World Journal of Gastroenterology最新文献

{"title":"Arachidonate 15-lipoxygenase: A promising therapeutic target for alleviating inflammation in acute pancreatitis.","authors":"Duygu Kirkik, Sevgi Kalkanli Tas","doi":"10.3748/wjg.v31.i15.102752","DOIUrl":"https://doi.org/10.3748/wjg.v31.i15.102752","url":null,"abstract":"<p><p>This article discusses the significant findings from the study on the transfection of arachidonate 15-lipoxygenase (ALOX15) and its therapeutic potential in managing acute pancreatitis (AP). The research highlights the role of ALOX15 in attenuating inflammatory responses, apoptosis, and autophagy in a cerulein-induced AP murine model. By using a recombinant lentiviral vector for efficient gene delivery, the study provides compelling evidence for the protective effects of ALOX15 transfection on pancreatic tissue. The authors demonstrate that ALOX15 reduces the expression of key inflammatory markers like interleukin-β and tumor necrosis factor α while promoting apoptosis through caspase-3 activation. Furthermore, the modulation of autophagy and structural preservation of pancreatic acinar cells suggest that ALOX15 could be a promising therapeutic target for AP. The implications of these findings are discussed, emphasizing the potential for future clinical translation and further research to explore the molecular mechanisms and therapeutic applications of ALOX15 in inflammatory diseases.</p>","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":"31 15","pages":"102752"},"PeriodicalIF":4.3,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12038556/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144049573","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":"Rethinking carnitine palmitoyltransferase II and liver stem cells in metabolic dysfunction-associated fatty liver disease-related hepatocellular carcinoma.","authors":"Hong Cai, Chun-Hui Yang, Peng Gao","doi":"10.3748/wjg.v31.i15.104528","DOIUrl":"https://doi.org/10.3748/wjg.v31.i15.104528","url":null,"abstract":"<p><p>This article discusses a recent study by Wang <i>et al</i> that sheds light on the metabolic and immunological mechanisms driving the progression of metabolic dysfunction-associated fatty liver disease (MAFLD) to hepatocellular carcinoma (HCC). The study highlights the role of mitochondrial carnitine palmitoyltransferase II (CPT II) inactivity, which activates liver cancer stem cells marked by cluster of differentiation 44 (CD44) and CD24 expression, promoting HCC development. Using dynamic mouse models and clinical samples, Wang <i>et al</i> identified CPT II downregulation, mitochondrial membrane potential alterations, and reduced intrahepatic CD4⁺ T cell as key drivers of disease progression. The findings link these changes to steroid biosynthesis and p53 signaling, contributing to T-cell dysfunction and immunosuppression. This article emphasizes the relevance of these results in understanding MAFLD pathogenesis and discusses potential therapeutic strategies targeting CPT II activity, mitochondrial function, and immune surveillance to prevent or mitigate HCC development in advanced MAFLD.</p>","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":"31 15","pages":"104528"},"PeriodicalIF":4.3,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12038545/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144030341","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":"Strain- and sex-dependent variability in hepatic microcirculation and liver function in mice.","authors":"Bing Wang, Yuan Li, Qin Ouyang, Meng-Ting Xu, Ying-Yu Wang, Sun-Jing Fu, Wei-Qi Liu, Xue-Ting Liu, Hao Ling, Xu Zhang, Rui-Juan Xiu, Ming-Ming Liu","doi":"10.3748/wjg.v31.i15.101058","DOIUrl":"https://doi.org/10.3748/wjg.v31.i15.101058","url":null,"abstract":"<p><strong>Background: </strong>The integrity and functionality of the hepatic microcirculation are essential for maintaining liver health, which is influenced by sex and genetic background. Understanding these variations is crucial for addressing disparities in liver disease outcomes.</p><p><strong>Aim: </strong>To investigate the sexual dimorphism and genetic heterogeneity of liver microcirculatory function in mice.</p><p><strong>Methods: </strong>We assessed hepatic microhemodynamics in BALB/c, C57BL/6J, and KM mouse strains using laser Doppler flowmetry and wavelet analysis. We analyzed the serum levels of alanine transaminase, glutamic acid aminotransferase, total bile acid, total protein, alkaline phosphatase, and glucose. Histological and immunohistochemical staining were employed to quantify microvascular density and the expression levels of cluster of differentiation (CD) 31, and estrogen receptor α, and β. Statistical analyses, including the Mantel test and Pearson correlation, were conducted to determine the relationships among hepatic function, microcirculation, and marcocirculation between different sexes and across genetic backgrounds.