eGastroenterology最新文献

{"title":"Causal role of the gut microbiome in certain human diseases: a narrative review.","authors":"Connor Prosty, Khaled Katergi, Jesse Papenburg, Alexander Lawandi, Todd C Lee, Hao Shi, Philip Burnham, Lee Swem, Bertrand Routy, Cedric P Yansouni, Matthew P Cheng","doi":"10.1136/egastro-2024-100086","DOIUrl":"10.1136/egastro-2024-100086","url":null,"abstract":"<p><p>Composed of an elaborate ecosystem of bacteria, fungi, viruses and protozoa residing in the human digestive tract, the gut microbiome influences metabolism, immune modulation, bile acid homeostasis and host defence. Through observational and preclinical data, the gut microbiome has been implicated in the pathogenesis of a spectrum of chronic diseases ranging from psychiatric to gastrointestinal in nature. Until recently, the lack of unequivocal evidence supporting a causal link between gut microbiome and human health outcomes incited controversy regarding its significance. However, recent randomised controlled trial (RCT) evidence in conditions, such as <i>Clostridioides difficile</i> infection<i>,</i> cancer immunotherapy and ulcerative colitis, has supported a causal relationship and has underscored the potential of the microbiome as a therapeutic target. This review delineates the RCT evidence substantiating the potential for a causal relationship between the gut microbiome and human health outcomes, the seminal observational evidence that preceded these RCTs and the remaining knowledge gaps.</p>","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"2 3","pages":"e100086"},"PeriodicalIF":0.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11770457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143411960","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":"Pancreatic incidentaloma: incidental findings from history towards the era of liquid biopsy.","authors":"J-Matthias Löhr, Miroslav Vujasinovic, Nikolaos Kartalis, Philipp Osten","doi":"10.1136/egastro-2024-100082","DOIUrl":"10.1136/egastro-2024-100082","url":null,"abstract":"<p><p>This report provides an overview of the most common diagnostic methods that bring to light incidental findings of pancreatic cancer. It reviews the impact of medical imaging and genetic assessment on the definitions of incidental findings and incidentaloma of the pancreas. For different diagnostic approaches (eg, MRI and CT) and for different affections (cysts/intraductal papillary mucinous neoplasia, solid lesions), specific guidelines have been proposed and some are established. Based on this, we summarise the differences between the traditional methods with those applied in the PANCAID project. Biomarkers, genetic predispositions, mutations and circulating tumour cells give rise to different levels of concern. The final part of the report discusses the risks and the opportunities associated with further diagnostic procedures and surgical interventions. From the ethical perspective, the most urging question is, can a screening based on liquid biopsy and blood samples open a gateway for the prevention of pancreatic cancer-even if morbidity and lethality of today's surgical interventions is still very high?</p>","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"2 3","pages":"e100082"},"PeriodicalIF":10.5,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11770461/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143411976","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":"Artificial intelligence-enabled advanced endoscopic imaging to assess deep healing in inflammatory bowel disease.","authors":"Yasuharu Maeda, Ilaria Ditonno, Miguel Puga-Tejada, Irene Zammarchi, Giovanni Santacroce, Subrata Ghosh, Marietta Iacucci","doi":"10.1136/egastro-2024-100090","DOIUrl":"10.1136/egastro-2024-100090","url":null,"abstract":"<p><p>Endoscopic remission is the primary long-term therapeutic goal in inflammatory bowel disease (IBD). The assessment of this therapeutic target typically relies on white light endoscopy (WLE) combined with histological sampling. Nonetheless, distinguishing between endoscopic mild, patchy inflammation and quiescent disease can be challenging, and discrepancies have been observed between endoscopic and histological disease activity, mainly when using WLE. Recent advances in endoscopic technologies are gradually transforming clinical practice. Dye-based chromoendoscopy and virtual chromoendoscopy are currently available in the endoscopist armamentarium, enhancing the assessment of mucosal architecture and vascular patterns, improving the visualisation of patchy inflammation and helping detect subtle dysplastic colonic lesions. Moreover, novel advanced tools, including probe-based confocal laser endomicroscopy and endocytoscopy, offer the remarkable ability to investigate the deep aspect of the gastrointestinal tract in real time, including the structure and function of the intestinal barrier and inflammatory-related alterations. Thus, these techniques can bridge the gap between endoscopy and histology, enabling