Epigenetic modification of MiR-429 promotes liver tumour-initiating cell properties by targeting Rb binding protein 4
Conclusions Epigenetic modification of miR-429 can manipulate liver T-ICs by targeting the RBBP4/E2F1/OCT4 axis. This miRNA might be targeted to inactivate T-ICs, thus providing a novel strategy for HCC prevention and treatment. (Source: Gut)
Source: Gut - December 8, 2014 Category: Gastroenterology Authors: Li, L., Tang, J., Zhang, B., Yang, W., LiuGao, M., Wang, R., Tan, Y., Fan, J., Chang, Y., Fu, J., Jiang, F., Chen, C., Yang, Y., Gu, J., Wu, D., Guo, L., Cao, D., Li, H., Cao, G., Wu, M., Zhang, M. Q., Chen, L., Wang, H. Tags: Hepatic cancer Hepatology Source Type: research

Functional analysis of ABCB4 mutations relates clinical outcomes of progressive familial intrahepatic cholestasis type 3 to the degree of MDR3 floppase activity
Conclusions These data provide experimental evidence of the correlation between the degree of MDR3 floppase activity and the clinical outcomes of PFIC3. (Source: Gut)
Source: Gut - December 8, 2014 Category: Gastroenterology Authors: Gordo-Gilart, R., Andueza, S., Hierro, L., Martinez-Fernandez, P., D'Agostino, D., Jara, P., Alvarez, L. Tags: Pancreas and biliary tract Hepatology Source Type: research

Anti-HBV DNA vaccination does not prevent relapse after discontinuation of analogues in the treatment of chronic hepatitis B: a randomised trial--ANRS HB02 VAC-ADN
Objective The antiviral efficacy of nucleos(t)ide analogues whose main limitation is relapse after discontinuation requires long-term therapy. To overcome the risk of relapse and virological breakthrough during long-term therapy, we performed a phase I/II, open, prospective, multicentre trial using a HBV envelope-expressing DNA vaccine. Design 70 patients treated effectively with nucleos(t)ide analogues for a median of 3 years (HBV DNA
Source: Gut - December 8, 2014 Category: Gastroenterology Authors: Fontaine, H., Kahi, S., Chazallon, C., Bourgine, M., Varaut, A., Buffet, C., Godon, O., Meritet, J. F., Saidi, Y., Michel, M. L., Scott-Algara, D., Aboulker, J. P., Pol, S., for the ANRS HB02 study group Tags: Hepatology Source Type: research

Simvastatin is associated with reduced risk of acute pancreatitis: findings from a regional integrated healthcare system
Objective To characterise the relationship between simvastatin and risk of acute pancreatitis (AP). Design We conducted a retrospective cohort study (2006–2012) on data from an integrated healthcare system in southern California. Exposure to simvastatin was calculated from time of initial dispensation until 60 days following prescription termination. AP cases were defined by ICD-9 CM 577.0 and serum lipase≥3 times normal. Patients were censored at death, last follow-up, and onset of AP or end-of-study. Incidence rate of pancreatitis among simvastatin users was compared with the adult reference population. Ro...
Source: Gut - December 8, 2014 Category: Gastroenterology Authors: Wu, B. U., Pandol, S. J., Liu, I.-L. A. Tags: Pancreas and biliary tract, Pancreatitis Source Type: research

An updated Asia Pacific Consensus Recommendations on colorectal cancer screening
Conclusions Based on recent data on CRC screening, an updated list of recommendations on CRC screening is prepared. These consensus statements will further enhance the implementation of CRC screening in the Asia Pacific region. (Source: Gut)
Source: Gut - December 8, 2014 Category: Gastroenterology Authors: Sung, J. J. Y., Ng, S. C., Chan, F. K. L., Chiu, H. M., Kim, H. S., Matsuda, T., Ng, S. S. M., Lau, J. Y. W., Zheng, S., Adler, S., Reddy, N., Yeoh, K. G., Tsoi, K. K. F., Ching, J. Y. L., Kuipers, E. J., Rabeneck, L., Young, G. P., Steele, R. J., Lieberm Tags: Endoscopy, Colon cancer Source Type: research

A candidate gene study of capecitabine-related toxicity in colorectal cancer identifies new toxicity variants at DPYD and a putative role for ENOSF1 rather than TYMS
Conclusions DPYD harbours rare and common capecitabine toxicity variants. The toxicity polymorphism in the TYMS region may actually act through ENOSF1. (Source: Gut)
Source: Gut - December 8, 2014 Category: Gastroenterology Authors: Rosmarin, D., Palles, C., Pagnamenta, A., Kaur, K., Pita, G., Martin, M., Domingo, E., Jones, A., Howarth, K., Freeman-Mills, L., Johnstone, E., Wang, H., Love, S., Scudder, C., Julier, P., Fernandez-Rozadilla, C., Ruiz-Ponte, C., Carracedo, A., Castellvi Tags: Open access, Colon cancer Source Type: research

