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Bacteria as key players in primary sclerosing cholangitis?
Peter Fickert
doi : 10.1136/gutjnl-2022-327876
April 2023 - Volume 72 - 4
Refining genetic and molecular classifications to facilitate breakthrough treatments in intrahepatic cholangiocarcinoma: are we there yet?
Satoru Morita, Dan G Duda
Human defensin 5-based compounds: a new approach to fight obesity?
Marc Claret, Ruben Nogueiras
GWAS meta-analysis of 16 790 patients with Barrett’s oesophagus and oesophageal adenocarcinoma identifies 16 novel genetic risk loci and provides insights into disease aetiology beyond the single marker level
Julia Schröder, Laura Chegwidden, Carlo Maj, Jan Gehlen, Jan Speller, Anne C Böhmer, Oleg Borisov, Timo Hess, Nicole Kreuser, Marino Venerito, Hakan Alakus, Andrea May, Christian Gerges, Thomas Schmidt, Rene Thieme, Dominik Heider, Axel M Hillmer, Julian Reingruber, Orestis Lyros, Arne Dietrich, Albrecht Hoffmeister, Matthias Mehdorn, Florian Lordick, Gertraud Stocker, Michael Hohaus, Daniel Reim, Jennis Kandler, Michaela Müller, Alanna Ebigbo, Claudia Fuchs, Christiane J Bruns, Arnulf H Hölscher, Hauke Lang, Peter P Grimminger, Dani Dakkak, Yogesh Vashist, Sandra May, Siegfried Görg, Andre Franke, David Ellinghaus, Sara Galavotti, Lothar Veits, Josef Weismüller, Jens Dommermuth, Udo Benner, Thomas Rösch, Helmut Messmann, Brigitte Schumacher, Horst Neuhaus, Carsten Schmidt, Thaddäus T Wissinowski, Markus M Nöthen, Wellcome Trust Case Control Consortium 2 (WTCCC2), Esophageal Adenocarcinoma Genetics Consortium (EAGLE), Barrett's and Esophageal Adenocarcinoma Consortium (BEACON), Jing Dong, Jue-Sheng Ong, Matthew F Buas, Aaron P Thrift, Thomas L Vaughan, Ian Tomlinson, David C Whiteman, Rebecca Claire Fitzgerald, Janusz Jankowski, Michael Vieth, Andreas Mayr, Puya Gharahkhani, Stuart MacGregor, Ines Gockel, Claire Palles, Johannes Schumacher
doi : 10.1136/gutjnl-2021-326698
Objective Oesophageal cancer (EC) is the sixth leading cause of cancer-related deaths. Oesophageal adenocarcinoma (EA), with Barrett’s oesophagus (BE) as a precursor lesion, is the most prevalent EC subtype in the Western world. This study aims to contribute to better understand the genetic causes of BE/EA by leveraging genome wide association studies (GWAS), genetic correlation analyses and polygenic risk modelling.
Epithelial SOX9 drives progression and metastases of gastric adenocarcinoma by promoting immunosuppressive tumour microenvironment
Yibo Fan, Yuan Li, Xiaodan Yao, Jiangkang Jin, Ailing Scott, Bovey Liu, Shan Wang, Longfei Huo, Ying Wang, Ruiping Wang, Melissa Pool Pizzi, Lang Ma, Shan Shao, Matheus Sewastjanow-Silva, Rebecca Waters, Deyali Chatterjee, Bin Liu, Namita Shanbhag, Guang Peng, George Adrian Calin, Pawel Karol Mazur, Samir M Hanash, Jo Ishizawa, Yuki Hirata, Osamu Nagano, Zhenning Wang, Linghua Wang, Wa Xian, Frank McKeon, Jaffer A Ajani, Shumei Song
doi : 10.1136/gutjnl-2021-326581
Objective Many cancers engage embryonic genes for rapid growth and evading the immune system. SOX9 has been upregulated in many tumours, yet the role of SOX9 in mediating immunosuppressive tumour microenvironment is unclear. Here, we aim to dissect the role of SOX9-mediated cancer stemness attributes and immunosuppressive microenvironment in advanced gastric adenocarcinoma (GAC) for novel therapeutic discoveries.
