Gut最新文献

{"title":"Bioprinting functional hepatocyte organoids derived from human chemically induced pluripotent stem cells to treat liver failure","authors":"Guangya Li, Jianyu He, Jihang Shi, Xinyi Li, Lulu Liu, Xinlan Ge, Wenhan Chen, Jun Jia, Jinlin Wang, Ming Yin, Yasuyuki Sakai, Wei Sun, Hongkui Deng, Yuan Pang","doi":"10.1136/gutjnl-2024-333885","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-333885","url":null,"abstract":"Background To treat liver failure, three-dimensional (3D) bioprinting is a promising technology used to construct hepatic tissue models. However, current research on bioprinting of hepatic tissue models primarily relies on conventional single-cell-based bioprinting, where individual functional hepatocytes are dispersed and isolated within hydrogels, leading to insufficient treatment outcomes due to inadequate cell functionality. Objective Here, we aim to bioprint a hepatic tissue model using functional hepatocyte organoids (HOs) and evaluate its liver-specific functions in vitro and in vivo . Design Human chemically induced pluripotent stem cells (hCiPSCs) were used as a robust and non-genome-integrative cell source to produce highly viable and functional HOs (hCiPSC-HOs). An oxygen-permeable microwell device was used to enhance oxygen supply, ensuring high cell viability and promoting hCiPSC-HOs maturation. To maintain the long-term biofunction of hCiPSC-HOs, spheroid-based bioprinting was employed to construct hepatic tissue models (3DP-HOs). 3DP-HOs were intraperitoneally implanted in mice with liver failure. Results 3DP-HOs demonstrated enhanced cell viability when compared with a model fabricated using single-cell-based bioprinting and exhibited gene profiles closely resembling hCiPSC-HOs while maintaining liver-specific functionality. Moreover, 3DP-HOs implantation significantly improved survival in mice with CCl4-induced acute-on-chronic liver failure and also Fah−/− mice with liver failure. 3DP-HOs significantly reduced liver injury, inflammation and fibrosis indices while promoting liver regeneration and biofunction expression. Conclusion Our bioprinted hepatic tissue model exhibits remarkable therapeutic efficacy for liver failure and holds great potential for clinical research in the field of liver regenerative medicine. All data relevant to the study are included in the article or uploaded as supplementary information.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"28 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143538437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut microbiota-related neuroinflammation at the crossroad of food reward alterations: implications for eating disorders.","authors":"Sabrina J P Huwart, Nuria Morales-Puerto, Amandine Everard","doi":"10.1136/gutjnl-2024-333397","DOIUrl":"10.1136/gutjnl-2024-333397","url":null,"abstract":"<p><p>The link between gut microbiome and eating behaviours, especially palatable food intake, is a growing focus of scientific investigation. The complex ecosystem of microorganisms in the gut influences host metabolism, immune function and neurobehavioural signalling. This review explores the role of neuroinflammation in dysregulations of food-induced reward signalling and the potential causal role of the gut microbiota on these proinflammatory processes. Particular attention is given to eating disorders (ED, specifically anorexia nervosa, binge eating disorder and bulimia nervosa) and potential links with the gut microbiota, food reward alterations and neuroinflammation. Finally, we propose gut microbiota modulation as a promising therapeutic strategy in food reward alterations and ED.</p>","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":""},"PeriodicalIF":23.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"24-Nor-ursodeoxycholic acid improves intestinal inflammation by targeting TH17 pathogenicity and transdifferentiation","authors":"Ci Zhu, Nicole Boucheron, Osamah Al-Rubaye, Brian K Chung, Liv Wenche Thorbjørnsen, Thomas Köcher, Michael Schuster, Thierry Claudel, Emina Halilbasic, Victoria Kunczer, Fanziska Muscate, Lois L Cavanagh, Darina Waltenberger, Alexander Lercher, Anna Ohradanova-Repic, Philipp Schatzlmaier, Tatjana Stojakovic, Hubert Scharnagl, Andreas Bergthaler, Hannes Stockinger, Samuel Huber, Christoph Bock, Lukas Kenner, Tom H Karlsen, Wilfried Ellmeier, Michael