the integration of novel treat-to-target strategies associated with more favourable outcomes. Artificial intelligence (AI) represents a further step forward in overcoming the limitations associated with endoscopy, including subjectivity and the requirement for expertise. Their implementation in clinical practice may enable standardised, accurate and rapid disease assessment. Moreover, AI can aid in accurately predicting responses to therapy and disease outcomes by stratifying patients' risks, thereby advancing us towards patient-centred personalised medicine. This narrative review summarises the available advanced endoscopic technologies and their integration with AI to assess IBD activity, define promising therapeutic targets and predict long-term outcomes.</p>","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"2 3","pages":"e100090"},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11770464/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143411959","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":"Characterisation of HBV and co-infection with HDV and HIV through spatial transcriptomics","authors":"Amy Cross, James M. Harris, Edward Arbe-Barnes, Colin Nixon, R. Dhairyawan, Andrew Hall, Alberto Quaglia, Fadi Issa, Patrick T F Kennedy, Jane A. McKeating, U. Gill, Dimitra Peppa","doi":"10.1136/egastro-2024-100067","DOIUrl":"https://doi.org/10.1136/egastro-2024-100067","url":null,"abstract":"The intrahepatic processes associated with chronic hepatitis B (CHB), especially in the context of hepatitis delta virus (HDV) and HIV co-infection, require a better understanding. Spatial transcriptomics can provide new insights into the complex intrahepatic biological processes, guiding new personalised treatments. Our aim is to evaluate this method characterising the intrahepatic transcriptional landscape, cellular composition and biological pathways in liver biopsy samples from patients with hepatitis B virus (HBV) and HDV or HIV co-infection.The NanoString GeoMx digital spatial profiling platform was employed to assess expression of HBV surface antigen and CD45 in formalin-fixed paraffin-embedded (FFPE) biopsies from three treatment-naïve patients with chronic HBV and HDV or HIV co-infection. The GeoMx Human Whole Transcriptome Atlas assay quantified the expression of genes enriched in specific regions of interest (ROIs). Cell type proportions within ROIs were deconvoluted using a training matrix from the human liver cell atlas. A weighted gene correlation network analysis evaluated transcriptomic signatures across sampled regions.Spatially discrete transcriptomic signatures and distinct biological pathways were associated with HBV infection/disease status and immune responses. Shared features including ‘cytotoxicity’ and ‘B cell receptor signalling’ were consistent across patients, suggesting common elements alongside individual traits. HDV/HBV co-infection exhibited upregulated genes linked to apoptosis and immune cell recruitment, whereas HIV/HBV co-infection featured genes related to interferon response regulation. Varied cellular characteristics and immune cell populations, with an abundance of γδT cells in the HDV/HBV sample, were observed within analysed regions. Transcriptional differences in hepatocyte function suggest disrupted metabolic processes in HDV/HBV co-infection potentially impacting disease progression.This proof-of-principle study shows the value of this platform in investigating the complex immune landscape, highlighting relevant host pathways to disease pathogenesis.","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"61 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141699020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mendelian randomisation analysis for intestinal disease: achievement and future.","authors":"Xixian Ruan, Tianyi Che, Xuejie Chen, Yuhao Sun, Tian Fu, Shuai Yuan, Xue Li, Jie Chen, Xiaoyan Wang","doi":"10.1136/egastro-2023-100058","DOIUrl":"10.1136/egastro-2023-100058","url":null,"abstract":"<p><p>Intestinal disease is a group of complex digestive system diseases imposing a significant burden globally. Identifying the risk factors and potential complications of intestinal disease is important for its prevention and treatment. However, traditional observational clinical studies are limited by confounding factors and reverse causation, making causal inference challenging. Mendelian randomisation (MR) method has been developed to effectively mitigate these constraints and assess the causal relationships. This review briefly introduces the MR method, summarises MR research on intestinal disease and delineates the prospective avenues for future research. Conventional risk factors, such as lifestyle behaviours (eg, physical activity, smoking and alcohol consumption), nutrients (eg, selenium), obesity markers (eg, body mass index and waist-to-hip ratio) and inflammatory biomarkers, have been validated in MR studies. Multiomics MR studies are becoming novel hotspots, which provide a theoretical foundation for the exploration of pathogenesis and the investigation of new drug targets. However, most of the recent studies are based on European individuals, and thus it is necessary to replicate the results in other ancestries. Moreover, triangulation integrating MR and other epidemiology methods is suggested as a validated paradigm for causal inference in future MR studies.