</p><p><strong>Results: </strong>We identified sex-based disparities in hepatic microhemodynamics across all strains, with males exhibiting higher microvascular perfusion and erythrocyte concentration, but lower blood velocity. Strain-specific differences were evident, particularly in the endothelial oscillatory characteristics of the erythrocyte concentration. No sex-dependent differences in estrogen receptor expression were observed, while significant variations in CD31 expression and microvascular density were observed. The correlations highlighted relationships between hepatic microhemodynamics and liver function indicators.</p><p><strong>Conclusion: </strong>Our findings indicate the influence of genetic and sex differences on hepatic microcirculation and liver function, highlighting the necessity of incorporating both genetic background and sex into hepatic physiology studies and potential liver disease management strategies.</p>","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":"31 15","pages":"101058"},"PeriodicalIF":4.3,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12038547/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144050406","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":"Predictive models and clinical manifestations of intrapulmonary vascular dilatation and hepatopulmonary syndrome in patients with cirrhosis: Prospective comparative study.","authors":"Zhi-Peng Wu, Ying-Fei Wang, Feng-Wei Shi, Wen-Hui Cao, Jie Sun, Liu Yang, Fang-Ping Ding, Cai-Xia Hu, Wei-Wei Kang, Jing Han, Rong-Hui Yang, Qing-Kun Song, Jia-Wei Jin, Hong-Bo Shi, Ying-Min Ma","doi":"10.3748/wjg.v31.i15.105720","DOIUrl":"https://doi.org/10.3748/wjg.v31.i15.105720","url":null,"abstract":"<p><strong>Background: </strong>Patients with cirrhosis with hepatopulmonary syndrome (HPS) have a poorer prognosis. The disease has a subtle onset, symptoms are easily masked, clinical attention is insufficient, and misdiagnosis rates are high.</p><p><strong>Aim: </strong>To compare the clinical characteristics of patients with cirrhosis, cirrhosis combined with intrapulmonary vascular dilatation (IPVD), and HPS, and to establish predictive models for IPVD and HPS.</p><p><strong>Methods: </strong>Patients with cirrhosis were prospectively screened at a liver-specialized university teaching hospital. Clinical information and blood samples were collected, and biomarker levels in blood samples were measured. Patients with cirrhosis were divided into three groups: Those with pure cirrhosis, those with combined IPVD, and those with HPS based on contrast-enhanced transthoracic echocardiography results and the pulmonary alveolar-arterial oxygen gradient values. Univariate logistic regression and Least Absolute Shrinkage and Selection Operator (LASSO) regression methods were utilized to identify risk factors for IPVD and HPS, and nomograms were constructed to predict IPVD and HPS.</p><p><strong>Results: </strong>A total of 320 patients were analyzed, with 101 diagnosed with IPVD, of whom 54 were diagnosed with HPS. There were statistically significant differences in clinical parameters among these three groups of patients. Among the tested biomarkers, sphingosine 1 phosphate, angiopoietin-2, and platelet-derived growth factor BB were significantly associated with IPVD and HPS in patients with cirrhosis. Following LASSO logistic regression screening, prediction models for IPVD and HPS were established. The area under the receiver operating characteristic curve for IPVD prediction was 0.792 (95% confidence interval [CI]: 0.737-0.847), and for HPS prediction was 0.891 (95%CI: 0.848-0.934).</p><p><strong>Conclusion: </strong>This study systematically compared the clinical characteristics of patients with cirrhosis, IPVD, and HPS, and constructed predictive models for IPVD and HPS based on clinical parameters and laboratory indicators. These models showed good predictive value for IPVD and HPS in patients with cirrhosis. They can assist clinicians in the early prognosis assessment of patients with cirrhosis, ultimately benefiting the patients.