Trauner","doi":"10.1136/gutjnl-2024-333297","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-333297","url":null,"abstract":"Background 24-Nor-ursodeoxycholic acid (NorUDCA) is a novel therapeutic bile acid for treating immune-mediated cholestatic liver diseases, such as primary sclerosing cholangitis (PSC). Objective Since PSC strongly associates with T helper-type-like 17 (TH17)-mediated intestinal inflammation, we explored NorUDCA’s immunomodulatory potential on TH17 cells. Design NorUDCA’s impact on TH17 differentiation was assessed using a CD4+TNaive adoptive transfer mouse model, and on intraepithelial TH17 pathogenicity and transdifferentiation using an αCD3 stimulation model combined with interleukin-17A-fate-mapping. Mechanistic studies used molecular and multiomics approaches, flow cytometry and metabolic assays with pathogenic (p) TH17. Pathogenicity of pTH17 exposed to NorUDCA in vitro was evaluated following adoptive transfer in intestinal tissues or the central nervous system (CNS). Key findings were validated in an αCD3-stimulated humanised NSG mouse model reconstituted with peripheral blood mononuclear cells from patients with PSC. Results NorUDCA suppressed TH17 effector function and enriched regulatory T cell (Treg) abundance upon CD4+TNaive cell transfer. NorUDCA mitigated intraepithelial TH17 pathogenicity and decreased the generation of proinflammatory ‘TH1-like-TH17’ cells, and enhanced TH17 transdifferentiation into Treg and Tr1 (regulatory type 1) cells in the αCD3-model. In vivo ablation revealed that Treg induction is crucial for NorUDCA’s anti-inflammatory effect on TH17 pathogenicity. Mechanistically, NorUDCA restrained pTH17 effector function and simultaneously promoted functional Treg formation in vitro , by attenuating a glutamine-mTORC1-glycolysis signalling axis. Exposure of pTH17 to NorUDCA dampened their pathogenicity and expansion in the intestine or CNS upon transfer. NorUDCA’s impact on TH17 inflammation was corroborated in the humanised NSG mouse model. Conclusion NorUDCA restricts TH17 inflammation in multiple mouse models, potentiating future clinical applications for treating TH17-mediated intestinal diseases and beyond. Data are available upon reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"32 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143538436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnosis of nasopharyngeal disease during upper GI endoscopy","authors":"Wei Xie, Qian Yin, Hong Fang, Kai-yan Yang, Hai-bo Xue, Huimin Zheng, Pan Li","doi":"10.1136/gutjnl-2024-334528","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-334528","url":null,"abstract":"Nasopharyngeal examination is usually not part of upper gastrointestinal (GI) endoscopy but could be used to potentially diagnose early lesions in this area. We present preliminary results of nasopharyngeal inspection either at the start (insertion) or after (withdrawal) performance of upper GI endoscopy in 1550 patients, with a technical success rate of 97.6%. Two early-stage cancer cases were identified, and 439 patients had nasopharyngeal diseases of variable relevance. Mild complications were observed in 6.1%. This technique should be systematically evaluated for screening in high-risk areas. Malignant nasopharyngeal diseases, particularly nasopharyngeal carcinoma, are challenging to detect due to their non-specific symptoms, the anatomical location of the nasopharynx and the lack of cost-effective routine screening methods.1 Consequently, over 70% of nasopharyngeal carcinoma cases are diagnosed at advanced stages (III or IV) during the initial presentation,2 with a 5-year overall survival of about 50%. However, when nasopharyngeal carcinoma is detected at early stages, the 5-year overall survival approaches 95% or higher.3 4 The current diagnostic gold standards—rhinolaryngoscopy and transnasal gastroscopy with histological examination—are unsuitable for routine screening due to their lack of cost-effectiveness and, as diagnostic tools, suffer from technical limitations such as image sensor size, optical fibre count, field of view and lack of magnification capability, which significantly reduce image quality.5 6 Upper GI gastroscopy, one of the most commonly performed diagnostic procedures, is the standard method for diagnosing various GI diseases and is used for screening in some high-risk areas for oesophageal or gastric cancer.7 8 Studies have demonstrated that systematic assessment of the pharynx during