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   ISSN (Print) 0017-5749 - ISSN (Online) 1468-3288
   Published by BMJ Publishing Group Homepage  [57 journals]
  • Cholangiocytes and the environment in primary sclerosing cholangitis:
           where is the link'
    • Authors: OHara, S. P; Karlsen, T. H, LaRusso, N. F.
      Pages: 1873 - 1877
      Abstract: In primary sclerosing cholangitis (PSC), annular fibrosis around intrahepatic and extrahepatic bile ducts leads to progressive liver disease for which there is no effective therapy except liver transplantation.1 The concentric accumulation of connective tissue around bile ducts suggests that the cholangiocyte plays an integral role in PSC pathogenesis. However, what initiates changes in cholangiocyte phenotype and how cholangiocytes interact with cells in the peribiliary extracellular matrix like immune cells and stromal components is largely unknown. Over the last 10 years, genome-wide association studies in PSC have revealed>20 risk genes.2–5 A significant observation that can be derived from these data, which also applies to other non-Mendelian phenotypes, is that the predominant risk contribution is likely to come from one or more environmental sources, rather than the genetic aberrations. Indeed, in PSC, we estimate that
      Keywords: Open access, Gut
      PubDate: 2017-10-09T05:31:50-07:00
      DOI: 10.1136/gutjnl-2017-314249
      Issue No: Vol. 66, No. 11 (2017)
  • Neutrophils diminish T-cell immunity to foster gastric cancer progression:
           the role of GM-CSF/PD-L1/PD-1 signalling pathway
    • Authors: Zhang, X; Xu, W.
      Pages: 1878 - 1880
      Abstract: Neutrophils are the predominant leucocytes in the blood and act as the first line of host defence against invading pathogens. Neutrophils have also been shown to play important roles in the other pathological conditions, including cancer. In the past decade, many efforts have been made to clarify the roles of neutrophils in cancer development and progression. It appears that neutrophils have both antitumour and protumour functions.1 On one hand, neutrophils can directly kill tumour cells by releasing antimicrobial and cytotoxic contents that are prestored in their granules. Neutrophils can induce apoptosis in tumour cells and reduce tumour growth when administrated into tumour-bearing animals. Neutrophils are regarded as important effector cells for monoclonal antibody (mAb)-mediated immunotherapy, where they interact with mAb through the Fc receptor, leading to antibody-dependent cell cytotoxicity. Neutrophils also have antimetastatic activity. In mouse models of cancer metastasis, neutrophils at the premetastatic site produce cytotoxic...
      Keywords: Open access
      PubDate: 2017-10-09T05:31:50-07:00
      DOI: 10.1136/gutjnl-2017-313923
      Issue No: Vol. 66, No. 11 (2017)
  • Improving iron supplements: cooking with GOS
    • Authors: Drakesmith, H; Allen, S. J.
      Pages: 1881 - 1882
      Abstract: Iron is essential for oxygen transport, generation of energy, synthesis of DNA and multiple enzymatic systems. Iron deficiency impairs these functions and a familiar and important manifestation of advanced iron deficiency is anaemia. Around a quarter of a billion children worldwide are anaemic, and at least half of childhood anaemia is caused in part by a lack of iron; a heavy burden of anaemia is especially present in sub-Saharan Africa and South Asia.1 Iron replenishments, including iron-containing multiple micronutrient powders (MNPs) can be effective treatments to increase haemoglobin. However, despite the use of such agents for many years, the estimated prevalence of anaemia worldwide in preschool children only decreased from 47% to 43% between 1993 and 2011.2 Furthermore, iron replenishments have been associated with adverse events, including infections, intestinal inflammation and diarrhoea in some (but not all) trials. There is a need to make iron...
      Keywords: Gut
      PubDate: 2017-10-09T05:31:50-07:00
      DOI: 10.1136/gutjnl-2017-314593
      Issue No: Vol. 66, No. 11 (2017)
  • Inulin prebiotic: is it all about bifidobacteria'
    • Authors: Claus; S. P.