</p>","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":"31 15","pages":"105720"},"PeriodicalIF":4.3,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12038555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144036774","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":"Management of hepatic encephalopathy following transjugular intrahepatic portosystemic shunts: Current strategies and future directions.","authors":"Ying Li, Yu-Tong Wu, Hao Wu","doi":"10.3748/wjg.v31.i15.103512","DOIUrl":"https://doi.org/10.3748/wjg.v31.i15.103512","url":null,"abstract":"<p><p>Transjugular intrahepatic portosystemic shunts (TIPSs) are generally used for the management of complications of portal hypertension in patients with decompensated cirrhosis. However, hepatic encephalopathy (HE), which impairs neuropsychiatric function and motor control, remains the primary adverse effect of TIPS, limiting its utility. Prompt prevention and treatment of post-TIPS HE are critical, as they are strongly associated with readmission rates and poor quality of life. This review focuses on the main pathophysiological mechanisms underlying post-TIPS HE, explores advanced biomarkers and predictive tools, and discusses current management strategies and future directions to prevent or reverse HE following TIPS. These strategies include preoperative patient assessment, individualized shunt diameter optimization, spontaneous portosystemic shunt embolization during the TIPS procedure, postoperative preventive and therapeutic measures such as nutrition management, medical therapy, fecal microbiota transplantation, and stent reduction.</p>","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":"31 15","pages":"103512"},"PeriodicalIF":4.3,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12038546/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144026457","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":"Delaying liver aging: Analysis of structural and functional alterations.","authors":"Yu-Qin Yao, Qiong-Yue Cao, Zheng Li","doi":"10.3748/wjg.v31.i15.103773","DOIUrl":"https://doi.org/10.3748/wjg.v31.i15.103773","url":null,"abstract":"<p><p>This article is based on a recent bibliometric analysis of research progress on liver aging. The liver is notable for its extraordinary ability to rejuvenate, thereby safeguarding and maintaining the organism's integrity. With advancing age, there is a noteworthy reduction in both the liver's size and blood circulation. Furthermore, the wide range of physiological alterations driven on by aging may foster the development of illnesses. Previous studies indicate that liver aging is linked to impaired lipid metabolism and abnormal gene expression associated with chronic inflammation. Factors such as mitochondrial dysfunction and telomere shortening accumulate, which may result in increased hepatic steatosis, which impacts liver regeneration, metabolism, and other functions. Knowing the structural and functional changes could help elderly adults delay liver aging. Increasing public awareness of anti-aging interventions is essential. Besides the use of dietary supplements, alterations in lifestyle, including changes in dietary habits and physical exercise routines, are the most efficacious means to decelerate the aging process of the liver. This article highlights recent advances in the mechanism research of liver aging and summarizes the promising intervention options to delay liver aging for preventing related diseases.</p>","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":"31 15","pages":"103773"},"PeriodicalIF":4.3,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12038549/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144049831","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":"Rhapontin activates nuclear factor erythroid 2-related factor 2 to ameliorate 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced gastrointestinal dysfunction in Parkinson's disease mice.","authors":"Xin-Yu Wang, Fang Liu, Qi-Tong Wang, Shu-Zhu Li, Yu-Zhao Ye, Tao Chen, Ben-Chi Cai","doi":"10.3748/wjg.v31.i15.104875","DOIUrl":"https://doi.org/10.3748/wjg.v31.i15.104875","url":null,"abstract":"<p><strong>Background: </strong>Parkinson's disease (PD)-a progressive neurodegenerative disorder-is characterized by motor and gastrointestinal dysfunction. The exploration of novel therapeutic strategies for PD is vital.</p><p><strong>Aim: </strong>To investigate the potential mechanism of action of rhapontin-a natural compound with known antioxidant and anti-inflammatory properties-in the context of PD.</p><p><strong>Methods: </strong>Network pharmacology was used to predict the targets and mechanisms of action of rhapontin in PD. Behavioral tests and tyrosine hydroxylase immunofluorescence analysis were used to assess the effect of rhapontin on symptoms and pathology in MPTP-induced mice. Interleukin (IL)-6, IL-1β, tumor necrosis factor (TNF)-α, and IL-10 levels in tissues were measured using an enzyme-linked immunosorbent assay (ELISA). Additionally, nuclear factor erythroid 2-related factor 2 (NRF2) activation was confirmed using western blotting.