GI highlights from the literature
Basic scienceMutation signatures in oesophageal adenocarcinoma to direct therapy Secrier M, Li X, de Silva N, et al. Mutational signatures in esophageal adenocarcinoma define etiologically distinct subgroups with therapeutic relevance. Nat Genet 2016;48:1131–41. Recent next-generation sequencing studies have revealed few common mutated driver genes in patients with oesophageal adenocarcinoma (OAC), particularly those with a known history of Barrett's oesophagus. Genomic instability is a feature of these cancers, and altogether these data paint a picture of tremendous genetic heterogeneity, making it difficult to deve...
Source: Gut - December 6, 2016 Category: Gastroenterology Authors: McLean, M. H. Tags: JournalScan Source Type: research

Current and upcoming pharmacotherapy for non-alcoholic fatty liver disease
Given the high prevalence and rising incidence of non-alcoholic fatty liver disease (NAFLD), the absence of approved therapies is striking. Although the mainstay of treatment of NAFLD is weight loss, it is hard to maintain, prompting the need for pharmacotherapy as well. A greater understanding of disease pathogenesis in recent years was followed by development of new classes of medications, as well as potential repurposing of currently available agents. NAFLD therapies target four main pathways. The dominant approach is targeting hepatic fat accumulation and the resultant metabolic stress. Medications in this group includ...
Source: Gut - December 6, 2016 Category: Gastroenterology Authors: Rotman, Y., Sanyal, A. J. Tags: GUT Recent advances in clinical practice, Nonalcoholic steatosis Source Type: research

Epigenetic treatment of pancreatic cancer: is there a therapeutic perspective on the horizon?
Pancreatic ductal adenocarcinoma (PDAC) constitutes one of the most aggressive malignancies with a 5-year survival rate of
Source: Gut - December 6, 2016 Category: Gastroenterology Authors: Hessmann, E., Johnsen, S. A., Siveke, J. T., Ellenrieder, V. Tags: GUT Recent advances in basic science, Pancreas and biliary tract, Open access, Pancreatic cancer Source Type: research

Targeting of tumour-infiltrating macrophages via CCL2/CCR2 signalling as a therapeutic strategy against hepatocellular carcinoma
Conclusions In patients with liver cancer, CCL2 is highly expressed and is a prognostic factor. Blockade of CCL2/CCR2 signalling suppresses murine liver tumour growth via activating T cell antitumour immune response. The results demonstrate the translational potential of CCL2/CCR2 blockade for treatment of HCCs. (Source: Gut)
Source: Gut - December 6, 2016 Category: Gastroenterology Authors: Li, X., Yao, W., Yuan, Y., Chen, P., Li, B., Li, J., Chu, R., Song, H., Xie, D., Jiang, X., Wang, H. Tags: Hepatic cancer Hepatology Source Type: research

Janus-kinase-2 relates directly to portal hypertension and to complications in rodent and human cirrhosis
Conclusions Hepatic JAK2/ARHGEF1/ROCK expression is associated with portal hypertension and decompensation in human cirrhosis. The deletion of Jak2 in myofibroblasts attenuated experimental fibrosis and acute inhibition of JAK2 decreased PP. Thus, JAK2 inhibitors, already in clinical use for other indications, might be a new approach to treat cirrhosis with portal hypertension. (Source: Gut)
Source: Gut - December 6, 2016 Category: Gastroenterology Authors: Klein, S., Rick, J., Lehmann, J., Schierwagen, R., Schierwagen, I. G., Verbeke, L., Hittatiya, K., Uschner, F. E., Manekeller, S., Strassburg, C. P., Wagner, K.-U., Sayeski, P. P., Wolf, D., Laleman, W., Sauerbruch, T., Trebicka, J. Tags: Cirrhosis, Pancreas and biliary tract, Gastrointestinal hormones Hepatology Source Type: research

Myeloid cells are required for PD-1/PD-L1 checkpoint activation and the establishment of an immunosuppressive environment in pancreatic cancer
Conclusion Our results show that myeloid cells support immune evasion in pancreatic cancer through EGFR/MAPK-dependent regulation of PD-L1 expression on tumour cells. Derailing this crosstalk between myeloid cells and tumour cells is sufficient to restore anti-tumour immunity mediated by CD8+ T cells, a finding with implications for the design of immune therapies for pancreatic cancer. (Source: Gut)
Source: Gut - December 6, 2016 Category: Gastroenterology Authors: Zhang, Y., Velez-Delgado, A., Mathew, E., Li, D., Mendez, F. M., Flannagan, K., Rhim, A. D., Simeone, D. M., Beatty, G. L., Pasca di Magliano, M. Tags: Pancreas and biliary tract, Open access, Pancreatic cancer Source Type: research