gastroscopy can enhance the detection of pre-cancerous and incidental otolaryngologic lesions.9 10 However, it was previously thought that the nasopharynx could not be visualised during upper GI endoscopy unless a nasal entry was performed.11 Since most malignant nasopharyngeal diseases occur …","PeriodicalId":12825,"journal":{"name":"Gut","volume":"27 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143517970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"E-twenty-six-specific sequence variant 5 (ETV5) facilitates hepatocellular carcinoma progression and metastasis through enhancing polymorphonuclear myeloid-derived suppressor cell (PMN-MDSC)-mediated immunosuppression","authors":"Zerui Zhang, Wenjie Huang, Dian Hu, Junqing Jiang, Jiaqian Zhang, Zhangfan Wu, Junjie Wen, Xiangyuan Luo, Yijun Wang, Mengyu Sun, Siwen Li, Yufei Wang, Danfei Liu, Xiaoping Chen, Bixiang Zhang, Huifang Liang, Yiwei Li, Bifeng Liu, Shuai Wang, Xiao Xu, Yongzhan Nie, Kaichun Wu, Daiming Fan, Limin Xia","doi":"10.1136/gutjnl-2024-333944","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-333944","url":null,"abstract":"Background Despite the success of immune checkpoint blockade, a lack of understanding of the hepatocellular carcinoma (HCC) immune microenvironment impedes its development. Objective We aim to elucidate the essential function of E-twenty-six-specific sequence variant 5 (ETV5) in regulating the immune microenvironment in HCC. Design Humanised mouse models, murine orthotopic models and diethylnitrosamine/carbon tetrachloride (DEN/CCl4)-induced HCC models were used to examine the function of ETV5. The downstream targets of ETV5 were screened using chromatin immunoprecipitation sequencing, CUT&Tag and RNA sequencing. Immune cells were examined using flow cytometry and immunofluorescence. S100 calcium-binding protein A9 (S100A9) was targeted by neutralising antibodies. Results Overexpression of ETV5 in HCC cells facilitated HCC metastasis and immune escape by recruiting and enhancing the immunosuppressive capabilities of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs). Mechanistically, ETV5 transactivated programmed death ligand 1 (PD-L1) and S100A9 expression. Inhibition of S100A9 or myeloid-specific knockout of toll-like receptor 4 (TLR4)/receptor for advanced glycation endproducts (RAGE), the receptors of S100A9, impeded ETV5-induced PMN-MDSC recruitment. Meanwhile, S100A9 within the tumour microenvironment elevated ETV5 expression via the extracellular signal-regulated kinase (ERK)/nuclear factor-kappa B pathway. Additionally, ETV5 transcriptionally upregulated PD-L1 in MDSCs as well, thereby augmenting their immunosuppressive functions. Myeloid-specific Etv5 knockout attenuated HCC progression. We developed monoclonal neutralising-S100A9 antibodies that effectively inhibited ETV5-mediated PMN-MDSC infiltration. Synergistic application of anti-S100A9 or TLR4/RAGE inhibitors with anti-PD-L1 therapy significantly suppressed ETV5-mediated HCC progression. Conclusion ETV5 facilitates HCC progression and metastasis by promoting the recruitment, infiltration and activation of PMN-MDSCs. Synergistic application of anti-S100A9 or TLR4/RAGE inhibitors with anti-PD-L1 therapy holds great promise as an effective combinational treatment strategy for ETV5-positive HCC. Data are available upon reasonable request. Data, analytical methods and study materials will be available from the corresponding author upon request.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"30 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143517968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut microbial-derived N-acetylmuramic acid alleviates colorectal cancer via the AKT1 pathway","authors":"Mengyao Hu, Yi Xu, Yuqing Wang, Zhenhe Huang, Lei Wang, Fanan Zeng, Bowen Qiu, Zefeng Liu, Peibo Yuan, Yu Wan, Shuang Ge, Dian Zhong, Siyu Xiao, Rongrong Luo, Jiaqi He, Meiling Sun, Xiaoduan Zhuang, Nannan Guo, Chunhui Cui, Jie Gao, Hongwei Zhou, Xiaolong He","doi":"10.1136/gutjnl-2024-332891","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-332891","url":null,"abstract":"Background Gut microbial metabolites are recognised as critical effector molecules that influence the development of colorectal cancer (CRC). Peptidoglycan fragments (PGFs) produced by microbiota play a crucial role in maintaining intestinal homeostasis, but their role in CRC remains unclear. Objective Here, we aimed to