</p><p><strong>Results: </strong>NRF2 was predicted to be the key transcription factor underlying the therapeutic effects of rhapontin in PD, and its anti-PD action may be associated with its anti-inflammatory and antioxidant properties. Rhapontin ameliorated the loss of dopaminergic neurons and gastrointestinal dysfunction in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mice by activating NRF2. Additionally, rhapontin treatment significantly decreased pro-inflammatory cytokines (IL-6, TNF-α, IL-1β) in the substantia nigra, striatum, and colon, whereas it increased anti-inflammatory cytokine (IL-10) levels only in the colon, indicating the involvement of gut-brain axis in its neuroprotective potential. Finally, NRF2 was identified as a key transcription factor activated by rhapontin, particularly in the colon.</p><p><strong>Conclusion: </strong>We elucidated the effects of rhapontin in MPTP-induced PD mouse models using a combination of network pharmacology analysis, behavioral assessments, immunofluorescence, ELISA, and Western blotting. Our findings revealed the multifaceted role of rhapontin in ameliorating PD through its anti-inflammatory and antioxidant properties, particularly by activating NRF2, paving the way for future research into targeted therapies for PD.</p>","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":"31 15","pages":"104875"},"PeriodicalIF":4.3,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12038550/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144044752","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":"Conversion treatment for advanced intrahepatic cholangiocarcinoma: Opportunities and challenges.","authors":"Jun-Jie Liu, Mi Zhou, Tong Yuan, Zhi-Yong Huang, Zun-Yi Zhang","doi":"10.3748/wjg.v31.i15.104901","DOIUrl":"https://doi.org/10.3748/wjg.v31.i15.104901","url":null,"abstract":"<p><p>The prevalence of intrahepatic cholangiocarcinoma (ICC) is increasing globally. Despite advancements in comprehending this intricate malignancy and formulating novel therapeutic approaches over the past few decades, the prognosis for ICC remains poor. Owing to the high degree of malignancy and insidious onset of ICC, numerous cases are detected at intermediate or advanced stages of the disease, hence eliminating the chance for surgical intervention. Moreover, because of the highly invasive characteristics of ICC, recurrence and metastasis postresection are prevalent, leading to a 5-year survival rate of only 20%-35% following surgery. In the past decade, different methods of treatment have been investigated, including transarterial chemoembolization, transarterial radioembolization, radiotherapy, systemic therapy, and combination therapies. For certain patients with advanced ICC, conversion treatment may be utilized to facilitate surgical resection and manage disease progression. This review summarizes the definition of downstaging conversion treatment and presents the clinical experience and evidence concerning conversion treatment for advanced ICC.</p>","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":"31 15","pages":"104901"},"PeriodicalIF":4.3,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12038554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144000387","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":"Evaluation of scoring systems and hematological parameters in the severity stratification of early-phase acute pancreatitis.","authors":"Pei-Na Shi, Zhang-Zhang Song, Xu-Ni He, Jie-Ming Hong","doi":"10.3748/wjg.v31.i15.105236","DOIUrl":"https://doi.org/10.3748/wjg.v31.i15.105236","url":null,"abstract":"<p><strong>Background: </strong>Acute pancreatitis (AP) is an emergency gastrointestinal disease that requires immediate diagnosis and urgent clinical treatment. An accurate assessment and precise staging of severity are essential in initial intensive therapy.</p><p><strong>Aim: </strong>To explore the prognostic value of inflammatory markers and several scoring systems [Acute Physiology and Chronic Health Evaluation II, the bedside index of severity in AP (BISAP), Ranson's score, the computed tomography severity index (CTSI) and sequential organ failure assessment] in severity stratification of early-phase AP.