eGastroenterology最新文献

{"title":"Ursodeoxycholic acid acts as an ileal FXR agonist in male mice with hepatic deficiency of FXR.","authors":"Zakiyah R Henry, Syeda Maliha, Veronia Basaly, Zhenning Yang, Rulaiha E Taylor, Katherine Otersen, Vik Meadows, Daniel Rizzolo, Mary Stofan, Anisha Bhattacharya, Peihong Zhou, Anita Brinker, Ill Yang, Lanjing Zhang, Laurie B Joseph, Brian Buckley, Bo Kong, Grace L Guo","doi":"10.1136/egastro-2025-100227","DOIUrl":"10.1136/egastro-2025-100227","url":null,"abstract":"<p><strong>Background: </strong>Farnesoid X receptor (FXR) has been identified as a therapeutic target for metabolic dysfunction-associated steatohepatitis (MASH). Hepatic FXR is especially critical in suppressing liver inflammation. FXR agonism and antagonism have both proven to be beneficial in the mitigation of MASH, leading to much controversy in the field, particularly regarding FXR signalling in the gut. The objective of this study was to determine the effects of ursodeoxycholic acid (UDCA), a postulated gut FXR antagonist with liver protective effects, on the mitigation and prevention of MASH development in mice with hepatic FXR deficiency.</p><p><strong>Methods: </strong>For this experiment, six-week-old to eight week-old male and female liver-specific FXR knockout (FXR^hep-/-) and control (FXR^{hep flox/flox}) mice were fed either a low-fat control diet (CTL) or a MASH 'Fast Food' diet (Western diet with 21% milk fat, 1.25% cholesterol and 34% sucrose) both supplemented with or without 0.1% (weight/weight; w/w) UDCA for 16 weeks.</p><p><strong>Results: </strong>UDCA feeding tended to reduce alanine aminotransferase levels and decrease liver lipids in the male mice. Supplementation of UDCA showed a trend towards increased UDCA and tauroursodeoxycholic acid (TUDCA) levels in serum, liver and intestine, although the male mice displayed more than twice the amount of these bile acids compared with the female mice. CTL-UDCA feeding resulted in a significant induction of <i>Fxr</i> and <i>Fgf15</i> mRNA expression in the ileum of the male mice.</p><p><strong>Conclusion: </strong>The data strongly suggest that UDCA seems to act as an FXR agonist, especially in the ileum, which contrasts with previous reports that UDCA acts as a gut FXR antagonist. In addition, UDCA seems to be exerting liver protective effects predominantly in the male mice.</p>","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"3 3","pages":"e100227"},"PeriodicalIF":0.0,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12481312/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145208519","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":"Mucosal DNA and RNA virome alterations and their interactions with human RNA and microRNA transcriptomes in colorectal polyps.","authors":"Siu Hei Shoshanna So, Wei Jiang, Yingshi Li, Georgina L Hold, Kathleen Goodrick, Ahyeon Min, Michael J Bourke, Emad M El-Omar, Xiao-Tao Jiang, Howard Chi Ho Yim","doi":"10.1136/egastro-2025-100194","DOIUrl":"10.1136/egastro-2025-100194","url":null,"abstract":"<p><strong>Background: </strong>Imbalance in the gut microbiome is known to play a role in colorectal cancer (CRC) development. Recent studies observed alterations in the faecal and mucosal DNA virome in CRC, but the role of mucosal virome including both DNA and RNA viruses in colorectal adenomas, the precursors to CRC, is unclear. Here, we investigated the human host transcriptome, mucosal virome and potential correlations between them in paired biopsy samples of colorectal polyps and their adjacent normal tissue.</p><p><strong>Methods: </strong>Paired colorectal polyp and adjacent normal mucosa biopsies from the same individuals were collected from 41 patients and subjected to comprehensive multiomics profiling. Total RNA and microRNA were analysed using whole transcriptome sequencing, while virus-like particles were enriched from paired samples and profiled via shotgun metagenomic sequencing. Integrated statistical and network analyses were performed to compare expression profiles and virome composition between polyp and adjacent normal mucosa from the same individuals, and to identify host-virome associations.</p><p><strong>Results: </strong>The host transcriptome was found to be highly altered in polyps, whereby numerous differentially expressed RNAs and microRNAs were identified compared with their paired adjacent normal mucosa from the same individuals. Pathway enrichment analysis revealed that these differentially expressed genes were enriched in metabolism and absorption, neurotransmission and cell signalling pathways. The mucosal virome was also altered in polyps, with reduced viral richness and evenness and distinct community composition compared with their paired adjacent normal mucosa from the same individuals. <i>Poxviridae</i>, <i>Retroviridae</i> and BeAn 58058 virus were enriched, whereas <i>Caudoviricetes</i> sp was depleted. Such mucosal virome signatures correlated with host transcriptomic signatures in polyps. <i>Caudoviricetes</i> sp was negatively correlated with genes involved in cancer pathways, thus is potentially CRC-protective. Conversely, <i>Poxviridae</i>, <i>Retroviridae</i> and BeAn 58058 virus were negatively correlated with genes involved in tumour suppression, thus are potentially CRC-inducing.