Attendance and diagnostic yield of repeated two-sample faecal immunochemical test screening for colorectal cancer
Conclusions Using 2-sample FIT instead of 1-sample FIT does not result in a higher detection rate of AN in the second round of repeated FIT screening. Furthermore, both strategies lead to a similar yield of AN over two rounds. These findings imply that 1-sample FIT screening is preferred over 2-sample FIT screening. (Source: Gut)
Source: Gut - December 6, 2016 Category: Gastroenterology Authors: Kapidzic, A., van Roon, A. H. C., van Leerdam, M. E., van Vuuren, A. J., van Ballegooijen, M., Lansdorp-Vogelaar, I., Spijker, W., Izelaar, K., Hol, L., Kuipers, E. J. Tags: Colon cancer Source Type: research

Clinical significance of SNORA42 as an oncogene and a prognostic biomarker in colorectal cancer
Conclusions SNORA42 appears to be a novel oncogene and could serve as a promising predictive biomarker for recurrence and prognosis in patients with CRC. (Source: Gut)
Source: Gut - December 6, 2016 Category: Gastroenterology Authors: Okugawa, Y., Toiyama, Y., Toden, S., Mitoma, H., Nagasaka, T., Tanaka, K., Inoue, Y., Kusunoki, M., Boland, C. R., Goel, A. Tags: Press releases, Colon cancer Source Type: research

Clinicopathological and molecular features of sessile serrated adenomas with dysplasia or carcinoma
Objective Sessile serrated adenomas (SSAs) are the precursors of at least 15% of colorectal carcinomas, but their biology is incompletely understood. We performed a clinicopathological and molecular analysis of a large number of the rarely observed SSAs with dysplasia/carcinoma to better define their features and the pathways by which they progress to carcinoma. Design A cross-sectional analysis of 137 SSAs containing regions of dysplasia/carcinoma prospectively collected at a community GI pathology practice was conducted. Samples were examined for BRAF and KRAS mutations, the CpG island methylator phenotype (CIMP) and im...
Source: Gut - December 6, 2016 Category: Gastroenterology Authors: Bettington, M., Walker, N., Rosty, C., Brown, I., Clouston, A., McKeone, D., Pearson, S.-A., Leggett, B., Whitehall, V. Tags: Colon cancer Source Type: research

High hospital research participation and improved colorectal cancer survival outcomes: a population-based study
Objective In 2001, the National Institute for Health Research Cancer Research Network (NCRN) was established, leading to a rapid increase in clinical research activity across the English NHS. Using colorectal cancer (CRC) as an example, we test the hypothesis that high, sustained hospital-level participation in interventional clinical trials improves outcomes for all patients with CRC managed in those research-intensive hospitals. Design Data for patients diagnosed with CRC in England in 2001–2008 (n=209 968) were linked with data on accrual to NCRN CRC studies (n=30 998). Hospital Trusts were categorised ...
Source: Gut - December 6, 2016 Category: Gastroenterology Authors: Downing, A., Morris, E. J., Corrigan, N., Sebag-Montefiore, D., Finan, P. J., Thomas, J. D., Chapman, M., Hamilton, R., Campbell, H., Cameron, D., Kaplan, R., Parmar, M., Stephens, R., Seymour, M., Gregory, W., Selby, P. Tags: Open access, Colon cancer Source Type: research

A rare cause of colonic thickening and lymphadenopathy
Case A 73-year-old retired analytic chemist presented with 4 weeks of epigastric discomfort, weight loss and loose stools. His medical history revealed pancreatic insufficiency on the background of a pancreatic mass, which had resolved 8 years previously, childhood eczema, and shellfish allergy. Laboratory investigation demonstrated an elevated C-reactive protein of 32 mm/L and IgG of 14.8 g/L with negative endomysial and auto-antibodies, normal blood count, liver function and amylase. CT of the abdomen showed concentric thickening of the ascending colon and caecal wall with serosal abnormality and mesenteri...
Source: Gut - December 6, 2016 Category: Gastroenterology Authors: Culver, E. L., Wang, L. M., Bungay, H., Chapman, R. W., Collier, J. Tags: GUT Snapshot Editor ' s quiz: GI snapshot Source Type: research

Colonic microbiota can promote rapid local improvement of murine colitis by thioguanine independently of T lymphocytes and host metabolism
Conclusions Treatment by TG is not necessarily dependent on the adaptive immune system. TG is a more efficacious treatment than MP in Winnie spontaneous colitis. Rapid local bacterial conversion of TG correlated with decreased intestinal inflammation and immune activation. (Source: Gut)
Source: Gut - December 6, 2016 Category: Gastroenterology Authors: Oancea, I., Movva, R., Das, I., Aguirre de Carcer, D., Schreiber, V., Yang, Y., Purdon, A., Harrington, B., Proctor, M., Wang, R., Sheng, Y., Lobb, M., Lourie, R., O Cuiv, P., Duley, J. A., Begun, J., Florin, T. H. J. Tags: Open access Inflammatory bowel disease Source Type: research