Role of tumour molecular and pathology features to estimate colorectal cancer risk for first-degree relatives
Conclusions Molecular pathology features are potentially useful to refine screening recommendations for first-degree relatives of CRC cases and to identify which cases are more likely to be caused by genetic or other familial factors. (Source: Gut)
Source: Gut - December 8, 2014 Category: Gastroenterology Authors: Win, A. K., Buchanan, D. D., Rosty, C., MacInnis, R. J., Dowty, J. G., Dite, G. S., Giles, G. G., Southey, M. C., Young, J. P., Clendenning, M., Walsh, M. D., Walters, R. J., Boussioutas, A., Smyrk, T. C., Thibodeau, S. N., Baron, J. A., Potter, J. D., Ne Tags: Colon cancer Source Type: research

Diets that differ in their FODMAP content alter the colonic luminal microenvironment
Objective A low FODMAP (Fermentable Oligosaccharides, Disaccharides, Monosaccharides And Polyols) diet reduces symptoms of IBS, but reduction of potential prebiotic and fermentative effects might adversely affect the colonic microenvironment. The effects of a low FODMAP diet with a typical Australian diet on biomarkers of colonic health were compared in a single-blinded, randomised, cross-over trial. Design Twenty-seven IBS and six healthy subjects were randomly allocated one of two 21-day provided diets, differing only in FODMAP content (mean (95% CI) low 3.05 (1.86 to 4.25) g/day vs Australian 23.7 (16.9 to 30.6) g/day)...
Source: Gut - December 8, 2014 Category: Gastroenterology Authors: Halmos, E. P., Christophersen, C. T., Bird, A. R., Shepherd, S. J., Gibson, P. R., Muir, J. G. Tags: Gut microbiota Source Type: research

Increased colonic bile acid exposure: a relevant factor for symptoms and treatment in IBS
Objective Bile acids may play a role in the pathogenesis of IBS. We investigated the potential effects of bile acids entering the colon and its role in the symptom pattern in IBS. Design We measured 75Se-labelled homocholic acid-taurine (75SeHCAT) retention, and serum levels of 7α-hydroxy-4-cholesten-3-one (C4) and fibroblast growth factor (FGF) 19 in patients with IBS (n=141) and control subjects (75SeHCAT n=29; C4 and FGF19 n=435). In patients with IBS stool frequency and form, as well as GI symptom severity were registered, and in a proportion of patients colonic transit time and rectal sensitivity were measured ...
Source: Gut - December 8, 2014 Category: Gastroenterology Authors: Bajor, A., Tornblom, H., Rudling, M., Ung, K.-A., Simren, M. Tags: Neurogastroenterology Source Type: research

Vedolizumab affects antibody responses to immunisation selectively in the gastrointestinal tract: randomised controlled trial results
Conclusions Vedolizumab did not alter the response to parenterally administered antigens but reduced the response to oral antigens, demonstrating its gut-selective mechanism of action. Trial registration number NCT Number: 01981616; EudraCT Number: 2011-001874-24. (Source: Gut)
Source: Gut - December 8, 2014 Category: Gastroenterology Authors: Wyant, T., Leach, T., Sankoh, S., Wang, Y., Paolino, J., Pasetti, M. F., Feagan, B. G., Parikh, A. Tags: Inflammatory bowel disease Source Type: research

XIAP variants in male Crohn's disease
Conclusions This study reveals the unanticipated, frequent occurrence of XIAP variants in male paediatric-onset CD. The link between XIAP and NOD1/2, and the association of XIAP variants with XLP2, support the concept of PID in a subset of IBD patients. Moreover, these studies provide a rationale for the implementation of XIAP sequencing in clinical diagnostics in male patients with severe CD. (Source: Gut)
Source: Gut - December 8, 2014 Category: Gastroenterology Authors: Zeissig, Y., Petersen, B.-S., Milutinovic, S., Bosse, E., Mayr, G., Peuker, K., Hartwig, J., Keller, A., Kohl, M., Laass, M. W., Billmann-Born, S., Brandau, H., Feller, A. C., Rocken, C., Schrappe, M., Rosenstiel, P., Reed, J. C., Schreiber, S., Franke, A Tags: Crohn's disease, Editor's choice Inflammatory bowel disease Source Type: research

Long-term adenoma recurrence following wide-field endoscopic mucosal resection (WF-EMR) for advanced colonic mucosal neoplasia is infrequent: results and risk factors in 1000 cases from the Australian Colonic EMR (ACE) study
Conclusions Following colonic WF-EMR, early recurrent/residual adenoma occurs in 16%, and is usually unifocal and diminutive. Risk factors were identified. Late recurrence occurs in 4%. Overall, recurrence was managed endoscopically in 93% of cases. Recurrence is not a significant clinical problem following WF-EMR, as with strict colonoscopic surveillance, it can be managed endoscopically with high success rates. Trial registration number: NCT01368289. (Source: Gut)
Source: Gut - December 8, 2014 Category: Gastroenterology Authors: Moss, A., Williams, S. J., Hourigan, L. F., Brown, G., Tam, W., Singh, R., Zanati, S., Burgess, N. G., Sonson, R., Byth, K., Bourke, M. J. Tags: Endoscopy, Colon cancer Source Type: research