</p><p><strong>Conclusion: </strong>This study suggests that alterations in host transcriptomes and virome of colorectal polyps are correlated, providing a foundation for future functional studies.</p>","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"3 3","pages":"e100194"},"PeriodicalIF":0.0,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439157/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145082648","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 dysbiosis is linked to severe steatosis and enhances its diagnostic performance in MASLD.","authors":"Marta Borges-Canha, Javier Centelles-Lodeiro, Ana Rita Leite, Joana Chaves, Inês Mariana Lourenço, Madalena Von-Hafe, Catarina Vale, Diana Martins, Cláudia Silva, António Carlos Ferreira, Gwen Falony, Rodrigo Liberal, Mariana Fragão-Marques, António Barros, Isabel Miranda, Adelino Leite-Moreira, Pedro Pimentel-Nunes, Sara Vieira-Silva, João Sérgio Neves","doi":"10.1136/egastro-2025-100204","DOIUrl":"10.1136/egastro-2025-100204","url":null,"abstract":"<p><strong>Background: </strong>Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading cause of chronic liver disease globally, with rising prevalence linked to metabolic syndrome (MetS). Excessive liver fat accumulation (steatosis) worsens disease progression and MASLD prognosis. Moreover, gut microbiota dysbiosis might promote steatosis, accelerating the disease progression to severe stages. Identifying gut microbiota signatures specific to steatosis severity might improve its diagnosis and inform personalised interventions in MASLD. This study aimed to characterise associations between gut microbiota composition and hepatic steatosis severity in a cohort of patients with MASLD/MetS. Ultimately, we aimed to assess the potential for microbiota features to enhance the diagnosis of severe steatosis.</p><p><strong>Methods: </strong>A cross-sectional cohort of 61 patients with MetS with extensive clinical history was recruited at different stages of MASLD. Transient elastography was used to evaluate liver fibrosis and steatosis severity. Participants' faecal microbiota were profiled using 16S rRNA gene sequencing. Statistical analyses first identified correlations between microbiota profiles and patients' phenotypes, while disentangling important confounders such as medication. Identified features were then used to build predictive models for diagnosing severe steatosis.</p><p><strong>Results: </strong>High steatosis severity was distinctly associated with a higher prevalence of the inflammation-associated Bacteroides 2 (Bact2)-enterotype, accompanied by a lower proportion of beneficial commensals (eg, <i>Akkermansia</i>) and a higher proportion of opportunistic bacteria (eg, <i>Streptococcus</i>). Patients harbouring a Bact2-enterotype reached severe steatosis at lower Fatty Liver Index (FLI) thresholds. Using Bact2-carrier status together with FLI in a predictive model significantly improved the classification of severe steatosis (accuracy 90%, receiver operating characteristics 96%) when compared with FLI alone.</p><p><strong>Conclusion: </strong>Gut microbiota composition and dysbiosis (defined as Bact2-enterotype) are distinctly associated with steatosis severity in MASLD/MetS. Patient stratification by microbiota composition enhances the diagnostic classification of severe steatosis in MASLD, suggesting a potential for personalised interventions in patients with microbiota dysbiosis.</p>","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"3 3","pages":"e100204"},"PeriodicalIF":0.0,"publicationDate":"2025-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12410686/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145016735","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":"Blood microbial DNA signature differentiates hepatocellular carcinoma from metastatic lesions.","authors":"Caitlin Guccione, Ana Carolina Dantas Machado, Fady Youssef, Isabella Angeli-Pahim, Sergio Duarte, Curtis Warren, Sawyer Farmer, Gregory Humphrey, Roland Alexander Richter, Daniel McDonald, Yuhan Weng, Adam Burgoyne, Rohit Loomba, Kit Curtius, Ali Zarrinpar, Rob Knight, Amir Zarrinpar","doi":"10.1136/egastro-2025-100193","DOIUrl":"10.1136/egastro-2025-100193","url":null,"abstract":"","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"3 3","pages":"e100193"},"PeriodicalIF":0.0,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12366555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144981011","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":"Clinical association between inflammatory bowel disease and primary sclerosing cholangitis: what changes after colectomy and liver transplantation?","authors":"Shanshan Wang, Alisa Farokhian, Bo Shen","doi":"10.1136/egastro-2025-100199","DOIUrl":"10.1136/egastro-2025-100199","url":null,"abstract":"<p><p>Inflammatory bowel disease (IBD), particularly ulcerative colitis (UC), is associated with several hepatobiliary manifestations, most importantly primary sclerosing cholangitis (PSC). The