explore the potential contribution of PGFs in intestinal tumourigenesis. Design The relative abundance of peptidoglycan synthase and hydrolase genes was assessed by metagenomic analysis. Specific PGFs in the faeces and serum of CRC patients were quantified using targeted mass spectrometry. The effects of PGF on intestinal tumourigenesis were systematically evaluated using various murine models of CRC and organoids derived from CRC patients. Downstream molecular targets were screened and evaluated using proteome microarray, transcriptome sequencing and rescue assays. Results Metagenomic analysis across seven independent cohorts (n=1121) revealed a comprehensive reduction in peptidoglycan synthase gene relative abundance in CRC patients. Targeted mass spectrometry identified significant depletion of a specific PGF, N-acetylmuramic acid (NAM) in CRC patients, which decreased as tumours progressed (p<0.001). NAM significantly inhibits intestinal tumourigenesis in various models, including Apc Min/+, AOM/DSS-treated and MC38 tumour-bearing mice. Additionally, NAM inhibits the growth of patient-derived CRC organoids in a concentration-dependent manner. Mechanistically, NAM inhibits the activation of AKT1 by directly binding to it and blocking its phosphorylation, which is a partial mediator of NAM’s anticancer effects. Conclusion The PGF NAM protects against intestinal tumourigenesis by targeting the AKT1 signalling pathway. NAM may serve as a novel potential preventive and therapeutic biomarker against CRC. Data are available upon reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information. All data relevant to the study are included in the article or uploaded as supplementary information. Data are available on reasonable request. Transcriptome data are available in the Genome Sequence Archive (GSA) database: Bioproject PRJCA025871. The metagenomic sequencing data reported in this paper has been deposited in the European Nucleotide Archive under the study accession number PRJEB81237. Raw data not included therein can be obtained with the consent of the corresponding author.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"3 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143517966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glucagon-like peptide-1 receptor agonist use is associated with a lower risk of major adverse liver-related outcomes: a meta-analysis of observational cohort studies","authors":"Ciro Celsa, Grazia Pennisi, Adele Tulone, Giacinta Ciancimino, Marco Vaccaro, Giuseppe Infantino, Gabriele Di Maria, David J Pinato, Giuseppe Cabibbo, Marco Enea, Alessandro Mantovani, Herbert Tilg, Giovanni Targher, Calogero Cammà, Salvatore Petta","doi":"10.1136/gutjnl-2024-334591","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-334591","url":null,"abstract":"Background Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have shown promising effects on liver histology in phase 2 trials enrolling patients with metabolic dysfunction-associated steatotic liver disease. However, the impact of GLP-1RAs on the long-term risk of major adverse liver-related outcomes (MALOs) remains uncertain. Objective We performed a meta-analysis of observational cohort studies to quantify the magnitude and direction of the association between GLP-1RA use and MALOs in people with type 2 diabetes (T2D). Design We systematically searched eligible cohort studies comparing GLP-1RA new users versus users of other glucose-lowering medications. The primary outcome was the cumulative incidence rates of MALOs. Secondary outcomes included hepatic decompensation events, hepatocellular carcinoma (HCC) and liver-related mortality. Random-effects models were used to calculate incidence rate ratios (IRRs). Results 11 retrospective cohort studies with aggregate data on 1 467 220 patients with T2D (647 903 GLP-1RA new users, 819 317 non-users) were included. GLP-1RA use was significantly associated with a lower risk of MALOs (IRR 0.71, 95% CI 0.57 to 0.88) and hepatic decompensation (IRR 0.70, 95% CI 0.52 to 0.94). Association with reduced risk of HCC was also observed (IRR 0.82, 95% CI 0.61 to 1.11). Compared with other antidiabetic medications, GLP-1RAs showed superior effectiveness versus SGLT2 inhibitors in preventing MALOs (IRR 0.93, 95% CI 0.87 to 0.99), versus DPP-4 inhibitors in preventing hepatic decompensation (IRR 0.74, 95% CI 0.66 to 0.83) and versus insulin therapy in preventing