Development and validation of the Nancy histological index for UC
Conclusions A three descriptor histological index has been validated for use in clinical practice and clinical trials. (Source: Gut)
Source: Gut - December 6, 2016 Category: Gastroenterology Authors: Marchal-Bressenot, A., Salleron, J., Boulagnon-Rombi, C., Bastien, C., Cahn, V., Cadiot, G., Diebold, M.-D., Danese, S., Reinisch, W., Schreiber, S., Travis, S., Peyrin-Biroulet, L. Tags: Inflammatory bowel disease Source Type: research

hTERT promotes the invasion of gastric cancer cells by enhancing FOXO3a ubiquitination and subsequent ITGB1 upregulation
Conclusions The hTERT/MDM2–FOXO3a–ITGB1 pathway markedly contributes to hTERT-promoted gastric cancer invasion, suggesting that this pathway might be a novel target for the prevention and treatment of gastric cancer metastasis. (Source: Gut)
Source: Gut - December 6, 2016 Category: Gastroenterology Authors: Hu, C., Ni, Z., Li, B.-s., Yong, X., Yang, X., Zhang, J.-w., Zhang, D., Qin, Y., Jie, M.-m., Dong, H., Li, S., He, F., Yang, S.-m. Tags: Pancreatic cancer Stomach Source Type: research

Anti-GP2 IgA: a biomarker for disease severity and/or cholangiocarcinoma in primary sclerosing cholangitis?
Primary sclerosing cholangitis (PSC) is a heterogeneous and complex syndrome with highly variable disease progression and unknown etiopathogenesis, the latter perhaps influenced by the microbiome.1 2 Moreover, it is a premalignant disease in that it confers a significant risk for the development of cholangiocarcinoma (CCA) in a subset of patients.3 Detection of CCA in PSC poses a major diagnostic dilemma as inflammation-related dominant strictures in PSC may mimic malignant strictures.3 Contemporary diagnostic modalities for early detection of CCA in patients with PSC remain suboptimal although innovative approaches are em...
Source: Gut - December 6, 2016 Category: Gastroenterology Authors: Rizvi, S., Yang, J. D., Gores, G. J. Tags: Commentaries Source Type: research

Refined strategies for the treatment of pancreatic carcinoma: targeting myeloid cells in order to overcome T cell exhaustion
Cancer creates an environment of constant antigen exposure and inflammation. In this setting, T cells transform into a differentiation state that has been termed T cell exhaustion, which is characterised by upregulation of inhibitory receptors, like TIM-3 and PD-1, resulting in loss of effector function. The discovery of receptor-mediated immune checkpoints, which prevent uncontrolled T cell reactions, led to the development of a new class of antibodies termed checkpoint inhibitors, bringing exhaustion phenomena to the forefront of tumour research. Data on the efficacy of checkpoint inhibitors in pancreatic cancer are stil...
Source: Gut - December 6, 2016 Category: Gastroenterology Authors: Bauer, C. Tags: Commentaries Source Type: research

Microbiota: relevant player in thiopurine metabolisation?
In this issue, Oancea et al1 demonstrate for the first time that gut microbiota is able to convert the thiopurine drug thioguanine into therapeutically active thiopurine nucleotides (TGN). They thereby open new perspectives for an optimised use of thiopurines in the treatment of patients with IBD and inspire the vision of topical thiopurine delivery to the inflamed gut. During the last years, our understanding of the molecular mechanisms, which underlie the well-known efficacy of thiopurines in IBD therapy, has been improved significantly. In order to allow potent therapeutic effects, classic thiopurine drugs including aza...
Source: Gut - December 6, 2016 Category: Gastroenterology Authors: Atreya, I., Neurath, M. F. Tags: Commentaries Source Type: research

GI highlights from the literature
In this study, the authors have identified a key role for integrin-ß1 in myofibroblasts, signalling via the mechanosensitive transcriptional coactivator factor yes-associated protein 1... (Source: Gut)
Source: Gut - November 8, 2016 Category: Gastroenterology Authors: McLean, M. H. Tags: JournalScan Source Type: research

Erratum: Daclatasvir plus sofosbuvir, with or without ribavirin, achieved high sustained virological response rates in patients with HCV infection and advanced liver disease in a real-world cohort
Welzel TM, Petersen J, Herzer K, et al. Daclatasvir plus sofosbuvir, with or without ribavirin, achieved high sustained virological response rates in patients with HCV infection and advanced liver disease in a real-world cohort. Gut 2016;65:1861–70. The trial registration number has been corrected to NCT02097966. (Source: Gut)
Source: Gut - November 8, 2016 Category: Gastroenterology Tags: Correction Source Type: research