Use of over-the-scope clip (OTSC) versus standard therapy for the prevention of rebleeding in large peptic ulcers (size ≥1.5 cm): an open-labelled, multicentre international randomised controlled trial
Shannon Chan, Rapat Pittayanon, Hsiu-Po Wang, Jiann-Hwa Chen, Anthony YB Teoh, Yu Ting Kuo, Raymond SY Tang, Hon Chi Yip, Stephen Ka Kei Ng, Sunny Wong, Joyce Wing Yan Mak, Heyson Chan, Louis Lau, Rashid N Lui, Marc Wong, Rungsun Rerknimitr, Enders K Ng, Philip Wai Yan Chiu
doi : 10.1136/gutjnl-2022-327007
Introduction Over-the-scope clip (OTSC) has been used recently for primary haemostasis of peptic ulcers. This study aimed to compare the efficacy of OTSC to standard endoscopic therapy in primary treatment of patients with peptic ulcer bleeding that are of size ≥1.5 cm. The target population accounts for only 2.5% of all upper GI bleeders.
Hypophosphataemia following ferric derisomaltose and ferric carboxymaltose in patients with iron deficiency anaemia due to inflammatory bowel disease (PHOSPHARE-IBD): a randomised clinical trial
Heinz Zoller, Myles Wolf, Irina Blumenstein, Christian Primas, Stefan Lindgren, Lars L Thomsen, Walter Reinisch, Tariq Iqbal
doi : 10.1136/gutjnl-2022-327897
Objective Intravenous iron—a common treatment for anaemia and iron deficiency due to inflammatory bowel disease (IBD)—can cause hypophosphataemia. This trial compared the incidence of hypophosphataemia after treatment with ferric carboxymaltose (FCM) or ferric derisomaltose (FDI).
NOX1 is essential for TNFα-induced intestinal epithelial ROS secretion and inhibits M cell signatures
Nai-Yun Hsu, Shikha Nayar, Kyle Gettler, Sayali Talware, Mamta Giri, Isaac Alter, Carmen Argmann, Ksenija Sabic, Tin Htwe Thin, Huai-Bin Mabel Ko, Robert Werner, Christopher Tastad, Thaddeus Stappenbeck, Aline Azabdaftari, Holm H Uhlig, Ling-Shiang Chuang, Judy H Cho
doi : 10.1136/gutjnl-2021-326305
Objective Loss-of-function mutations in genes generating reactive oxygen species (ROS), such as NOX1, are associated with IBD. Mechanisms whereby loss of ROS drive IBD are incompletely defined.
Antibiotic use as a risk factor for inflammatory bowel disease across the ages: a population-based cohort study
Adam S Faye, Kristine Højgaard Allin, Aske T Iversen, Manasi Agrawal, Jeremiah Faith, Jean-Frederic Colombel, Tine Jess
doi : 10.1136/gutjnl-2022-327845
Background There is an increasing incidence of inflammatory bowel disease (IBD) for which environmental factors are suspected. Antibiotics have been associated with development of IBD in earlier generations, but their influence on IBD risk in adults is uncertain.
Protective and aggressive bacterial subsets and metabolites modify hepatobiliary inflammation and fibrosis in a murine model of PSC
Muyiwa Awoniyi, Jeremy Wang, Billy Ngo, Vik Meadows, Jason Tam, Amba Viswanathan, Yunjia Lai, Stephanie Montgomery, Morgan Farmer, Martin Kummen, Louise Thingholm, Christoph Schramm, Corinna Bang, Andre Franke, Kun Lu, Huiping Zhou, Jasmohan S Bajaj, Phillip B Hylemon, Jenny Ting, Yury V Popov, Johannes Roksund Hov, Heather L Francis, Ryan Balfour Sartor
doi : 10.1136/gutjnl-2021-326500
Objective Conflicting microbiota data exist for primary sclerosing cholangitis (PSC) and experimental models. Goal: define the function of complex resident microbes and their association relevant to PSC patients by studying germ-free (GF) and antibiotic-treated specific pathogen-free (SPF) multidrug-resistant 2 deficient (mdr2−/− ) mice and microbial profiles in PSC patient cohorts.
A novel peptide protects against diet-induced obesity by suppressing appetite and modulating the gut microbiota
Zhanzhan Li, Bing Zhang, Ning Wang, Zhenqiang Zuo, Hong Wei, Fangqing Zhao
doi : 10.1136/gutjnl-2022-328035
Objective The obesity epidemic and its metabolic complications continue to be a major global public health threat with limited effective treatments, especially drugs that can be taken orally. Peptides are a promising class of molecules that have gained increased interest for their applications in medicine and biotechnology. In this study, we focused on looking for peptides that can be administrated orally to treat obesity and exploring its mechanisms.