HCC (IRR 0.32, 95% CI 0.13 to 0.80). Conclusions GLP-1RA use is associated with a lower risk of liver-related complications and hepatic decompensation in people with T2D. These findings suggest a role of GLP-1RAs in preventing liver-related complications beyond their beneficial cardiometabolic effects. Data are available on reasonable request. All supporting data of the meta-analysis are available within the article (and in the online-only supplementary material).","PeriodicalId":12825,"journal":{"name":"Gut","volume":"51 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143517969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rate of suitable cases for primary EUS-guided biliary drainage in distal malignant biliary obstruction","authors":"Ji Young Bang, Maryam Faraj Agha, Robert Hawes, Shyam Varadarajulu","doi":"10.1136/gutjnl-2025-334979","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-334979","url":null,"abstract":"Endoscopic ultrasound (EUS) has been suggested as the primary modality in lieu of endoscopic retrograde cholangiopancreatography (ERCP) for drainage of malignant distal biliary obstruction. However, the presence of a dilated bile duct (≥12 mm) is a prerequisite for the success of the EUS approach. In a retrospective study, we found that 44.9% of 439 ERCP patients over a 3-year period had insufficiently dilated bile duct that was not conducive for an EUS-based intervention. 29 patients were treated by a salvage EUS approach, with median bile duct diameter of 16 mm (IQR 13–18 mm). Although indispensable as a rescue technique, adopting current techniques and technology, this study does not suggest a universal primary role for EUS in this setting. Although ERCP is the preferred therapeutic strategy for malignant distal biliary obstruction, duodenal invasion by tumour can limit technical success. Also, stent dysfunction from tumour ingrowth and post-ERCP pancreatitis are well recognised limitations. Since the early 2000s, EUS-guided biliary drainage (EUS-BD) has emerged as a promising treatment alternative for ERCP. The ability to bypass tumour invasion and avoid instrumentation of the pancreatic duct increases the likelihood of technical success and minimises risk for pancreatitis. A recent meta-analysis of six randomised controlled trials (RCT) comparing EUS and ERCP involving 570 subjects found that patients undergoing EUS-BD required fewer reinterventions and had reduced risk of postprocedure pancreatitis.1 Given these promising observations, it has been suggested that EUS could potentially replace ERCP as the primary treatment modality. However, technical manoeuvres such as accessing the bile duct using a 19-gauge fine needle aspiration (FNA) device to enable guidewire passage or cauterised delivery tip to facilitate lumen-apposing metal stent (LAMS) placement require the presence of a dilated common bile duct (CBD). In two of six RCTs, CBD diameter of ≥12 mm was specified as eligibility criteria …","PeriodicalId":12825,"journal":{"name":"Gut","volume":"36 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143506862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of live biotherapeutic products: a position statement of Asia-Pacific Microbiota Consortium","authors":"Ching-Hung Tseng, Sunny Wong, Jun Yu, Yeong Yeh Lee, Jun Terauchi, Hsin-Chih Lai, Jiing-Chyuan Luo, Cheng Yen Kao, Sung-Liang Yu, Jyh-Ming Liou, Deng-Chyang Wu, Ming-Chih Hou, Ming-Shiang Wu, Jiunn-Jong Wu, Joseph J Y Sung, Emad M El-Omar, Chun-Ying Wu","doi":"10.1136/gutjnl-2024-334501","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-334501","url":null,"abstract":"Objective Live biotherapeutic products (LBPs) are biological products composed of living micro-organisms, developed to prevent, treat, or cure diseases. Examples include cultured strains of Akkermansia muciniphila and Christensenella minuta , as well as treatments using purified Firmicutes spores for recurrent Clostridioides difficile infections. There is a need for guidelines over the increasing interest in developing LBPs. A panel of microbiome experts from Asia-Pacific countries articulates their perspectives on key considerations for LBP development. Design Experts in microbiome research, microbiology, gastroenterology, internal medicine and biotherapeutics industry were invited to form a panel. During the 2023 Inauguration Conference of the Asia-Pacific Microbiota Consortium, an organised, iterative