Expert opinions and scientific evidence for colonoscopy key performance indicators
Colonoscopy is a widely performed procedure with procedural volumes increasing annually throughout the world. Many procedures are now performed as part of colorectal cancer screening programmes. Colonoscopy should be of high quality and measures of this quality should be evidence based. New UK key performance indicators and quality assurance standards have been developed by a working group with consensus agreement on each standard reached. This paper reviews the scientific basis for each of the quality measures published in the UK standards. (Source: Gut)
Source: Gut - November 8, 2016 Category: Gastroenterology Authors: Rees, C. J., Bevan, R., Zimmermann-Fraedrich, K., Rutter, M. D., Rex, D., Dekker, E., Ponchon, T., Bretthauer, M., Regula, J., Saunders, B., Hassan, C., Bourke, M. J., Rösch, T. Tags: Endoscopy, GUT Recent advances in clinical practice, Open access, Colon cancer Source Type: research

Gut microbiome and liver diseases
The gut microbiota has recently evolved as a new important player in the pathophysiology of many intestinal and extraintestinal diseases. The liver is the organ which is in closest contact with the intestinal tract, and is exposed to a substantial amount of bacterial components and metabolites. Various liver disorders such as alcoholic liver disease, non-alcoholic liver disease and primary sclerosing cholangitis have been associated with an altered microbiome. This dysbiosis may influence the degree of hepatic steatosis, inflammation and fibrosis through multiple interactions with the host's immune system and other cell ty...
Source: Gut - November 8, 2016 Category: Gastroenterology Authors: Tilg, H., Cani, P. D., Mayer, E. A. Tags: GUT Recent advances in basic science, Alcoholic liver disease, Cirrhosis, Pancreas and biliary tract, Editor's choice Source Type: research

Host cell mTORC1 is required for HCV RNA replication
Conclusions Our data identify mTORC1 as a novel HCV replication factor. These findings suggest an underlying mechanism for the observed benefits of mTOR inhibition in HCV-positive OLT recipients and potentiate further investigation of mTOR-containing regimens in HCV-positive recipients of solid organ transplants. (Source: Gut)
Source: Gut - November 8, 2016 Category: Gastroenterology Authors: Stöhr, S., Costa, R., Sandmann, L., Westhaus, S., Pfaender, S., Anggakusuma, , Dazert, E., Meuleman, P., Vondran, F. W. R., Manns, M. P., Steinmann, E., von Hahn, T., Ciesek, S. Tags: Open access Hepatology Source Type: research

Natural history of chronic HBV infection in West Africa: a longitudinal population-based study from The Gambia
Conclusions The incidence of HCC among chronic HBV carriers in West Africa was higher than that in Europe but lower than rates in East Asia. High risk of severe liver disease among the few who are infected by their mothers underlines the importance of interrupting perinatal transmission in sub-Saharan Africa. (Source: Gut)
Source: Gut - November 8, 2016 Category: Gastroenterology Authors: Shimakawa, Y., Lemoine, M., Njai, H. F., Bottomley, C., Ndow, G., Goldin, R. D., Jatta, A., Jeng-Barry, A., Wegmuller, R., Moore, S. E., Baldeh, I., Taal, M., D'Alessandro, U., Whittle, H., Njie, R., Thursz, M., Mendy, M. Tags: Cirrhosis, Hepatic cancer Hepatology Source Type: research

Lack of Siglec-7 expression identifies a dysfunctional natural killer cell subset associated with liver inflammation and fibrosis in chronic HCV infection
Conclusions These findings identify Siglec-7neg NK cells as a dysfunctional subpopulation associated with severe liver disease in chronic HCV infection. (Source: Gut)
Source: Gut - November 8, 2016 Category: Gastroenterology Authors: Varchetta, S., Mele, D., Lombardi, A., Oliviero, B., Mantovani, S., Tinelli, C., Spreafico, M., Prati, D., Ludovisi, S., Ferraioli, G., Filice, C., Aghemo, A., Lampertico, P., Facchetti, F., Bernuzzi, F., Invernizzi, P., Mondelli, M. U. Tags: Hepatology Source Type: research

HVR1-mediated antibody evasion of highly infectious in vivo adapted HCV in humanised mice
Conclusions The A876P-substitution bridges in vitro and in vivo studies using J6/JFH1-based recombinants. We provide the first in vivo evidence that HVR1 protects cross-genotype conserved HCV neutralisation epitopes, which advocates the possibility of using HVR1-deleted viruses as vaccine antigens to boost broadly reactive protective nAb responses. (Source: Gut)
Source: Gut - November 8, 2016 Category: Gastroenterology Authors: Prentoe, J., Verhoye, L., Velazquez Moctezuma, R., Buysschaert, C., Farhoudi, A., Wang, R., Alter, H., Meuleman, P., Bukh, J. Tags: Open access Hepatology Source Type: research

