Pub Date : 2024-10-01Epub Date: 2024-08-29DOI: 10.1136/egastro-2024-100096
Meihua Hao, Sara C Sebag, Qingwen Qian, Ling Yang
Endocrine and exocrine functions of the pancreas control nutritional absorption, utilisation and systemic metabolic homeostasis. Under basal conditions, the lysosome is pivotal in regulating intracellular organelles and metabolite turnover. In response to acute or chronic stress, the lysosome senses metabolic flux and inflammatory challenges, thereby initiating the adaptive programme to re-establish cellular homeostasis. A growing body of evidence has demonstrated the pathophysiological relevance of the lysosomal stress response in metabolic diseases in diverse sets of tissues/organs, such as the liver and the heart. In this review, we discuss the pathological relevance of pancreatic lysosome stress in diabetes mellitus. We begin by summarising lysosomal biology, followed by exploring the immune and metabolic functions of lysosomes and finally discussing the interplay between lysosomal stress and the pathogenesis of pancreatic diseases. Ultimately, our review aims to enhance our understanding of lysosomal stress in disease pathogenesis, which could potentially lead to the discovery of innovative treatment methods for these conditions.
{"title":"Lysosomal physiology and pancreatic lysosomal stress in diabetes mellitus.","authors":"Meihua Hao, Sara C Sebag, Qingwen Qian, Ling Yang","doi":"10.1136/egastro-2024-100096","DOIUrl":"10.1136/egastro-2024-100096","url":null,"abstract":"<p><p>Endocrine and exocrine functions of the pancreas control nutritional absorption, utilisation and systemic metabolic homeostasis. Under basal conditions, the lysosome is pivotal in regulating intracellular organelles and metabolite turnover. In response to acute or chronic stress, the lysosome senses metabolic flux and inflammatory challenges, thereby initiating the adaptive programme to re-establish cellular homeostasis. A growing body of evidence has demonstrated the pathophysiological relevance of the lysosomal stress response in metabolic diseases in diverse sets of tissues/organs, such as the liver and the heart. In this review, we discuss the pathological relevance of pancreatic lysosome stress in diabetes mellitus. We begin by summarising lysosomal biology, followed by exploring the immune and metabolic functions of lysosomes and finally discussing the interplay between lysosomal stress and the pathogenesis of pancreatic diseases. Ultimately, our review aims to enhance our understanding of lysosomal stress in disease pathogenesis, which could potentially lead to the discovery of innovative treatment methods for these conditions.</p>","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"2 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11542681/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142607719","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}
Pub Date : 2024-10-01Epub Date: 2024-12-09DOI: 10.1136/egastro-2024-100104
Hui Gao, Yanchao Jiang, Ge Zeng, Nazmul Huda, Themis Thoudam, Zhihong Yang, Suthat Liangpunsakul, Jing Ma
Alcohol-associated liver disease (ALD) is a growing global health concern and its prevalence and severity are increasing steadily. While bacterial endotoxin translocation into the portal circulation is a well-established key factor, recent evidence highlights the critical role of sterile inflammation, triggered by diverse stimuli, in alcohol-induced liver injury. This review provides a comprehensive analysis of the complex interactions within the hepatic microenvironment in ALD. It examines the contributions of both parenchymal cells, like hepatocytes, and non-parenchymal cells, such as hepatic stellate cells, Kupffer cells, neutrophils, and liver sinusoidal endothelial cells, in driving the progression of the disease. Additionally, we explored the involvement of key mediators, including cytokines, chemokines and inflammasomes, which regulate inflammatory responses and promote liver injury and fibrosis. A particular focus has been placed on extracellular vesicles (EVs) as essential mediators of intercellular communication both within and beyond the liver. These vesicles facilitate the transfer of signalling molecules, such as microRNAs and proteins, which modulate immune responses, fibrogenesis and lipid metabolism, thereby influencing disease progression. Moreover, we underscore the importance of organ-to-organ crosstalk, particularly in the gut-liver axis, where dysbiosis and increased intestinal permeability lead to microbial translocation, exacerbating hepatic inflammation. The adipose-liver axis is also highlighted, particularly the impact of adipokines and free fatty acids from adipose tissue on hepatic steatosis and inflammation in the context of alcohol consumption.