The combination of autofluorescence endoscopy and molecular biomarkers is a novel diagnostic tool for dysplasia in Barrett's oesophagus
Objective Endoscopic surveillance for Barrett's oesophagus (BO) is limited by sampling error and the subjectivity of diagnosing dysplasia. We aimed to compare a biomarker panel on minimal biopsies directed by autofluorescence imaging (AFI) with the standard surveillance protocol to derive an objective tool for dysplasia assessment. Design We performed a cross-sectional prospective study in three tertiary referral centres. Patients with BO underwent high-resolution endoscopy followed by AFI-targeted biopsies. 157 patients completed the biopsy protocol. Aneuploidy/tetraploidy; 9p and 17p loss of heterozygosity; RUNX3, HPP1 ...
Source: Gut - December 8, 2014 Category: Gastroenterology Authors: di Pietro, M., Boerwinkel, D. F., Shariff, M. K., Liu, X., Telakis, E., Lao-Sirieix, P., Walker, E., Couch, G., Mills, L., Nuckcheddy-Grant, T., Slininger, S., O'Donovan, M., Visser, M., Meijer, S. L., Kaye, P. V., Wernisch, L., Ragunath, K., Bergman, J. Tags: Open access, Oesophageal cancer Endoscopy Source Type: research

OCT1 is a determinant of synbindin-related ERK signalling with independent prognostic significance in gastric cancer
Conclusions OCT1 is a driver of synbindin-mediated ERK signalling and a promising marker for the prognosis and molecular subtyping of GC. (Source: Gut)
Source: Gut - December 8, 2014 Category: Gastroenterology Authors: Qian, J., Kong, X., Deng, N., Tan, P., Chen, H., Wang, J., Li, Z., Hu, Y., Zou, W., Xu, J., Fang, J.-Y. Tags: Open access, Pancreatic cancer Stomach Source Type: research

TBL1XR1 promotes lymphangiogenesis and lymphatic metastasis in esophageal squamous cell carcinoma
Conclusions Our results demonstrated that TBL1XR1 induced lymphangiogenesis and lymphatic metastasis in ESCC via upregulation of VEGF-C, and may represent a novel prognostic biomarker and therapeutic target for patients with ESCC. (Source: Gut)
Source: Gut - December 8, 2014 Category: Gastroenterology Authors: Liu, L., Lin, C., Liang, W., Wu, S., Liu, A., Wu, J., Zhang, X., Ren, P., Li, M., Song, L. Tags: Oesophageal cancer Oesophagus Source Type: research

Oesophageal adenocarcinoma and prior diagnosis of Barrett's oesophagus: a population-based study
Objective Endoscopic surveillance of Barrett's oesophagus (BO) provides an opportunity to detect early stage oesophageal adenocarcinoma (OAC). We sought to determine the proportion of OAC patients with a prior diagnosis of BO on a population basis and to evaluate the influence of a prior diagnosis of BO on survival, taking into account lead and length time biases. Design A retrospective population-based study of all OAC patients in Northern Ireland between 2003 and 2008. A prior BO diagnosis was determined by linkage to the Northern Ireland BO register. Stage distribution at diagnosis and histological grade were compared ...
Source: Gut - December 8, 2014 Category: Gastroenterology Authors: Bhat, S. K., McManus, D. T., Coleman, H. G., Johnston, B. T., Cardwell, C. R., McMenamin, U., Bannon, F., Hicks, B., Kennedy, G., Gavin, A. T., Murray, L. J. Tags: Oesophageal cancer Oesophagus Source Type: research

The human squamous oesophagus has widespread capacity for clonal expansion from cells at diverse stages of differentiation
Objective Knowledge of the cellular mechanisms involved in homeostasis of human squamous oesophagus in the steady state and following chronic injury is limited. We aimed to better understand these mechanisms by using a functional 3D approach. Design Proliferation, mitosis and the expression of progenitor lineage markers were assessed in normal squamous oesophagus from 10 patients by immunofluorescence on 3D epithelial whole mounts. Cells expressing differential levels of epithelial and progenitor markers were isolated using flow cytometry sorting and characterised by qPCR and IF. Their self-renewing potential was investig...
Source: Gut - December 8, 2014 Category: Gastroenterology Authors: Barbera, M., di Pietro, M., Walker, E., Brierley, C., MacRae, S., Simons, B. D., Jones, P. H., Stingl, J., Fitzgerald, R. C. Tags: Open access Oesophagus Source Type: research