Identifying the 'Right colon lesion
A 64-year-old woman presented to the colorectal clinic with 3 months of symptoms of loose stools, flatulence and some weight loss. There was no history of abdominal pain, rectal bleeding or anaemia. A similar episode 5 years earlier resolved spontaneously but was investigated with a colonoscopy at that time and revealed diverticular disease and a 3 mm hyperplastic polyp at the hepatic flexure. To investigate the current symptoms, a repeat colonoscopy was advised but this was initially declined in favour of CT colonography (CTC) to avoid the laxative preparation and pain experienced during the previous examin...
Source: Gut - November 8, 2016 Category: Gastroenterology Authors: Hopper, A. D., Mooney, P. D., Blakeborough, A. Tags: GUT Snapshot Editor ' s quiz: GI snapshot Source Type: research

Biomarkers for bile acid diarrhoea in functional bowel disorder with diarrhoea: a systematic review and meta-analysis
There is no universally available laboratory test to diagnose bile acid diarrhoea (BAD). Objective To conduct a systematic review and meta-analysis to identify a biomarker for idiopathic BAD in patients with functional bowel disorder (FBD) with diarrhoea. Design We searched multiple databases through 15 May 2015. Data were only available to estimate the diagnostic yield of each test (the prevalence of a positive test). Estimates were pooled across studies using the random effects model. Results We included 36 studies, enrolling 5028 patients (24 using 75selenium homotaurocholic acid test (75SeHCAT) retention of
Source: Gut - November 8, 2016 Category: Gastroenterology Authors: Valentin, N., Camilleri, M., Altayar, O., Vijayvargiya, P., Acosta, A., Nelson, A. D., Murad, M. H. Tags: Diarrhoea Neurogastroenterology Source Type: research

miR-301a promotes intestinal mucosal inflammation through induction of IL-17A and TNF-{alpha} in IBD
Conclusions Our data reveal a novel mechanism in which the elevated miR-301a in PBMC and inflamed mucosa of IBD promotes Th17 cell differentiation through downregulation of SNIP1. Blockade of miR-301a in vivo may serve as a novel therapeutic approach in the treatment of IBD. (Source: Gut)
Source: Gut - November 8, 2016 Category: Gastroenterology Authors: He, C., Shi, Y., Wu, R., Sun, M., Fang, L., Wu, W., Liu, C., Tang, M., Li, Z., Wang, P., Cong, Y., Liu, Z. Tags: Inflammatory bowel disease Source Type: research

Intestinal cell damage and systemic immune activation in individuals reporting sensitivity to wheat in the absence of coeliac disease
Conclusions These findings reveal a state of systemic immune activation in conjunction with a compromised intestinal epithelium affecting a subset of individuals who experience sensitivity to wheat in the absence of coeliac disease. (Source: Gut)
Source: Gut - November 8, 2016 Category: Gastroenterology Authors: Uhde, M., Ajamian, M., Caio, G., De Giorgio, R., Indart, A., Green, P. H., Verna, E. C., Volta, U., Alaedini, A. Tags: Open access, Coeliac disease Small bowel Source Type: research

Non-coeliac gluten sensitivity: are we closer to separating the wheat from the chaff?
There is growing interest in the role of food as a trigger of functional bowel disorders such as IBS. Indeed, more than 60% of patients with IBS relate the occurrence of bloating and abdominal pain after the ingestion of certain foods.1 Despite intense research in the area, the identification of specific food triggers has remained elusive and this has hampered our understanding of the underlying pathophysiology of these conditions. One clinical entity that embodies the complex relationship between food and gut functional symptoms is non-coeliac gluten sensitivity or non-coeliac wheat sensitivity (NCGS/NCWS) (figure 1). The...
Source: Gut - November 8, 2016 Category: Gastroenterology Authors: Pinto-Sanchez, M. I., Verdu, E. F. Tags: Commentary Source Type: research

A practical guide to assess the Nancy histological index for UC
Recently, we published the first validated index to assess histological disease activity in UC.1 We believe that some clarifications have to be made regarding the assessment of this index in both clinical practice and clinical trials. Three histological criteria have to be assessed. The first criterion is the presence of mucosal ulceration defined by the loss of colonic crypts replaced with ‘immature’ granulation tissue (defined as disorganised blood vessels with extravasated neutrophils) or the presence of fibrinopurulent exudate. The presence of only epithelial stripping should not be considered as ulceration...
Source: Gut - October 6, 2016 Category: Gastroenterology Authors: Marchal-Bressenot, A., Scherl, A., Salleron, J., Peyrin-Biroulet, L. Tags: Open access PostScript Source Type: research