      Pages: 1883 - 1884
      Abstract: In this issue, Vandeputte et al1 present a unique study exploring the effects of chicory-derived inulin on the human gut microbiota by combining Next Generation Sequencing and faecal metabolomics to gain new insights into the mechanisms of action underlying inulin's health-promoting effects. The study supports that inulin prebiotics stimulate growth of bifidobacteria while simultaneously driving a number of other modulations of the gut microbial ecosystem that may be associated with health-promoting effects. Consumption of inulin-type fructans (ITFs) has been associated with a number of health benefits, including normalisation of GI function, regulation of body weight gain and energy metabolism.2 Some of the suggested mechanisms of action include regulation of the immune system, modulation of GI peptides, production of short chain fatty acids (SCFAs) and modulation of triglyceride metabolism.2–4 Down in the intestine, ITFs have long been known for their...
      PubDate: 2017-10-09T05:31:50-07:00
      DOI: 10.1136/gutjnl-2017-313800
      Issue No: Vol. 66, No. 11 (2017)
  • Race-specific differences in mucosal sulfidogenic bacteria modify colon
           cancer risk
    • Authors: Kinross; J.
      Pages: 1884 - 1885
      Abstract: Over the past 10 years, the incidence and mortality of colorectal cancer (CRC) in the USA has steadily declined. However, this fall has been less dramatic among African-Americans (AA), who continue to have the highest rates of mortality from CRC when compared with other ethnic subgroups.1 The reasons for the health disparities are multifactorial and represent socioeconomic factors and barriers to effective screening. The gut microbiome is increasingly implicated as a critical cometabolic engine that mediates the impact of environmental modifiers such as diet in high-risk cohorts.2 Despite the emergence of several theories for the role of the gut microbiome in colon cancer initiation, a precise mechanism has yet to be definitively elucidated.3 4 A major challenge is deciphering the huge range of molecular signalling languages the microbiome uses to influence human health. The intestinal microbiota plays a central role in digestive...
      PubDate: 2017-10-09T05:31:50-07:00
      DOI: 10.1136/gutjnl-2017-313989
      Issue No: Vol. 66, No. 11 (2017)
  • Quality standards in upper gastrointestinal endoscopy: a position
           statement of the British Society of Gastroenterology (BSG) and Association
           of Upper Gastrointestinal Surgeons of Great Britain and Ireland (AUGIS)
    • Authors: Beg, S; Ragunath, K, Wyman, A, Banks, M, Trudgill, N, Pritchard, M. D, Riley, S, Anderson, J, Griffiths, H, Bhandari, P, Kaye, P, Veitch, A.
      Pages: 1886 - 1899
      Abstract: This document represents the first position statement produced by the British Society of Gastroenterology and Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland, setting out the minimum expected standards in diagnostic upper gastrointestinal endoscopy. The need for this statement has arisen from the recognition that while technical competence can be rapidly acquired, in practice the performance of a high-quality examination is variable, with an unacceptably high rate of failure to diagnose cancer at endoscopy. The importance of detecting early neoplasia has taken on greater significance in this era of minimally invasive, organ-preserving endoscopic therapy. In this position statement we describe 38 recommendations to improve diagnostic endoscopy quality. Our goal is to emphasise practices that encourage mucosal inspection and lesion recognition, with the aim of optimising the early diagnosis of upper gastrointestinal disease and improving patient outcomes.
      Keywords: Open access, Gut
      PubDate: 2017-10-09T05:31:50-07:00
      DOI: 10.1136/gutjnl-2017-314109
      Issue No: Vol. 66, No. 11 (2017)
  • Tumour-activated neutrophils in gastric cancer foster immune suppression
           and disease progression through GM-CSF-PD-L1 pathway
    • Authors: Wang, T.-t; Zhao, Y.-l, Peng, L.-s, Chen, N, Chen, W, Lv, Y.-p, Mao, F.-y, Zhang, J.-y, Cheng, P, Teng, Y.-s, Fu, X.-l, Yu, P.-w, Guo, G, Luo, P, Zhuang, Y, Zou, Q.-m.