Targeting of gut specific leucocyte recruitment in IBD by vedolizumab
IBD is characterised by an inappropriate immune response to our own gut microbiota in the setting of a genetically susceptible individual. The consequence of this dysregulated process is activation of the innate immune system which in turn produces cytokines such as tumour necrosis factor α (TNFα) and activation of the adaptive immune system with subsequent recruitment of pro-inflammatory T and B cells to the colon or small bowel. This in turn leads to further amplification of pro-inflammatory cytokines release which bind to cognate receptors and activation of intercellular pathway such as JAK and STAT to media...
Source: Gut - December 8, 2014 Category: Gastroenterology Authors: Eksteen, B. Tags: Commentary Source Type: research

Treatment of paediatric cholestasis due to canalicular transport defects: yet another step forward
Paediatric cholestasis is a rare but devastating group of diseases that usually manifest in infancy or childhood by impaired bile secretion, due to either primary or secondary alterations affecting the liver secretory machinery, and that may progress to cirrhosis and liver failure. Although there is resemblance in clinical symptoms, the cause of these diseases can be completely different, which is important because it determines, among others, the response to treatment. For a specific subgroup of cholestatic diseases, namely those associated with canalicular transport defects, our pathophysiological understanding has been ...
Source: Gut - December 8, 2014 Category: Gastroenterology Authors: Marin, J. J. G., Houwen, R. H. J. Tags: Commentary Source Type: research

Does a prior diagnosis of Barrett's oesophagus influence risk of dying from oesophageal adenocarcinoma?
In many industrialised populations, adenocarcinoma of the oesophagus holds the dubious distinction of being the cancer for which the proportional rise in incidence has been most rapid.1 The factors conferring increased risks are well established, including obesity, gastro-oesophageal acid reflux, smoking and male sex.2 It has also long been known that Barrett's oesophagus, the metaplastic precursor, has a measurable rate of progressing to cancer. This observation has given rise to the notion that screening or surveillance for Barrett's oesophagus should, in theory, reduce the risks of dying from oesophageal adenocarcinoma....
Source: Gut - December 8, 2014 Category: Gastroenterology Authors: Whiteman, D. C. Tags: Commentary Source Type: research

Novel strategies for liver therapy using stem cells
The clinical need Liver disease is an increasing clinical burden, causing over 10 000 deaths last year in the UK alone (http://www.britishlivertrust.org.uk). Liver insufficiency describes the clinical situation in which cumulative (chronic) or one-off massive (acute) insults exceed the liver's normal physiological capacity to functionally regenerate. Untreated, liver insufficiency invariably leads to death. The current gold standard of care in this setting is whole organ transplantation. Due to the increasing burden of disease within the population, however, the number of patients requiring transplantation far exceeds...
Source: Gut - December 8, 2014 Category: Gastroenterology Authors: Rashid, T., Takebe, T., Nakauchi, H. Tags: Leading article Source Type: research

GI highlights from the literature
In this study, the authors set out to investigate the origin of the intestinal TRM compartment in mice from birth until adulthood. Using a combination of immunotyping, lineage tracing and parabiosis techniques, the authors demonstrated that macrophages in the intestine are an exception to this paradigm. Specifically, intestinal macrophages under steady-state conditions are continuously replenished by blood-derived monocytes even though the yolk sac-derived macrophages are seeded to the gut tissue... (Source: Gut)
Source: Gut - October 31, 2014 Category: Gastroenterology Authors: McLean, M. H. Tags: JournalScan Source Type: research

A 75-year-old woman with multifocal jejunal strictures
Clinical presentation A previously fit and well 75-year-old Caucasian woman presented with a 2-month history of postprandial abdominal pain, vomiting and 10 kg weight loss without diarrhoea. Blood investigations showed marked hypoalbuminaemia of 18 g/L and elevated C reactive protein (CRP) of 185 mg/L. Tissue transglutaminase IgA level was within normal limits without evidence of IgA deficiency. Faecal calprotectin was elevated at 205 µg/g. Abdominal CT revealed subacute small bowel obstruction characterised by multiple long, thick walled, dilated loops of jejunum (figure 1) associated with lympha...
Source: Gut - October 31, 2014 Category: Gastroenterology Authors: Lee, H. Y., Howarth, G., Willert, R. Tags: GUT Snapshot Editor ' s quiz: GI snapshot Source Type: research

Correction
Canto MI, Harinck F, Hruban RH, et al. International Cancer of the Pancreas Screening (CAPS) Consortium summit on the management of patients with increased risk for familial pancreatic cancer. Gut 2013;62:339–47. The Collaborator Pascal Hammell's name should read Pascal Hammel. (Source: Gut)
Source: Gut - October 31, 2014 Category: Gastroenterology Tags: Correction Source Type: research