Brexit from current guideline recommendations?
Dear Editor, We appreciate the interest of O'Brien et al in our position paper recently published in Gut.1 O'Brien et al raised a very important question: is human serum albumin (HSA) the best resuscitation fluid in patients with cirrhosis and acute kidney injury (AKI)? In our minds, as in that of almost all experts in this field, the answer is absolutely yes. This certainty is based on several clinical and experimental evidences and cannot be challenged by studies performed in critically ill patients that are inconsistent for this purpose considering (a) the low percentage of patients with cirrhosis who were included and ...
Source: Gut - October 6, 2016 Category: Gastroenterology Authors: Angeli, P., Piano, S., Arroyo, V., on behalf of the International Club of Ascites Tags: PostScript Source Type: research

GI highlights from the literature
Basic scienceNovel experimental model of colorectal cancer tumourigenesis Chen HJ, Wei Z, Sun J, et al. A recellularized human colon model identifies cancer driver genes. Nat Biotechnol 2016;34:845–51. Modelling human colonic cancer is challenging. Cell lines, organoids and animal models provide some understanding, but they all have major flaws. This recent paper has described a model of the human colon using recellularised matrix colonised with other native cells to reconstruct the colon and maintain it in viable culture for long enough to perform meaningful experiments. The process of recellularisation began with t...
Source: Gut - October 6, 2016 Category: Gastroenterology Authors: McLean, M. H. Tags: JournalScan Source Type: research

Antibiotics as deep modulators of gut microbiota: between good and evil
The recent increase in our knowledge of human gut microbiota has changed our view on antibiotics. Antibiotics are, indeed, no longer considered only beneficial, but also potentially harmful drugs, as their abuse appears to play a role in the pathogenesis of several disorders associated with microbiota impairment (eg, Clostridium difficile infection or metabolic disorders). Both drug-related factors (such as antibiotic class, timing of exposure or route of administration) and host-related factors appear to influence the alterations of human gut microbiota produced by antibiotics. Nevertheless, antibiotics are nowadays consi...
Source: Gut - October 6, 2016 Category: Gastroenterology Authors: Ianiro, G., Tilg, H., Gasbarrini, A. Tags: Clostridium difficile, GUT Recent advances in basic science, GUT Recent advances in clinical practice, Editor's choice Source Type: research

Epigenetics in liver disease: from biology to therapeutics
Knowledge of the fundamental epigenetic mechanisms governing gene expression and cellular phenotype are sufficiently advanced that novel insights into the epigenetic control of chronic liver disease are now emerging. Hepatologists are in the process of shedding light on the roles played by DNA methylation, histone/chromatin modifications and non-coding RNAs in specific liver pathologies. Alongside these discoveries are advances in the technologies for the detection and quantification of epigenetic biomarkers, either directly from patient tissue or from body fluids. The premise for this review is to survey the recent advanc...
Source: Gut - October 6, 2016 Category: Gastroenterology Authors: Hardy, T., Mann, D. A. Tags: GUT Recent advances in basic science, Nonalcoholic steatosis, Open access, Hepatic cancer Source Type: research

Liver microRNA-21 is overexpressed in non-alcoholic steatohepatitis and contributes to the disease in experimental models by inhibiting PPAR{alpha} expression
Conclusions MicroRNA-21 inhibition or suppression decreases liver injury, inflammation and fibrosis, by restoring PPARα expression. Antagomir-21 might be a future therapeutic strategy for NASH. (Source: Gut)
Source: Gut - October 6, 2016 Category: Gastroenterology Authors: Loyer, X., Paradis, V., Henique, C., Vion, A.-C., Colnot, N., Guerin, C. L., Devue, C., On, S., Scetbun, J., Romain, M., Paul, J.-L., Rothenberg, M. E., Marcellin, P., Durand, F., Bedossa, P., Prip-Buus, C., Bauge, E., Staels, B., Boulanger, C. M., Tedgui Tags: Open access Hepatology Source Type: research

Stress-activated miR-21/miR-21* in hepatocytes promotes lipid and glucose metabolic disorders associated with high-fat diet consumption
Conclusions Hepatic miR-21/miR-21* deficiency prevents glucose intolerance and steatosis in mice fed an obesogenic diet by altering the expression of several master metabolic regulators. This study points out miR-21/miR-21* as a potential therapeutic target for non-alcoholic fatty liver disease and the metabolic syndrome. (Source: Gut)
Source: Gut - October 6, 2016 Category: Gastroenterology Authors: Calo, N., Ramadori, P., Sobolewski, C., Romero, Y., Maeder, C., Fournier, M., Rantakari, P., Zhang, F.-P., Poutanen, M., Dufour, J.-F., Humar, B., Nef, S., Foti, M. Tags: Nonalcoholic steatosis, Hepatic cancer Hepatology Source Type: research