      Pages: 1900 - 1911
      Abstract: ObjectiveNeutrophils are prominent components of solid tumours and exhibit distinct phenotypes in different tumour microenvironments. However, the nature, regulation, function and clinical relevance of neutrophils in human gastric cancer (GC) are presently unknown.DesignFlow cytometry analyses were performed to examine levels and phenotype of neutrophils in samples from 105 patients with GC. Kaplan-Meier plots for overall survival were performed using the log-rank test. Neutrophils and T cells were isolated, stimulated and/or cultured for in vitro and in vivo regulation and function assays.ResultsPatients with GC showed a significantly higher neutrophil infiltration in tumours. These tumour-infiltrating neutrophils showed an activated CD54+ phenotype and expressed high level immunosuppressive molecule programmed death-ligand 1 (PD-L1). Neutrophils activated by tumours prolonged their lifespan and strongly expressed PD-L1 proteins with similar phenotype to their status in GC, and significant correlations were found between the levels of PD-L1 and CD54 on tumour-infiltrating neutrophils. Moreover, these PD-L1+ neutrophils in tumours were associated with disease progression and reduced GC patient survival. Tumour-derived GM-CSF activated neutrophils and induced neutrophil PD-L1 expression via Janus kinase (JAK)-signal transducer and activator of transcription 3 (STAT3) signalling pathway. The activated PD-L1+ neutrophils effectively suppressed normal T-cell immunity in vitro and contributed to the growth and progression of human GC in vivo; the effect could be reversed by blocking PD-L1 on these neutrophils.ConclusionsOur results illuminate a novel mechanism of PD-L1 expression on tumour-activated neutrophils in GC, and also provide functional evidence for these novel GM-CSF-PD-L1 pathways to prevent, and to treat this immune tolerance feature of GC.
      Keywords: Open access
      PubDate: 2017-10-09T05:31:50-07:00
      DOI: 10.1136/gutjnl-2016-313075
      Issue No: Vol. 66, No. 11 (2017)
  • Rare cause of abdominal pain and fever in a pregnant woman
    • Authors: Hillaire, S; Kahn, J.-E, Picone, O, Cazals-Hatem, D.
      Pages: 1911 - 1982
      Abstract: Clinical presentationA pregnant woman (third trimester) presented with intense abdominal pain, nausea and myalgia. The patient was obese (body mass index 38) and was being treated for high blood pressure, hyperuricemia and hypothyroidism. She had chronic renal deficiency related to focal segmental glomerular sclerosis requiring dialysis. The physical examination at admission revealed a fever of 39°C and an acute abdomen with abdominal guarding in the right upper quadrant without hepatomegaly or splenomegaly. There were no clinical signs of pre-eclampsia. Fetal ultrasound and a Doppler of the umbilical vessels were normal. Laboratory tests showed normal liver and liver function (total protein 95%, alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin normal). The white cell count was 10x109/l (90% neutrophils), with a normal platelet count. Blood, urine and vaginal cultures were negative. Abdominal ultrasound revealed isolated