</p>","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"2 2","pages":"e100058"},"PeriodicalIF":0.0,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11770446/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143411957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endoscopic resection of large non-pedunculated colorectal polyps: current standards of treatment.","authors":"Mahsa Taghiakbari, Dong Hyun Danny Kim, Roupen Djinbachian, Daniel von Renteln","doi":"10.1136/egastro-2023-100025","DOIUrl":"10.1136/egastro-2023-100025","url":null,"abstract":"<p><p>Colorectal cancer is a significant public health concern, and large non-pedunculated colorectal polyps pose a substantial risk for malignancy and incomplete resection, which may lead to interval cancer. The choice of resection technique is influenced by various factors, including polyp size, morphology, location, submucosal invasion depth and endoscopist expertise. For non-cancerous superficial large non-pedunculated polyps, conventional hot or cold snare polypectomy, endoscopic mucosal resection and endoscopic submucosal dissection are common techniques for non-surgical therapeutic endoscopic resection of these polyps. This manuscript provides a comprehensive review of literature on current endoscopic resection techniques for large non-pedunculated colorectal polyps, emphasising indications, advantages, limitations and outcomes.</p>","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"2 2","pages":"e100025"},"PeriodicalIF":0.0,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11731078/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143411956","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":"Prebiotic selection influencing inflammatory bowel disease treatment outcomes: a review of the preclinical and clinical evidence","authors":"Amin Ariaee, Sabrina Koentgen, Hannah R. Wardill, Georgina L Hold, C. Prestidge, H. Armstrong, P. Joyce","doi":"10.1136/egastro-2023-100055","DOIUrl":"https://doi.org/10.1136/egastro-2023-100055","url":null,"abstract":"Inflammatory bowel disease (IBD) is characterised by chronic inflammation in the gastrointestinal tract, with unclear aetiology but with known factors contributing to the disease, including genetics, immune responses, environmental factors and dysbiosis of the gut microbiota. Existing pharmacotherapies mainly target the inflammatory symptoms of disease, but recent research has highlighted the capacity for microbial-accessible carbohydrates that confer health benefits (ie, prebiotics) to selectively stimulate the growth of beneficial gut bacteria for improved IBD management. However, since prebiotics vary in source, chemical composition and microbiota effects, there is a clear need to understand the impact of prebiotic selection on IBD treatment outcomes. This review subsequently explores and contrasts the efficacy of prebiotics from various sources (β-fructans, galacto-oligosaccharides, xylo-oligosaccharides, resistant starch, pectin, β-glucans, glucomannans and arabinoxylans) in mitigating IBD symptomatology, when used as either standalone or adjuvant therapies. In preclinical animal colitis models, prebiotics have revealed type-dependent effects in positively modulating gut microbiota composition and subsequent attenuation of disease indicators and proinflammatory responses. While prebiotics have demonstrated therapeutic potential in animal models, clinical evidence for their precise efficacy remains limited, stressing the need for further investigation in human patients with IBD to facilitate their widespread clinical translation as microbiota-targeting IBD therapies.","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"104 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140768597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PFDN6 contributes to colorectal cancer progression via transcriptional regulation","authors":"Fenghua Xu, Lingyang Kong, Xiao Sun, WenXiang Hui, Lan Jiang, Wenxin Han, ZhiFeng Xiao, Ning Li, DongFeng Chen, Nan Zheng, Jing Han, Lei Liu","doi":"10.1136/egastro-2023-100001","DOIUrl":"https://doi.org/10.1136/egastro-2023-100001","url":null,"abstract":"Colorectal cancer (CRC) is a common cancer worldwide. Although there are several treatments for cancer, the therapeutic effect on CRC remains unsatisfactory, and it is imperative to identify new therapeutic targets.Prefoldin (PFDN) is mainly used in the cytoskeleton assembly during the folding of actin and tubulin monomers. However, whether PFDN subunits are involved in regulating the development of CRC remains to be elucidated. In this study, molecular biology, cell culture, transcriptome