Daclatasvir plus sofosbuvir, with or without ribavirin, achieved high sustained virological response rates in patients with HCV infection and advanced liver disease in a real-world cohort
Conclusions DCV+SOF with or without RBV achieved high SVR12 and was well tolerated in a diverse cohort of patients with severe liver disease. Trial registration number NCT0209966. (Source: Gut)
Source: Gut - October 6, 2016 Category: Gastroenterology Authors: Welzel, T. M., Petersen, J., Herzer, K., Ferenci, P., Gschwantler, M., Wedemeyer, H., Berg, T., Spengler, U., Weiland, O., van der Valk, M., Rockstroh, J., Peck-Radosavljevic, M., Zhao, Y., Jimenez-Exposito, M. J., Zeuzem, S. Tags: Open access Hepatology Source Type: research

MicroRNA-21 is a potential link between non-alcoholic fatty liver disease and hepatocellular carcinoma via modulation of the HBP1-p53-Srebp1c pathway
Conclusions Our findings reveal a novel mechanism by which microRNA-21, in part, promotes hepatic lipid accumulation and cancer progression by interacting with the Hbp1-p53-Srebp1c pathway and suggest the potential therapeutic value of microRNA-21-ASO for both disorders. (Source: Gut)
Source: Gut - October 6, 2016 Category: Gastroenterology Authors: Wu, H., Ng, R., Chen, X., Steer, C. J., Song, G. Tags: Nonalcoholic steatosis, Open access, Hepatic cancer Hepatology Source Type: research

Tumour-specific delivery of siRNA-coupled superparamagnetic iron oxide nanoparticles, targeted against PLK1, stops progression of pancreatic cancer
Conclusions Our data suggest siPLK1-StAv-SPIONs with dual specificity residues for tumour targeting and membrane translocation to represent an exciting opportunity for targeted therapy in patients with PDAC. (Source: Gut)
Source: Gut - October 6, 2016 Category: Gastroenterology Authors: Mahajan, U. M., Teller, S., Sendler, M., Palankar, R., van den Brandt, C., Schwaiger, T., Kühn, J.-P., Ribback, S., Glöckl, G., Evert, M., Weitschies, W., Hosten, N., Dombrowski, F., Delcea, M., Weiss, F.-U., Lerch, M. M., Mayerle, J. Tags: Pancreas and biliary tract, Open access, Pancreatic cancer Source Type: research

Colorectal cancer risk factors in patients with serrated polyposis syndrome: a large multicentre study
Conclusions Patients with SPS have an increased risk of CRC, although lower than previously published. Close colonoscopy surveillance in experienced centres show a low risk of developing CRC (1.9% in 5 years). Specific polyp features (SSA/P histology, proximal location and presence of high-grade dysplasia) should be used to guide clinical management. (Source: Gut)
Source: Gut - October 6, 2016 Category: Gastroenterology Authors: Carballal, S., Rodriguez-Alcalde, D., Moreira, L., Hernandez, L., Rodriguez, L., Rodriguez-Moranta, F., Gonzalo, V., Bujanda, L., Bessa, X., Poves, C., Cubiella, J., Castro, I., Gonzalez, M., Moya, E., Oquinena, S., Clofent, J., Quintero, E., Esteban, P., Tags: Endoscopy, Colon cancer Source Type: research

Appropriateness of endoscopic surveillance recommendations in organised colorectal cancer screening programmes based on the faecal immunochemical test
Conclusions In organised screening programmes, a high rate of inappropriate recommendations for patients with low risk or no adenomas occurs, affecting the demand for endoscopic surveillance by a third. (Source: Gut)
Source: Gut - October 6, 2016 Category: Gastroenterology Authors: Zorzi, M., Senore, C., Turrin, A., Mantellini, P., Visioli, C. B., Naldoni, C., Sassoli de Bianchi, P., Fedato, C., Anghinoni, E., Zappa, M., Hassan, C., the Italian colorectal cancer screening survey group, Giacomo, Sigillito, Rizzo, Luciano, Coppola, Ba Tags: Endoscopy, Colon cancer Source Type: research

High-level adherence to a Mediterranean diet beneficially impacts the gut microbiota and associated metabolome
Conclusions High-level consumption of plant foodstuffs consistent with an MD is associated with beneficial microbiome-related metabolomic profiles in subjects ostensibly consuming a Western diet. Trial registration number This study was registered at clinical trials.gov as NCT02118857. (Source: Gut)
Source: Gut - October 6, 2016 Category: Gastroenterology Authors: De Filippis, F., Pellegrini, N., Vannini, L., Jeffery, I. B., La Storia, A., Laghi, L., Serrazanetti, D. I., Di Cagno, R., Ferrocino, I., Lazzi, C., Turroni, S., Cocolin, L., Brigidi, P., Neviani, E., Gobbetti, M., O'Toole, P. W., Ercolini, D. Tags: Gut microbiota Source Type: research

A TPL2 (MAP3K8) disease-risk polymorphism increases TPL2 expression thereby leading to increased pattern recognition receptor-initiated caspase-1 and caspase-8 activation, signalling and cytokine secretion
Conclusions Taken together, the rs1042058 GG IBD-risk polymorphism in TPL2 results in a gain-of-function by increasing TPL2 expression and signalling, thereby amplifying PRR-initiated outcomes. (Source: Gut)
Source: Gut - October 6, 2016 Category: Gastroenterology Authors: Hedl, M., Abraham, C. Tags: Crohn's disease Inflammatory bowel disease Source Type: research