thickening of the gallbladder wall without cholelithiasis. Empirical antibiotic treatment was begun with intravenous amoxicillin. Six days later, the patient's condition had worsened with increased abdominal pain, persistent fever and liver test abnormalities (AST–ALT 6N). However, bilirubin, hepatic synthesis tests, as well as leucocyte and platelet counts were still normal. A caesarean section followed by coelioscopy was decided. Coelioscopy revealed a liver with numerous necrotic spots (see figure 1).Figure 1Diagnostic laparoscopy revealed a liver surface covered with numerous white necrotic spots.QuestionWhat is the diagnosis'
      Keywords: GUT Snapshot
      PubDate: 2017-10-09T05:31:50-07:00
      DOI: 10.1136/gutjnl-2016-313097
      Issue No: Vol. 66, No. 11 (2017)
  • Ulcerative proctitis is a frequent location of paediatric-onset UC and not
           a minor disease: a population-based study
    • Authors: Hochart, A; Gower-Rousseau, C, Sarter, H, Fumery, M, Ley, D, Spyckerelle, C, Peyrin-Biroulet, L, Laberenne, J.-E, Vasseur, F, Savoye, G, Turck, D, on Behalf of Epimad Group, Andre, Antonietti, Aouakli, Armand, Aroichane, Assi, Aubet, Auxenfants, Ayafi-Ramelot, Azzouzi, Bankovski, Barbry, Bardoux, Baron, Baudet, Bazin, Bebahani, Becqwort, Benet, Benali, Benguigui, Ben Soussan, Bental, Berkelmans, Bernet, Bernou, Bernou-Dron, Bertot, Bertiaux-Vandaële, Bertrand, Billoud, Biron, Bismuth, Bleuet, Blondel, Blondin, Bohon, Boniface, Bonniere, Bonvarlet, Bonvarlet, Boruchowicz, Bostvironnois, Boualit, Bouche, Boudaillez, Bourgeaux, Bourgeois, Bourguet, Bourienne, Branche, Bray, Brazier, Breban, Bridenne, Brihier, Brung-Lefebvre, Bulois, Burgiere, Butel, Canva, Canva-Delcambre, Capron, Cardot, Carpentier, Cartier, Cassar, Cassagnou, Castex, Catala, Cattan, Catteau, Caujolle, Cayron, Chandelier, Chantre, Charles, Charneau, Chavance-Thelu, Chirita, Choteau, Claerbout, Clergue, Coevoet, Cohen, Collet, Colombel, Coopman, Corvisart, Cortot, Couttenier, Crinquette, Crombe, Dadamessi, Dapvril, Davion, Dautreme, Debas, Degrave, Dehont, Delatre, Delcenserie, Delette, Delgrange, Delhoustal, Delmotte, Demmane, Deregnaucourt, Descombes, Desechalliers, Desmet, Desreumaux, Desseaux, Desurmont, Devienne, Devouge, Devred, Devroux, Dewailly, Dharancy, Di Fiore, Djeddi, Djedir, Dreher-Duwat, Dubois, Dubuque, Ducatillon, Duclay, Ducrocq, Ducrot, Ducrotte, Dufilho, Duhamel, Dujardin, Dumant-Forest, Dupas, Dupont, Duranton, Duriez, El Achkar, El Farisi, Elie, Elie-Legrand, Elkhaki, Eoche, Evrard, Evrard, Fatome, Filoche, Finet, Flahaut, Flamme, Foissey, Fournier, Foutrein-Comes, Foutrein, Fremond, Frere, Gallet, Gamblin, Ganga, Gerard, Geslin, Gheyssens, Ghossini, Ghrib, Gilbert, Gillet, Godard, Godard, Godchaux, Godchaux, Goegebeur, Goria, Gottrand, Gower, Grandmaison, Groux, Guedon, Guillard, Guillem, Guillemot, Guimberd, Haddouche, Hakim, Hanon, Hautefeuille, Heckestweiller, Hecquet, Hedde, Hellal, Henneresse, Heyman, Heraud, Herve, Hochain, Houssin-Bailly, Houcke, Huguenin, Iobagiu, Ivanovic, Iwanicki-Caron, Janicki, Jarry, Jeu, Joly, Jonas, Katherin, Kerleveo, Khachfe, Kiriakos, Kiriakos, Klein, Kohut, Kornhauser, Koutsomanis, Laffineur, Lagarde, Lalanne, Lannoy, Lapchin, Laprand, Laude, Leblanc, Lecieux, Leclerc, Le