Gastroparesis: separate entity or just a part of dyspepsia?
Gastroparesis is defined by the presence of delayed gastric emptying (GE) in the absence of mechanical obstruction. Symptoms that have been attributed to gastroparesis include postprandial fullness, early satiation nausea and vomiting. Gastroprokinetic drugs are the preferred treatment option. A number of problems with the concept of gastroparesis have been identified recently. Major overlap exists with the symptom complex of the functional dyspepsia subtype of postprandial distress syndrome. The distinguishing feature of gastroparesis is delayed GE, but the correlation between delayed emptying and symptom pattern or sever...
Source: Gut - October 31, 2014 Category: Gastroenterology Authors: Stanghellini, V., Tack, J. Tags: GUT Recent advances in clinical practice, Dyspepsia, Gastric emptying disorders, Stomach and duodenum Source Type: research

CCL2-dependent infiltrating macrophages promote angiogenesis in progressive liver fibrosis
Conclusions Inflammation-associated angiogenesis is promoted by CCL2-dependent monocytes during fibrosis progression. Innovative in vivo µCT methodology can accurately monitor angiogenesis and antiangiogenic therapy effects in experimental liver fibrosis. (Source: Gut)
Source: Gut - October 31, 2014 Category: Gastroenterology Authors: Ehling, J., Bartneck, M., Wei, X., Gremse, F., Fech, V., Mockel, D., Baeck, C., Hittatiya, K., Eulberg, D., Luedde, T., Kiessling, F., Trautwein, C., Lammers, T., Tacke, F. Tags: Cirrhosis, Pancreas and biliary tract, Hepatic cancer Hepatology Source Type: research

Hypoxia induced downregulation of hepcidin is mediated by platelet derived growth factor BB
Conclusions Hypoxia decreases hepatic hepcidin expression by a novel regulatory pathway exerted via PDGF-BB, leading to increased availability of circulating iron that can be used for erythropoiesis. (Source: Gut)
Source: Gut - October 31, 2014 Category: Gastroenterology Authors: Sonnweber, T., Nachbaur, D., Schroll, A., Nairz, M., Seifert, M., Demetz, E., Haschka, D., Mitterstiller, A.-M., Kleinsasser, A., Burtscher, M., Trubsbach, S., Murphy, A. T., Wroblewski, V., Witcher, D. R., Mleczko-Sanecka, K., Vecchi, C., Muckenthaler, M Tags: Hepatology Source Type: research

Patients with chronic hepatitis B treated with oral antiviral therapy retain a higher risk for HCC compared with patients with inactive stage disease
Background It is generally stated that oral antiviral therapy in patients with chronic hepatitis B (CHB) decreases the risk of developing hepatocellular carcinoma (HCC). Although oral nucleos(t)ide analogues (NUCs) may induce a state similar to inactive stage CHB, the long-term risk for HCC in patients treated with NUCs compared with inactive CHB is unclear. Methods A total of 1378 patients who were treatment naïve and started NUC therapy and 1014 patients with inactive stage CHB who were HBeAg-negative and continuously had hepatitis B DNA
Source: Gut - October 31, 2014 Category: Gastroenterology Authors: Cho, J.-Y., Paik, Y.-H., Sohn, W., Cho, H. C., Gwak, G.-Y., Choi, M. S., Lee, J. H., Koh, K. C., Paik, S. W., Yoo, B. C. Tags: Cirrhosis, Hepatitis B, Hepatic cancer Hepatology Source Type: research

Bacterial genotoxin colibactin promotes colon tumour growth by inducing a senescence-associated secretory phenotype
Conclusion These data reveal a new paradigm for carcinogenesis, in which colibactin-induced senescence has an important role. (Source: Gut)
Source: Gut - October 31, 2014 Category: Gastroenterology Authors: Cougnoux, A., Dalmasso, G., Martinez, R., Buc, E., Delmas, J., Gibold, L., Sauvanet, P., Darcha, C., Dechelotte, P., Bonnet, M., Pezet, D., Wodrich, H., Darfeuille-Michaud, A., Bonnet, R. Tags: Colon cancer Source Type: research

Type I interferon signalling in the intestinal epithelium affects Paneth cells, microbial ecology and epithelial regeneration
Conclusions IFNAR1 in IECs, and Paneth cells in particular, contributes to the regulation of the host–microbiota relationship, with consequences for intestinal regeneration and colitis-associated tumour formation. (Source: Gut)
Source: Gut - October 31, 2014 Category: Gastroenterology Authors: Tschurtschenthaler, M., Wang, J., Fricke, C., Fritz, T. M. J., Niederreiter, L., Adolph, T. E., Sarcevic, E., Kunzel, S., Offner, F. A., Kalinke, U., Baines, J. F., Tilg, H., Kaser, A. Tags: Crohn's disease Gut microbiota Source Type: research

Exercise and associated dietary extremes impact on gut microbial diversity
Conclusions The results provide evidence for a beneficial impact of exercise on gut microbiota diversity but also indicate that the relationship is complex and is related to accompanying dietary extremes. (Source: Gut)
Source: Gut - October 31, 2014 Category: Gastroenterology Authors: Clarke, S. F., Murphy, E. F., O'Sullivan, O., Lucey, A. J., Humphreys, M., Hogan, A., Hayes, P., O'Reilly, M., Jeffery, I. B., Wood-Martin, R., Kerins, D. M., Quigley, E., Ross, R. P., O'Toole, P. W., Molloy, M. G., Falvey, E., Shanahan, F., Cotter, P. D. Tags: Editor's choice, Press releases Gut microbiota Source Type: research