association between these entities is bidirectional, though not necessarily causal, making the underlying pathogenesis challenging to decipher. While not yet fully elucidated, current evidence suggests that genetic and immunological factors play key roles in the coexistence of IBD and PSC. In this review, we aim to provide a comprehensive analysis from a clinical perspective, evaluating the association between PSC, PSC-associated cholangiocarcinoma, orthotopic liver transplantation for PSC, IBD, colitis-associated neoplasia and restorative proctocolectomy with ileal pouch-anal anastomosis for UC. Despite efforts of data collection through population-based registries, much of the existing evidence is based on small cohorts, often with low event rates and limited follow-up durations. This makes it challenging to draw definitive conclusions. Acknowledging the variability and heterogeneity of prior studies, we aim to offer valuable insight for gastroenterologists and hepatologists managing this unique and often challenging scenario, which some authors consider a new entity: PSC-IBD. Longitudinal studies with extended follow-up periods are needed to better understand the disease course of PSC and UC, including the impact of medical therapy, the development, surveillance and management of neoplasia, and the outcomes of surgery for both bowel and liver diseases.</p>","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"3 3","pages":"e100199"},"PeriodicalIF":0.0,"publicationDate":"2025-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12336565/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144823329","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":"New insights into liver injury and regeneration from single-cell transcriptomics.","authors":"Yankai Wen, Cynthia Ju","doi":"10.1136/egastro-2025-100202","DOIUrl":"10.1136/egastro-2025-100202","url":null,"abstract":"<p><p>Recent advancements in single-cell transcriptomics have significantly enhanced our understanding of acute liver injury (ALI) and regeneration. These technologies enable high-resolution profiling of individual cells, uncovering the diverse and dynamic responses of liver cells to injury. By integrating single-cell RNA sequencing (scRNA-seq) with spatial transcriptomics, researchers have elucidated the complex cellular and molecular mechanisms driving ALI and regeneration processes. This review summarises the platforms and analytical methods of single-cell transcriptomics in liver research and discusses liver sample processing considerations for scRNA-seq, including the comparison between <i>in vivo</i> enzymatic perfusion and <i>ex vivo</i> digestion. It highlights the transformative impact of single-cell transcriptomics on ALI and regeneration studies, revealing novel insights into previously unrecognised cell subpopulations. Key discoveries include the identification of fetal-like and <i>Anxa2⁺</i> migratory hepatocytes at injury-repair interfaces, the characterisation of distinct activated hepatic stellate cell states during injury and repair phases, and the elucidation of zone-specific endothelial cell responses in <i>Wnt</i> signalling. Notable findings in macrophage heterogeneity include the discovery of <i>Trem2⁺</i> populations in both Kupffer cells and monocyte-derived macrophages, with distinct roles in injury and repair processes. The application of single-cell transcriptomics continues to hold promise for identifying novel therapeutic targets, ultimately advancing the development of novel treatment strategies for acute liver diseases.</p>","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"3 3","pages":"e100202"},"PeriodicalIF":0.0,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12306295/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144746333","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":"Advances in the treatment of transthyretin amyloidosis.","authors":"Intissar Anan","doi":"10.1136/egastro-2025-100198","DOIUrl":"10.1136/egastro-2025-100198","url":null,"abstract":"<p><p>This review aims to provide a comprehensive overview of the existing therapeutic options for managing neuropathic and/or cardiac manifestations associated with transthyretin amyloidosis (ATTR), along with investigational therapeutic candidates under evaluation in ongoing clinical trials. Additionally, emerging approaches for combating this life-threatening disease are discussed. Recent advancements in non-invasive diagnostic techniques for the detection of ATTR have facilitated improved diagnosis and identification at an earlier disease stage, thereby enhancing the potential efficacy of therapeutic interventions. Presently, there exists a range of clinically available treatments targeting ATTR, alongside investigational agents undergoing assessment in clinical trials. Therapeutic modalities encompass tetramer stabilisation, gene silencing, and ATTR fibril disruption and removal strategies. Historically, ATTR has been underdiagnosed. However, with the progression of diagnostic methodologies and the introduction of disease-modifying treatments, early diagnosis and initiation of treatment have significantly transformed the management of this condition, and effective treatment modalities have been introduced and are under development.