> indicating that <i>L. garvieae</i> disrupted the intestinal barrier function by down-regulating the expression of occludin and zonula occludens-1. Moreover, <i>L. garvieae</i> administration significantly upregulated the expression of the apical sodium-dependent BA transporter in the terminal ileum and increased serum BA levels.</p><p><strong>Conclusion: </strong><i>L. garvieae</i> contributes to excessive BA-induced hepatobiliary injury and liver fibrosis by increasing intestinal permeability and enhancing BA reabsorption.</p>","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":"31 10","pages":"101014"},"PeriodicalIF":4.3,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11886528/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143650222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}