roundtable discussion was conducted to build expert consensus on critical issues surrounding the development of LBP. Results The consensus statements were organised into three main aspects: (a) rationales of LBP development, (b) preclinical studies and (c) preparation for clinical studies. The panel strongly recommended to prioritise human-derived and food-sourced strains for development, with indications based on clinical need and efficacy shown in studies. Preclinical evaluation should involve thorough screening, genotyping and phenotyping, as well as comprehensive in vitro and animal studies to assess functional mechanisms and microbiological safety. Rigorous cell banking practices and genetic monitoring are essential to ensure product consistency and safety throughout the manufacturing process. Clinical trials, including postmarketing surveillance, must be carefully designed and closely monitored, with robust safety and risk management protocols in place. Conclusions The development of LBP should be approached with a strong emphasis on microbiological evaluation, clinical relevance, scientific mechanisms and safety at every stage. These measures are essential to ensure the safety, effectiveness and long-term success of the product.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"26 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143506864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serological screening for coeliac disease in an adult general population: the HUNT study","authors":"Ina Lervåg Andersen, Polina Lukina, Ole T Dyrli, Rolf Anton Klaasen, David John Warren, Nils Bolstad, Patricia Mjønes, Elin Rønne, Rasmus Iversen, Ludvig M Sollid, Knut E A Lundin, Eivind Ness-Jensen","doi":"10.1136/gutjnl-2024-333886","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-333886","url":null,"abstract":"Background A large proportion of individuals with coeliac disease (CeD) remain undiagnosed. Objective The aim of this study was to assess serological screening for CeD in the adult general population. Design The study was based on the fourth Trøndelag Health Study, a population-based study performed 2017–2019 in Nord-Trøndelag County, Norway, including 56 042 participants >20 years of age (54% participation rate). Serum samples were analysed with a dual antitransglutaminase 2 (TG2) IgA and IgG assay and seropositive participants were invited to endoscopy with duodenal biopsies. A CeD diagnosis was given if mucosal damage (Marsh grade 3) was found. Results Histological evaluation of 657 seropositive participants confirmed CeD in 423. The positive predictive value (PPV) of a positive TG2 IgA was 73.3% (95% CI 69.7% to 77.0%) for biopsy-confirmed CeD. TG2 IgA ≥10 times the upper limit of normal (ULN), as used in the no-biopsy approach in children, increased the PPV to 88.1% (95% CI 84.8% to 91.4%). Primary TG2 IgG response was found in 87 participants, five of whom had biopsy-confirmed CeD. One of the participants with CeD primarily responding with TG2 IgG was IgA deficient. The PPV of a positive TG2 IgG was 5.8% (95% CI 1.9% to 12.9%) and of TG2 IgG ≥10× ULN was 9.5% (95% CI 1.2% to 30.4%) for biopsy-confirmed CeD in TG2 IgA-negative individuals. Conclusion The TG2 IgA assay showed excellent abilities as a screening tool for CeD in the adult general population. However, the diagnostic accuracy of TG2 IgG was too poor for selectively identifying individuals with CeD. Data are available upon reasonable request. Researchers with a PhD associated with Norwegian research institutes can apply for the use of HUNT material: data and samples - given approval by a Regional Committee for Medical and Health Research Ethics. Researchers from other countries are welcome to apply in cooperation with a Norwegian Principle Investigator. Access to the requested HUNT material is given after the application is approved of by HUNTs Data Access Committee (DAC) and an agreement is signed. The agreement gives the researcher(s) the right to research a specific topic for a limited time period and to publish a decided upon number of articles. For data information contact: HUNT Research Centre Forskningsveien 27600 Levanger, Norway. Phone +47 74 07 51 80 | +47 74 01 92 40 | +47 407 90 010. Mail: kontakt@hunt.ntnu.no","PeriodicalId":12825,"journal":{"name":"Gut","volume":"187 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143506817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}