</p><p><strong>Methods: </strong>A total of 463 patients with AP admitted to our hospital between 1 January 2021 and 30 June 2024 were retrospectively enrolled in this study. Inflammation marker and scoring system levels were calculated and compared between different severity groups. Relationships between severity and several predictors were evaluated using univariate and multivariate logistic regression models. Predictive ability was estimated using receiver operating characteristic curves.</p><p><strong>Results: </strong>Of the 463 patients, 50 (10.80%) were classified as having severe AP (SAP). The results revealed that the white cell count significantly increased, whereas the prognostic nutritional index measured within 48 hours (PNI₄₈) and calcium (Ca²⁺) were decreased as the severity of AP increased (<i>P</i> < 0.001). According to multivariate logistic regression, C-reactive protein measured within 48 hours (CRP₄₈), Ca²⁺ levels, and PNI₄₈ were independent risk factors for predicting SAP. The area under the curve (AUC) values for the CRP₄₈, Ca²⁺, PNI₄₈, Acute Physiology and Chronic Health Evaluation II, sequential organ failure assessment, BISAP, CTSI, and Ranson scores for the prediction of SAP were 0.802, 0.736, 0.871, 0.799, 0.783, 0.895, 0.931 and 0.914, respectively. The AUC for the combined CRP₄₈ + Ca²⁺ + PNI₄₈ model was 0.892. The combination of PNI₄₈ and Ranson achieved an AUC of 0.936.</p><p><strong>Conclusion: </strong>Independent risk factors for developing SAP include CRP₄₈, Ca²⁺, and PNI₄₈. CTSI, BISAP, and the combination of PNI₄₈ and the Ranson score can act as reliable predictors of SAP.</p>","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":"31 15","pages":"105236"},"PeriodicalIF":4.3,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12038552/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144052401","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":"Multi-omics reveals the associations among the fecal metabolome, intestinal bacteria, and serum indicators in patients with hepatocellular carcinoma.","authors":"Jing Feng, Jun-Ping Wang, Jian-Ran Hu, Ping Li, Pin Lv, Hu-Cheng He, Xiao-Wei Cheng, Zheng Cao, Jia-Jing Han, Qiang Wang, Qian Su, Li-Xin Liu","doi":"10.3748/wjg.v31.i15.104996","DOIUrl":"https://doi.org/10.3748/wjg.v31.i15.104996","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC), the predominant form of primary liver cancer, is a key contributor to cancer-related deaths globally. However, HCC diagnosis solely based on blood biochemical markers lacks both sensitivity and specificity.</p><p><strong>Aim: </strong>To investigate alterations of the fecal metabolome and intestinal bacteria and reveal the correlations among differential metabolites, distinct bacteria, and serum indicators.</p><p><strong>Methods: </strong>To uncover potentially effective therapeutic targets for HCC, we utilized non-targeted liquid chromatography-mass spectrometry and high-throughput DNA sequencing targeting the 16S rRNA gene. This comprehensive approach allowed us to investigate the metabolome and microbial community structure of feces samples obtained from patients with HCC. Furthermore, we conducted an analysis to assess the interplay between the fecal metabolome and intestinal bacterial population.</p><p><strong>Results: </strong>In comparison to healthy controls, a notable overlap of 161 differential metabolites and 3 enriched Kyoto Encyclopedia of Genes and Genomes pathways was observed in the HCC12 (comprising patients with stage I and II HCC) and HCC34 groups (comprising patients with stage III and IV HCC). <i>Lachnospira</i>, <i>Streptococcus</i>, and <i>Veillonella</i> had significant differences in abundance in patients with HCC. Notably, <i>Streptococcus</i> and <i>Veillonella</i> exhibited significant correlations with serum indicators such as alpha-fetoprotein (AFP). Meanwhile, several differential metabolites [<i>e.g.</i>, 4-keto-2-undecylpyrroline, dihydrojasmonic acid, 1,8-heptadecadiene-4,6-diyne-3,10-diol, 9(S)-HOTrE] also exhibited significant correlations with serum indicators such as γ-glutamyl transferase, total bilirubin, AFP, aspartate aminotransferase, and albumin. Additionally, these two genera also had significant associations with differential metabolites such as 1,2-Dipentadecanoyl-rac-glycerol (15:0/20:0/0:0), arachidoyl ethanolamide, and 4-keto-2-undecylpyrroline.</p><p><strong>Conclusion: </strong>Our results suggest that the metabolome of fecal samples and the composition of intestinal bacteria hold promise as potential biomarkers for HCC diagnosis.</p>","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":"31 15","pages":"104996"},"PeriodicalIF":4.3,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12038548/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144030339","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}