Heritability of non-HLA genetics in coeliac disease: a population-based study in 107 000 twins
Conclusions CD is characterised by a high heritability, but our study also suggests that non-shared environmental factors may be of importance to CD development. HLA seems to have only moderate impact on heritability estimates. (Source: Gut)
Source: Gut - October 6, 2016 Category: Gastroenterology Authors: Kuja-Halkola, R., Lebwohl, B., Halfvarson, J., Wijmenga, C., Magnusson, P. K. E., Ludvigsson, J. F. Tags: Coeliac disease Source Type: research

A rare cause of GI bleeding in a patient with cutaneous vascular malformations
Clinical presentation A 53-year-old woman with a background of chronic bronchitis was admitted with an infective exacerbation of chronic obstructive pulmonary disease. Her medical history included atrial septal defect (ASD) and ventricular septal defect (VSD) repair in childhood and a recent deep vein thrombosis, for which she was on rivaroxaban. On examination, she had multiple blue pigmented soft tissue lesions on her face, tongue, torso and hands (figures 1 and 2). During her admission, the patient developed melaena associated with a significant acute drop in her haemoglobin (Hb). She was treated with prothrombin comple...
Source: Gut - October 6, 2016 Category: Gastroenterology Authors: Tsoutsouki, J., Laskaratos, F.-M., Mason, S., Smith, M., Sinha, L. Tags: GUT Snapshot Editor ' s quiz: GI snapshot Source Type: research

Sequential therapy for 10 days versus triple therapy for 14 days in the eradication of Helicobacter pylori in the community and hospital populations: a randomised trial
Conclusions S10 was not superior to T14 in areas with low clarithromycin resistance. Trial registration number NCT01607918. (Source: Gut)
Source: Gut - October 6, 2016 Category: Gastroenterology Authors: Liou, J.-M., Chen, C.-C., Chang, C.-Y., Chen, M.-J., Chen, C.-C., Fang, Y.-J., Lee, J.-Y., Yang, T.-H., Luo, J.-C., Wu, J.-Y., Liou, T.-C., Chang, W.-H., Hsu, Y.-C., Tseng, C.-H., Chang, C.-C., Bair, M.-J., Liu, T.-Y., Hsieh, C.-F., Tsao, F.-Y., Shun, C.- Tags: Open access Helicobacter pylori Source Type: research

Emerging role of miR-21 in non-alcoholic fatty liver disease
Non-alcoholic fatty liver disease (NAFLD) has recently been linked to hepatocellular carcinoma (HCC) development, with or without the presence of cirrhosis, both in human disease and animal models. NAFLD is the hepatic manifestation of the metabolic syndrome associated with obesity, hyperinsulinaemia, type 2 diabetes, insulin resistance, hypertriglyceridaemia and hypertension, affecting up to one-third of the population worldwide.1 The diagnosis is related to the presence of excess liver droplets accumulation that can progress from hepatic steatosis to inflammation-associated steatohepatitis (non-alcoholic steatohepatitis,...
Source: Gut - October 6, 2016 Category: Gastroenterology Authors: Benhamouche-Trouillet, S., Postic, C. Tags: Commentary Source Type: research

siRNA-coupled nanoparticles for improved therapeutic targeting of pancreatic cancer
Pancreatic cancer (PC) is one of the most lethal malignancies, characterised by a poor response to conventional chemotherapy and rapid development of secondary resistances. Compared with most other digestive tract cancers, progress in PC treatment has been miniscule over the past decades. The most frequently mutated genes, KRAS and p53, are still difficult to target, and so far only EGFR inhibition (erlotinib) is routinely used in clinical practice for targeted therapy. PC treatment is further complicated by a dense tumour stroma and low vessel density, leading to impaired drug delivery and high adverse effects of systemic...
Source: Gut - October 6, 2016 Category: Gastroenterology Authors: Lange, S., Saur, D., Rad, R. Tags: Commentary Source Type: research

The influence of heredity versus environment on coeliac disease
For coeliac disease (CD) to manifest itself, certain common gene variants within the human leucocyte antigen (HLA) complex must be present. These HLA gene variants are necessary but not sufficient for the disease to develop, as both environmental factors and other gene variants play their role in CD. In order to determine the effect of environmental factors versus genetic factors in disease development, studies are conducted using twins. One such study of Italian twins suggests that very little of the risk of developing CD is due to environmental factors. In fact, the study indicates that CD is influenced by an unusually s...
Source: Gut - October 6, 2016 Category: Gastroenterology Authors: Torinsson Naluai, A. Tags: Commentary Source Type: research