Involvement of interleukin-17A-induced expression of heat shock protein 47 in intestinal fibrosis in Crohn's disease
Conclusions IL-17A-induced HSP47 expression is involved in collagen I expression in ISEMFs, which might contribute to intestinal fibrosis in CD. (Source: Gut)
Source: Gut - October 31, 2014 Category: Gastroenterology Authors: Honzawa, Y., Nakase, H., Shiokawa, M., Yoshino, T., Imaeda, H., Matsuura, M., Kodama, Y., Ikeuchi, H., Andoh, A., Sakai, Y., Nagata, K., Chiba, T. Tags: Crohn's disease Inflammatory bowel disease Source Type: research

{alpha}-Haemolysin of Escherichia coli in IBD: a potentiator of inflammatory activity in the colon
Conclusions E coli HlyA impairs intestinal barrier function via focal leak induction in the epithelium, thereby intensifying antigen uptake and triggering intestinal inflammation in vulnerable mouse models. Therefore, HlyA-expressing E coli strains should be considered as potential cofactors in the pathogenesis of intestinal inflammation. (Source: Gut)
Source: Gut - October 31, 2014 Category: Gastroenterology Authors: Bucker, R., Schulz, E., Gunzel, D., Bojarski, C., Lee, I.-F. M., John, L. J., Wiegand, S., Janssen, T., Wieler, L. H., Dobrindt, U., Beutin, L., Ewers, C., Fromm, M., Siegmund, B., Troeger, H., Schulzke, J.-D. Tags: Crohn's disease, Ulcerative colitis Inflammatory bowel disease Source Type: research

Prolactin mediates psychological stress-induced dysfunction of regulatory T cells to facilitate intestinal inflammation
Conclusions Psychological stress-derived prolactin alters DC and Treg's properties to contribute to intestinal inflammation. (Source: Gut)
Source: Gut - October 31, 2014 Category: Gastroenterology Authors: Wu, W., Sun, M., Zhang, H.-P., Chen, T., Wu, R., Liu, C., Yang, G., Geng, X.-R., Feng, B.-S., Liu, Z., Liu, Z., Yang, P.-C. Tags: Open access Mucosal immunity Source Type: research

Histamine H4 and H1 receptors contribute to postinflammatory visceral hypersensitivity
Conclusions H4R and H1R antagonists dose-dependently reduce and even normalise postinflammatory visceral hypersensitivity via different underlying mechanisms but with a synergistic effect. Both receptor subtypes represent promising targets for the treatment of postinflammatory visceral hypersensitivity. (Source: Gut)
Source: Gut - October 31, 2014 Category: Gastroenterology Authors: Deiteren, A., De Man, J. G., Ruyssers, N. E., Moreels, T. G., Pelckmans, P. A., De Winter, B. Y. Tags: Endoscopy, Gastrointestinal hormones, Colon cancer Neurogastroenterology Source Type: research

Double oral esomeprazole after a 3-day intravenous esomeprazole infusion reduces recurrent peptic ulcer bleeding in high-risk patients: a randomised controlled study
Background Patients with high Rockall scores have increased risk of ulcer rebleeding after 3-day esomeprazole infusions. Objective To investigate whether double oral esomeprazole given after a 3-day esomeprazole infusion decreases ulcer rebleeding for patients with high Rockall scores. Design We prospectively enrolled 293 patients with peptic ulcer bleeding who had achieved endoscopic haemostasis. After a 3-day esomeprazole infusion, patients with Rockall scores ≥6 were randomised into the oral double-dose group (n=93) or the oral standard-dose group (n=94) to receive 11 days of oral esomeprazole 40 mg twice...
Source: Gut - October 31, 2014 Category: Gastroenterology Authors: Cheng, H.-C., Wu, C.-T., Chang, W.-L., Cheng, W.-C., Chen, W.-Y., Sheu, B.-S. Tags: Ulcer Stomach Source Type: research

The stem cell organisation, and the proliferative and gene expression profile of Barrett's epithelium, replicates pyloric-type gastric glands
Conclusions Barrett's shows the proliferative and stem cell architecture, and pattern of gene expression of pyloric gastric glands, maintained by stem cells showing gastric and intestinal differentiation: neutral drift may suggest that intestinal differentiation advances with time, a concept critical for the understanding of the origin and development of Barrett's oesophagus. (Source: Gut)
Source: Gut - October 31, 2014 Category: Gastroenterology Authors: Lavery, D. L., Nicholson, A. M., Poulsom, R., Jeffery, R., Hussain, A., Gay, L. J., Jankowski, J. A., Zeki, S. S., Barr, H., Harrison, R., Going, J., Kadirkamanathan, S., Davis, P., Underwood, T., Novelli, M. R., Rodriguez-Justo, M., Shepherd, N., Jansen, Tags: Open access, Oesophageal cancer Oesophagus Source Type: research