</p>","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"3 3","pages":"e100198"},"PeriodicalIF":0.0,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12278169/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144692614","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":"Association between infection of Helicobacter pylori and the risk of reflux oesophagitis occurrence or recurrence: a systematic review and meta-analysis.","authors":"Anna Li, Yanan Zhang, Kunping Chen, Xin Quan, Kun Yin, Manli Cui, Ning Lu, Mingxin Zhang","doi":"10.1136/egastro-2024-100121","DOIUrl":"10.1136/egastro-2024-100121","url":null,"abstract":"<p><strong>Background: </strong>To investigate the correlation between infection of <i>Helicobacter pylori (H. pylori</i>) and the risk of reflux oesophagitis (RE) occurrence or recurrence.</p><p><strong>Methods: </strong>Literature was retrieved from PubMed, Embase, Web of Science and Cochrane Library databases, and the search period ranged from the time of database establishment to December 2024. Prospective cohort studies and randomised controlled trials were included for data analysis to assess the association of infection of <i>H. pylori</i> with the risk of RE occurrence and recurrence, and subgroup analyses were performed.</p><p><strong>Results: </strong>The overall risk of RE in the <i>H. pylori-</i>eradicated group was significantly higher than that in the placebo group (p<0.01). The analysis failed to detect a statistically significant difference in RE risk between the <i>H. pylori-</i>eradicated group and placebo group among different age groups, regions and disease types. The risk of RE significantly increased after eradication of <i>H. pylori</i> for >1 year (p<0.01).</p><p><strong>Conclusion: </strong>Infection of <i>H. pylori</i> in different age groups, regions and diseases may lead to the occurrence or recurrence of RE after receiving <i>H. pylori</i> eradication treatment. This correlation increased as the follow-up period extended. Although receiving <i>H. pylori</i> eradication treatment may increase the risk of RE occurrence or recurrence, doctors should take into consideration the individual situation of the patient to determine whether eradication treatment should be administered concomitantly or postponed during clinical treatment decision making.</p><p><strong>Prospero registration number: </strong>CRD 42024529321.</p>","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"3 2","pages":"e100121"},"PeriodicalIF":0.0,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12207148/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144531390","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":"Contribution of colibactin-producing Escherichia coli to colonic carcinogenesis.","authors":"Hideki Ishikawa, Ryogo Aoki, Michihiro Mutoh, Shingo Ishiguro, Takuji Tanaka, Noriyuki Miyoshi, Shingo Miyamoto, Takahiro Hamoya, Naohisa Yoshida, Keiji Wakabayashi, Kenji Watanabe","doi":"10.1136/egastro-2024-100177","DOIUrl":"10.1136/egastro-2024-100177","url":null,"abstract":"","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"3 2","pages":"e100177"},"PeriodicalIF":0.0,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12207174/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144531391","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":"Key takeaways from the updated multidisciplinary European MASLD guidelines.","authors":"Paul Horn, Frank Tacke","doi":"10.1136/egastro-2025-100196","DOIUrl":"10.1136/egastro-2025-100196","url":null,"abstract":"<p><p>The new European clinical practice guidelines from three scientific societies (European Association for the Study of the Liver, European Association for the Study of Diabetes and European Association for the Study of Obesity) on the management of metabolic dysfunction-associated steatotic liver disease (MASLD) provide detailed recommendations on diagnosis, risk stratification, monitoring strategies, treatment and prevention. Lifestyle interventions (eg, weight reduction, Mediterranean diet, exercise, alcohol abstinence) and the treatment of cardiometabolic risk factors continue to be the mainstay of treatment and prevention of the disease. Incretin mimetics that are approved to treat obesity and/or type 2 diabetes such as semaglutide and tirzepatide have benefits for ameliorating metabolic dysfunction-associated steatohepatitis (MASH). Novel developments include adapted strategies for screening (case finding) using non-invasive tests (NITs) with a focus on detecting fibrosis or cirrhosis, risk-adjusted monitoring of MASLD by NITs as well as the recommendation to use, if locally approved, the thyroid hormone receptor β-agonist resmetirom in patients with non-cirrhotic MASH fibrosis (≥F2 stage).</p>","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"3 2","pages":"e100196"},"PeriodicalIF":0.0,"publicationDate":"2025-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12161374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144287430","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}