Autologous T cell responses to primary human colorectal cancer spheroids are enhanced by ectonucleotidase inhibition
Julie Bonnereau, Tristan Courau, Nicolas Asesio, Delphine Salfati, Fatiha Bouhidel, Hélène Corte, Sarah Hamoudi, Nassim Hammoudi, Julie Lavolé, Justine Vivier-Chicoteau, Victor Chardiny, Leon Maggiori, Mathieu Blery, Romain Remark, Cécile Bonnafous, Pierre Cattan, Antoine Toubert, Purnima Bhat, Matthieu Allez, Thomas Aparicio, Lionel Le Bourhis
doi : 10.1136/gutjnl-2021-326553
Objective T cells are major effectors of the antitumoural immune response. Their activation by tumour-associated antigens can unleash their proliferation and cytotoxic functions, leading to tumour cell elimination. However, tumour-related immunosuppressive mechanisms including the overexpression of immune checkpoints like programmed cell death protein-1 (PD-1), are also engaged, promoting immune escape. Current immunotherapies targeting these pathways have demonstrated weak efficacy in colorectal cancer (CRC). It is thus crucial to find new targets for immunotherapy in this cancer type.
Novel TCF21high pericyte subpopulation promotes colorectal cancer metastasis by remodelling perivascular matrix
Xiaobo Li, Jinghua Pan, Tongzheng Liu, Wenqian Yin, Qun Miao, Zhan Zhao, Yufeng Gao, Wei Zheng, Hang Li, Rong Deng, Dandan Huang, Shenghui Qiu, Yiran Zhang, Qi Qi, Lijuan Deng, Maohua Huang, Patrick Ming-Kuen Tang, Yihai Cao, Minfeng Chen, Wencai Ye, Dongmei Zhang
doi : 10.1136/gutjnl-2022-327913
Objective Haematogenous dissemination is a prevalent route of colorectal cancer (CRC) metastasis. However, as the gatekeeper of vessels, the role of tumour pericytes (TPCs) in haematogenous metastasis remains largely unknown. Here, we aimed to investigate the heterogeneity of TPCs and their effects on CRC metastasis.
SK2 channels set a signalling hub bolstering CAF-triggered tumourigenic processes in pancreatic cancer
Raphael Rapetti-Mauss, Jérémy Nigri, Camille Berenguier, Pascal Finetti, Sarah Simha Tubiana, Bonnie Labrum, Benoit Allegrini, Bernard Pellissier, Georgios Efthymiou, Zainab Hussain, Corinne Bousquet, Nelson Dusetti, François Bertucci, Hélène Guizouarn, Patricia Melnyk, Franck Borgese, Richard Tomasini, Olivier Soriani
doi : 10.1136/gutjnl-2021-326610
Objective Intercellular communication within pancreatic ductal adenocarcinoma (PDAC) dramatically contributes to metastatic processes. The underlying mechanisms are poorly understood, resulting in a lack of targeted therapy to counteract stromal-induced cancer cell aggressiveness. Here, we investigated whether ion channels, which remain understudied in cancer biology, contribute to intercellular communication in PDAC.
Novel microenvironment-based classification of intrahepatic cholangiocarcinoma with therapeutic implications
Miguel A Martin-Serrano, Benjamin Kepecs, Miguel Torres-Martin, Emily R Bramel, Philipp K Haber, Elliot Merritt, Alexander Rialdi, Nesteene Joy Param, Miho Maeda, Katherine E Lindblad, James K Carter, Marina Barcena-Varela, Vincenzo Mazzaferro, Myron Schwartz, Silvia Affo, Robert F Schwabe, Augusto Villanueva, Ernesto Guccione, Scott L Friedman, Amaia Lujambio, Anna Tocheva, Josep M Llovet, Swan N Thung, Alexander M Tsankov, Daniela Sia
doi : 10.1136/gutjnl-2021-326514
Objective The diversity of the tumour microenvironment (TME) of intrahepatic cholangiocarcinoma (iCCA) has not been comprehensively assessed. We aimed to generate a novel molecular iCCA classifier that incorporates elements of the stroma, tumour and immune microenvironment (‘STIM’ classification).