{"title":"Cell-to-cell and organ-to-organ crosstalk in the pathogenesis of alcohol-associated liver disease.","authors":"Hui Gao, Yanchao Jiang, Ge Zeng, Nazmul Huda, Themis Thoudam, Zhihong Yang, Suthat Liangpunsakul, Jing Ma","doi":"10.1136/egastro-2024-100104","DOIUrl":"10.1136/egastro-2024-100104","url":null,"abstract":"<p><p>Alcohol-associated liver disease (ALD) is a growing global health concern and its prevalence and severity are increasing steadily. While bacterial endotoxin translocation into the portal circulation is a well-established key factor, recent evidence highlights the critical role of sterile inflammation, triggered by diverse stimuli, in alcohol-induced liver injury. This review provides a comprehensive analysis of the complex interactions within the hepatic microenvironment in ALD. It examines the contributions of both parenchymal cells, like hepatocytes, and non-parenchymal cells, such as hepatic stellate cells, Kupffer cells, neutrophils, and liver sinusoidal endothelial cells, in driving the progression of the disease. Additionally, we explored the involvement of key mediators, including cytokines, chemokines and inflammasomes, which regulate inflammatory responses and promote liver injury and fibrosis. A particular focus has been placed on extracellular vesicles (EVs) as essential mediators of intercellular communication both within and beyond the liver. These vesicles facilitate the transfer of signalling molecules, such as microRNAs and proteins, which modulate immune responses, fibrogenesis and lipid metabolism, thereby influencing disease progression. Moreover, we underscore the importance of organ-to-organ crosstalk, particularly in the gut-liver axis, where dysbiosis and increased intestinal permeability lead to microbial translocation, exacerbating hepatic inflammation. The adipose-liver axis is also highlighted, particularly the impact of adipokines and free fatty acids from adipose tissue on hepatic steatosis and inflammation in the context of alcohol consumption.</p>","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"2 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11674000/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142904275","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}
Pub Date : 2024-10-01DOI: 10.1136/egastro-2024-100098
Fernanda Raya Tonetti, Alvaro Eguileor, Cristina Llorente
Goblet cells (GCs) are specialised guardians lining the intestine. They play a critical role in gut defence and immune regulation. GCs continuously secrete mucus creating a physical barrier to protect from pathogens while harbouring symbiotic gut bacteria adapted to live within the mucus. GCs also form specialised GC-associated passages in a dynamic and regulated manner to deliver luminal antigens to immune cells, promoting gut tolerance and preventing inflammation. The composition of gut bacteria directly influences GC function, highlighting the intricate interplay between these components of a healthy gut. Indeed, imbalances in the gut microbiome can disrupt GC function, contributing to various gastrointestinal diseases like colorectal cancer, inflammatory bowel disease, cystic fibrosis, pathogen infections and liver diseases. This review explores the interplay between GCs and the immune system. We delve into the underlying mechanisms by which GC dysfunction contributes to the development and progression of gastrointestinal diseases. Finally, we examine current and potential treatments that target GCs and represent promising avenues for further investigation.
{"title":"Goblet cells: guardians of gut immunity and their role in gastrointestinal diseases.","authors":"Fernanda Raya Tonetti, Alvaro Eguileor, Cristina Llorente","doi":"10.1136/egastro-2024-100098","DOIUrl":"10.1136/egastro-2024-100098","url":null,"abstract":"<p><p>Goblet cells (GCs) are specialised guardians lining the intestine. They play a critical role in gut defence and immune regulation. GCs continuously secrete mucus creating a physical barrier to protect from pathogens while harbouring symbiotic gut bacteria adapted to live within the mucus. GCs also form specialised GC-associated passages in a dynamic and regulated manner to deliver luminal antigens to immune cells, promoting gut tolerance and preventing inflammation. The composition of gut bacteria directly influences GC function, highlighting the intricate interplay between these components of a healthy gut. Indeed, imbalances in the gut microbiome can disrupt GC function, contributing to various gastrointestinal diseases like colorectal cancer, inflammatory bowel disease, cystic fibrosis, pathogen infections and liver diseases. This review explores the interplay between GCs and the immune system. We delve into the underlying mechanisms by which GC dysfunction contributes to the development and progression of gastrointestinal diseases. Finally, we examine current and potential treatments that target GCs and represent promising avenues for further investigation.</p>","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"2 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11542612/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634002","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}
Pub Date : 2024-09-11eCollection Date: 2024-09-01DOI: 10.1136/egastro-2024-100105
Yamin Lai, Jiachun Pan, Kaixin Peng, Dong Wu, Li Wen
{"title":"Rare cause of recurrent acute pancreatitis in teenage man.","authors":"Yamin Lai, Jiachun Pan, Kaixin Peng, Dong Wu, Li Wen","doi":"10.1136/egastro-2024-100105","DOIUrl":"10.1136/egastro-2024-100105","url":null,"abstract":"","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"2 3","pages":"e100105"},"PeriodicalIF":0.0,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11770465/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143411977","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}
Pub Date : 2024-09-10eCollection Date: 2024-09-01DOI: 10.1136/egastro-2024-100086
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
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 Clostridioides difficile infection, 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.
{"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}
Pub Date : 2024-09-09eCollection Date: 2024-09-01DOI: 10.1136/egastro-2024-100082
J-Matthias Löhr, Miroslav Vujasinovic, Nikolaos Kartalis, Philipp Osten
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?
{"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":0.0,"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}
Pub Date : 2024-08-01eCollection Date: 2024-09-01DOI: 10.1136/egastro-2024-100090
Yasuharu Maeda, Ilaria Ditonno, Miguel Puga-Tejada, Irene Zammarchi, Giovanni Santacroce, Subrata Ghosh, Marietta Iacucci
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.
{"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}
Pub Date : 2024-07-01DOI: 10.1136/egastro-2024-100067
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
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.
{"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}
Pub Date : 2024-06-17eCollection Date: 2024-04-01DOI: 10.1136/egastro-2023-100058
Xixian Ruan, Tianyi Che, Xuejie Chen, Yuhao Sun, Tian Fu, Shuai Yuan, Xue Li, Jie Chen, Xiaoyan Wang
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.
{"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}