Systematic review: monotherapy with antitumour necrosis factor {alpha} agents versus combination therapy with an immunosuppressive for IBD
Introduction The treatment of IBD has evolved significantly over the past 15 years. Historically, steroids and immunosuppressive drugs, such as methotrexate (MTX), azathioprine (AZA) and 6-mercaptopurine (6-MP) had been the mainstay of therapy. When infliximab (IFX) was approved for the treatment of Crohn's disease, it began the era of trying to understand how best to optimise our available treatment options. Initially, antitumour necrosis factor (anti-TNF) agents were used after immunosuppressives failed. Then, evidence showed that using AZA together with IFX early in the disease course was more effective than the ty...
Source: Gut - October 31, 2014 Category: Gastroenterology Authors: Dulai, P. S., Siegel, C. A., Colombel, J.-F., Sandborn, W. J., Peyrin-Biroulet, L. Tags: Crohn's disease Leading article Source Type: research

Linking hypoxia and iron homeostasis: a 'plate' full of factors
Hepcidin, a 25-amino acid peptide expressed almost exclusively in the liver, is the central regulator of systemic body iron homeostasis. Since its initial identification and characterisation as an antimicrobial peptide, it has become clear that hepcidin plays a role in many metabolic processes. Mutations in hepcidin lead to one form of the severe iron overload disorder juvenile haemochromatosis (type 2B). Hepcidin is a negative regulator of iron absorption and recycling; under normal conditions, increased iron in the body results in an enhanced secretion of hepcidin by the liver, the central organ responsible for iron regu...
Source: Gut - October 31, 2014 Category: Gastroenterology Authors: Subramaniam, V. N., Wallace, D. F. Tags: Commentary Source Type: research

The gut microbiota, dietary extremes and exercise
The GI tract is colonised by trillions of bacteria in a complex community collectively referred to as the gut microbiota. This metabolically active ‘foreign’ body contributes to host metabolism and immune system development and changes in its composition have been implicated in many chronic diseases including obesity and diabetes. Under normal conditions, this metabolically active ‘foreign’ body exists in a state of symbiotic tolerance (eubiosis) with its host and remains relatively stable over time. One of the major influences on the gut microbiota, at least in terms of our ability to modulate it, ...
Source: Gut - October 31, 2014 Category: Gastroenterology Authors: Hold, G. L. Tags: Press releases Commentary Source Type: research

Pathobiont hypnotises enterocytes to promote tumour development
INTRODUCTION Cougnoux and colleagues1 report a new mechanism by which select bacteria can drive colon cancer. Specifically, they discovered that colobactin-producing E. coli strains can activate growth-arrested (ie, senescent) cells to produce growth factors that drive tumor growth. These findings may, in part, underlie the association of such bacteria with carcinomas and could result in novel strategies to slow tumor growth. Approximately 20% of cancers are considered to be a consequence of infection by bacteria and/or viruses typically classified as pathogens. Moreover, many cancers occur in tissues with high exposure to...
Source: Gut - October 31, 2014 Category: Gastroenterology Authors: Chassaing, B., Gewirtz, A. T. Tags: Commentary Source Type: research

Histamine antagonism and postinflammatory visceral hypersensitivity
Abdominal pain is one of the most difficult to treat symptoms in patients suffering from IBS. Recent evidence shows that abnormal perception of visceral stimuli, or visceral hypersensitivity, represents an important underlying mechanism. Of interest, similar mechanisms may be involved in abdominal pain reported by UC and Crohn's disease patients in remission. Although the underlying mechanisms are not fully understood, it becomes increasingly clear that intestinal inflammation may provide an initial stimulus for a persistent state of visceral hypersensitivity. Most insight in the role of inflammation in chronic abdominal p...
Source: Gut - October 31, 2014 Category: Gastroenterology Authors: Wouters, M. M. Tags: Commentary Source Type: research

CCL2: a link between hepatic inflammation, fibrosis and angiogenesis?
Liver fibrosis develops as a result of an excessive accumulation of extracellular matrix mostly in the context of chronic liver injury. The progression of liver fibrosis may lead to the development of cirrhosis and eventually hepatocellular carcinoma. Only in recent years has angiogenesis been considered as a concomitant process along the progression of liver fibrosis.1 Moreover, angiogenesis has been shown to be of key importance during the development, growth and progression of hepatocellular carcinoma, one of the most vascularised tumours. However, whether angiogenesis determines the progression of liver fibrosis or is ...
Source: Gut - October 31, 2014 Category: Gastroenterology Authors: Affo, S., Sancho-Bru, P. Tags: Commentary Source Type: research

Does suppression of HBV replication by antiviral therapy confer the same benefit as host immune control of HBV?
This study... (Source: Gut)
Source: Gut - October 31, 2014 Category: Gastroenterology Authors: Yapali, S., Lok, A. S. Tags: Commentary Source Type: research