Hepatic encephalopathy is not a contraindication to pre-emptive TIPS in high-risk patients with cirrhosis with variceal bleeding
Marika Rudler, Virginia Hernández-Gea, Bogdan Dumitru Procopet, Alvaro Giráldez, Lucio Amitrano, Cà ndid Villanueva, Luis Ibañez, Gilberto Silva-Junior, Joan Genesca, Christophe Bureau, Jonel Trebicka, Rafael Bañares, Aleksander Krag, Elba Llop, Wim Laleman, Jose Maria Palazon, Jose Castellote, Susana Rodrigues, Lise Lotte Gluud, Carlos Noronha Ferreira, Nouria Canete, Manuel RodrÃguez, Arnulf Ferlitsch, Jose Luis Mundi, Henning Gronbaek, Manuel Hernandez-Guerra, Romano Sassatelli, Alessandra Dell’era, Marco Senzolo, Juan G Abraldes, Manuel Romero-Gómez, Alexander Zipprich, Meritxell Casas, Helena Masnou, Hélène Larrue, Massimo Primignani, Frederik Nevens, Jose Luis Calleja, Remy Schwarzer, Christian Jansen, Marie-Angèle Robic, Irene Conejo, Javier MartÃnez Gonzalez, Maria Vega Catalina, AgustÃn Albillos, Edilmar Alvarado, Maria Anna Guardascione, Maxime Mallet, Simona Tripon, Georgina Casanovas, Jaume Bosch, Juan-Carlos Garcia-Pagan, Dominique Thabut
doi : 10.1136/gutjnl-2022-326975
Background A pre-emptive transjugular intrahepatic portosystemic shunt (pTIPS) reduces mortality in high-risk patients with cirrhosis (Child-Pugh C/B+active bleeding) with acute variceal bleeding (AVB). Real-life studies point out that <15% of patients eligible for pTIPS ultimately undergo transjugular intrahepatic portosystemic shunt (TIPS) due to concerns about hepatic encephalopathy (HE). The outcome of patients undergoing pTIPS with HE is unknown. We aimed to (1) assess the prevalence of HE in patients with AVB; (2) evaluate the outcome of patients presenting HE at admission after pTIPS; and (3) determine if HE at admission is a risk factor for death and post-TIPS HE.
Longitudinal transkingdom gut microbial approach towards decompensation in outpatients with cirrhosis
Jasmohan S Bajaj, Marcela Peña-Rodriguez, Alex La Reau, Wendy Phillips, Michael Fuchs, Brian C Davis, Richard K Sterling, Masoumeh Sikaroodi, Andrew Fagan, Amirhossein Shamsaddini, Zachariah Henseler, Tonya Ward, Puneet Puri, Hannah Lee, Patrick M Gillevet
doi : 10.1136/gutjnl-2022-328403
Objective First decompensation development is a critical milestone that needs to be predicted. Transkingdom gut microbial interactions, including archaeal methanogens, may be important targets and predictors but a longitudinal approach is needed.
Microbial transmission, colonisation and succession: from pregnancy to infancy
Liwen Xiao, Fangqing Zhao
doi : 10.1136/gutjnl-2022-328970
The microbiome has been proven to be associated with many diseases and has been used as a biomarker and target in disease prevention and intervention. Currently, the vital role of the microbiome in pregnant women and newborns is increasingly emphasised. In this review, we discuss the interplay of the microbiome and the corresponding immune mechanism between mothers and their offspring during the perinatal period.
Understanding neuroimmune interactions in disorders of gut–brain interaction: from functional to immune-mediated disorders
Tim Vanuytsel, Premysl Bercik, Guy Boeckxstaens
doi : 10.1136/gutjnl-2020-320633
Functional gastrointestinal disorders—recently renamed into disorders of gut–brain interaction—such as irritable bowel syndrome and functional dyspepsia are highly prevalent conditions with bothersome abdominal symptoms in the absence of structural abnormalities.
Serological responses to three doses of SARS-CoV-2 vaccination in inflammatory bowel disease
Joshua Quan, Christopher Ma, Remo Panaccione, Lindsay Hracs, Nastaran Sharifi, Michelle Herauf, Ante Makovinović, Stephanie Coward, Joseph W Windsor, Léa Caplan, Richard J M Ingram, Jamil N Kanji, Graham Tipples, Jessalyn K Holodinsky, Charles N Bernstein, Douglas J Mahoney, Sasha Bernatsky, Eric I Benchimol, Gilaad G Kaplan
Maternal antibiotic exposure during pregnancy and risk of IBD in offspring: a population-based cohort study
Manasi Agrawal, Gry Poulsen, Jean-Frederic Colombel, Kristine Højgaard Allin, Tine Jess
Correspondence on “PICaSSO Histologic Remission Index (PHRI) in ulcerative colitis: development of a novel simplified histological score for monitoring mucosal healing and predicting clinical outcomes and its applicability in an artificial intelligence system� by Gui et al
Emily C L Wong, Parambir S Dulai, Neeraj Narula
Response to: Correspondence on "PICaSSO Histologic Remission Index (PHRI) in ulcerative colitis: development of a novel simplified histological score for monitoring mucosal healing and predicting clinical outcomes and its applicability in an artificial intelligence system" by Wong et al
Marietta Iacucci, Tommaso Lorenzo Parigi, Alina Bazarova, Subrata Ghosh, Vincenzo Villanacci, Xianyong Gui
Great escape: how infectious SARS-CoV-2 avoids inactivation by gastric acidity and intestinal bile
Malak A Esseili
Shaggy white lesion with morphological changes in the oesophagus
Tomoya Ueda, Yohei Yabuuchi, Tetsuro Inokuma