sequencing and other experimental techniques, combined with bioinformatics, were used to verify the regulatory effects of PFDN6 on CRC.PFDN6 expression is elevated in patients with CRC and is closely associated with the development of CRC. Knockdown of PFDN6 reduced the tumour cell number, promoted apoptosis, and inhibited the migration and invasion of CRC cells in HCT-116 and RKO cell lines. Mechanistically, differentially expressed genes and related signalling pathways in RKO cells after PFDN6 knockdown were analysed by transcriptome sequencing.PFDN6 was found to regulate the generation and development of CRC by targeting ZNF575. These results open new avenues for therapeutic interventions for patients with CRC.","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"20 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140791923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bile acids regulation of cellular stress responses in liver physiology and diseases.","authors":"Tiangang Li, Mohammad Nazmul Hasan, Lijie Gu","doi":"10.1136/egastro-2024-100074","DOIUrl":"10.1136/egastro-2024-100074","url":null,"abstract":"<p><p>Bile acids are physiological detergents and signalling molecules that are critically implicated in liver health and diseases. Dysregulation of bile acid homeostasis alters cell function and causes cell injury in chronic liver diseases. Therapeutic agents targeting bile acid synthesis, transport and signalling hold great potential for treatment of chronic liver diseases. The broad cellular and physiological impacts of pharmacological manipulations of bile acid metabolism are still incompletely understood. Recent research has discovered new links of bile acid signalling to the regulation of autophagy and lysosome biology, redox homeostasis and endoplasmic reticulum stress. These are well-conserved mechanisms that allow cells to adapt to nutrient and organelle stresses and play critical roles in maintaining cellular integrity and promoting survival. However, dysregulation of these cellular pathways is often observed in chronic liver diseases, which exacerbates cellular dysfunction to contribute to disease pathogenesis. Therefore, identification of these novel links has significantly advanced our knowledge of bile acid biology and physiology, which is needed to understand the contributions of bile acid dysregulation in disease pathogenesis, establish bile acids as diagnostic markers and develop bile acid-based pharmacological interventions. In this review, we will first discuss the roles of bile acid dysregulation in the pathogenesis of chronic liver diseases, and then discuss the recent findings on the crosstalk of bile acid signalling and cellular stress responses. Future investigations are needed to better define the roles of these crosstalks in regulating cellular function and disease processes.</p>","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"2 2","pages":""},"PeriodicalIF":10.5,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11257078/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141725196","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":"Incorporating biological and clinical insights into variant choice for Mendelian randomisation: examples and principles","authors":"S. Burgess, H. T. Cronjé","doi":"10.1136/egastro-2023-100042","DOIUrl":"https://doi.org/10.1136/egastro-2023-100042","url":null,"abstract":"Mendelian randomisation is an accessible and valuable epidemiological approach to provide insight into the causal nature of relationships between risk factor exposures and disease outcomes. However, if performed without critical thought, we may simply have replaced one set of implausible assumptions (no unmeasured confounding or reverse causation) with another set of implausible assumptions (no pleiotropy or other instrument invalidity). The most critical decision to avoid pleiotropy is which genetic variants to use as instrumental variables. Two broad strategies for instrument selection are a biologically motivated strategy and a genome-wide strategy; in general, a biologically motivated strategy is preferred. In this review, we discuss various ways of implementing a biologically motivated selection strategy: using variants in a coding gene region for the exposure or a gene region that encodes a regulator of exposure levels, using a positive control variable and using a biomarker as the exposure rather than its behavioural proxy. In some cases, a genome-wide analysis can provide important complementary evidence, even when its reliability is questionable. In other cases, a biologically-motivated analysis may not be possible. The choice of genetic variants must be informed by biological and functional considerations where possible, requiring collaboration to combine biological and clinical insights with appropriate statistical methodology.","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"103 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139638552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}