Study of Mendelian forms of Crohn's disease in Saudi Arabia reveals novel risk loci and alleles
Sir, We read with interest the article by Uhlig on the Mendelian forms of IBD.1 Mendelian forms of Crohn's disease (CD) are rare but can establish a causal link that is not usually possible by the genome-wide association study (GWAS) design. In order to accelerate the discovery of Mendelian CD, we recruited four cooperative families in which the healthy consanguineous parents had at least two affected children with early onset CD (
Source: Gut - October 2, 2014 Category: Gastroenterology Authors: Patel, N., El Mouzan, M. I., Al-Mayouf, S. M., Adly, N., Mohamed, J. Y., Al Mofarreh, M. A., Ibrahim, N., Xiong, Y., Zhao, Q., Al-Saleem, K. A., Alkuraya, F. S. Tags: PostScript Source Type: research

Dependence receptors and colorectal cancer
The research on colorectal cancer (CRC) biology has been leading the oncology field since the early 1990s. The search for genetic alterations has allowed the identification of the main tumour suppressors or oncogenes. Recent work obtained in CRC has unexpectedly proposed the existence of novel category of tumour suppressors, the so-called ‘dependence receptors’. These transmembrane receptors behave as Dr Jekyll and Mr Hyde with two opposite sides: they induce a positive signalling (survival, proliferation, differentiation) in presence of their ligand, but are not inactive in the absence of their ligand and rath...
Source: Gut - October 2, 2014 Category: Gastroenterology Authors: Mehlen, P., Tauszig-Delamasure, S. Tags: GUT Recent advances in basic science, Colon cancer Source Type: research

GI highlights from the literature
Basic scienceA novel method of liver preservation may alleviate the shortage of donor organs  Berendsen TA, Bruinsma BG, Puts CF, et al. Supercooling enables long-term transplantation survival following 4 days of liver preservation. Nat Med 2014;20:790–3. There is a shortage of donor organs for transplantation worldwide. One strategy to increase availability is to enhance organ preservation and allow more potentially available organs to be used successfully. Currently, viable preservation is available up to 12 h. Although various methods of supercooling to enhance preservation have been assessed, there...
Source: Gut - October 2, 2014 Category: Gastroenterology Authors: McLean, M. H. Tags: JournalScan Source Type: research

Osteopontin induces ductular reaction contributing to liver fibrosis
Conclusions OPN emerges as a key matricellular protein driving DR and contributing to scarring and liver fibrosis via TGF-β. (Source: Gut)
Source: Gut - October 2, 2014 Category: Gastroenterology Authors: Wang, X., Lopategi, A., Ge, X., Lu, Y., Kitamura, N., Urtasun, R., Leung, T.-M., Fiel, M. I., Nieto, N. Tags: Cirrhosis, Pancreas and biliary tract Hepatology Source Type: research

Cell cycle-related kinase mediates viral-host signalling to promote hepatitis B virus-associated hepatocarcinogenesis
Background Androgen receptor (AR) signalling contributes to male predominance in hepatocellular carcinoma (HCC), which is more pronounced in HBV-endemic areas. Cell cycle-related kinase (CCRK) is essential for AR-induced hepatocarcinogenesis but its molecular function in HBV-associated HCC remains obscure. Objective To determine the molecular function of CCRK in HBV-associated HCC. Design Transcriptional regulation was assessed by chromatin immunoprecipitation, promoter mutation and luciferase reporter assays. Hepatocellular proliferation and tumourigenesis were examined by colony formation, soft agar assays and using HB...
Source: Gut - October 2, 2014 Category: Gastroenterology Authors: Yu, Z., Gao, Y.-Q., Feng, H., Lee, Y.-Y., Li, M. S., Tian, Y., Go, M. Y. Y., Yu, D.-Y., Cheung, Y.-S., Lai, P. B. S., Yu, J., Wong, V. W. S., Sung, J. J. Y., Chan, H. L. Y., Cheng, A. S. L. Tags: Hepatic cancer Hepatology Source Type: research

CCL20 mediates lipopolysaccharide induced liver injury and is a potential driver of inflammation and fibrosis in alcoholic hepatitis
Conclusions Our results suggest that CCL20 upregulation is strongly associated with LPS and may not only represent a new potential biomarker to predict outcome in patients with AH but also an important mediator linking hepatic inflammation, injury and fibrosis in AH. (Source: Gut)
Source: Gut - October 2, 2014 Category: Gastroenterology Authors: Affo, S., Morales-Ibanez, O., Rodrigo-Torres, D., Altamirano, J., Blaya, D., Dapito, D. H., Millan, C., Coll, M., Caviglia, J. M., Arroyo, V., Caballeria, J., Schwabe, R. F., Gines, P., Bataller, R., Sancho-Bru, P. Tags: Hepatitis other Hepatology Source Type: research