Couteulx, Ledent, Lefebvre, Lefiliatre, Legrand, Le Grix, Lelong, Leluyer, Lenaerts, Lepileur, Leplat, Lepoutre-Dujardin, Leroi, Leroy, Lesage, Lesage, Lesage, Lescanne-Darchis, Lescut, Lescut, Leurent, Levy, Lhermie, Lion, Lisambert, Loire, Louf, Louvet, Luciani, Lucidarme, Lugand, Macaigne, Maetz, Maillard, Mancheron, Manolache, Marks-Brunel, Marti, Martin, Martin, Marzloff, Mathurin, Mauillon, Maunoury, Maupas, Mesnard, Metayer, Methari, Meurisse, Meurisse, Michaud, Mirmaran, Modaine, Monthe, Morel, Mortier, Moulin, Mouterde, Mudry, Nachury, N'Guyen Khac, Notteghem, Ollevier, Ostyn, Ouraghi, Ouvry, Paillot, Panien-Claudot, Paoletti, Papazian, Parent, Pariente, Paris, Patrier, Paupart, Pauwels, Pauwels, Petit, Piat, Piotte, Plane, Plouvier, Pollet, Pommelet, Pop, Pordes, Pouchain, Prades, Prevost, Prevost, Quesnel, Queuniet, Quinton, Rabache, Rabelle, Raclot, Ratajczyk, Rault, Razemon, Reix, Revillon, Richez, Robinson, Rodriguez, Roger, Roux, Rudelli, Saber, Schlosseberg, Segrestin, Seguy, Serin, Seryer, Sevenet, Shekh, Silvie, Simon, Talbodec, Techy, Thelu, Thevenin, Thiebault, Thomas, Thorel, Tielman, Tode, Toisin, Tonnel, Touchais, Touze, Tranvouez, Triplet, Uhlen, Vaillant, Valmage, Vanco, Vandamme, Vanderbecq, Vander Eecken, Vandermolen, Vandevenne, Vandeville, Vandewalle, Vandewalle, Vaneslander, Vanhoove, Vanrenterghem, Varlet, Vasies, Verbiese, Vernier-Massouille, Vermelle, Verne, Vezilier-Cocq, Vigneron, Vincendet, Viot, Voiment, Wacrenier, Waeghemaecker, Wallez, Wantiez, Wartel, Weber, Willocquet, Wizla, Wolschies, Zalar, Zaouri, Zellweger, Ziade
      Pages: 1912 - 1917
      Abstract: ObjectiveNatural history of paediatric-onset ulcerative proctitis (UP) is poorly described. Our aim was to describe the phenotype and disease course of incident UP in a population-based study of paediatric-onset UC.Patients and methodsAll patients with UC diagnosed 2 years have been extracted from a population-based registry. UC location was defined according to the Paris classification. Cumulative risks for use of immunosuppressants (IS), anti-tumour necrosis factor alpha (TNF-α) therapy, colonic extension and colectomy were described using Kaplan-Meier method. Risk factors for colonic extension were assessed using Cox proportional hazards models.Results158 patients with paediatric-onset UC (91 females) with a median age at diagnosis of 14.5 years (Q1: 11.4–Q3: 16.1) have been identified and followed during a median of 11.4 years (8.2–15.8). Among them, 25% had UP (E1) at diagnosis and 49% of them presented a colonic extension at maximal follow-up. In these children, the cumulative risk for colonic extension was 10% at 1 year, 45% at 5 years and 52% at 10 years. No parameter at diagnosis was associated with colonic extension in the UP (E1 group). IS use was significantly lower in patients with UP than in those with E2, E3 or E4 location (p=0.049). For the UP cohort, the cumulative risk for colectomy was 3% at 1 year, 10% at 5 years, 13% at 10 years and 13% at 15 years. Risks for colonic extension, treatment with anti-TNF-α and colectomy did not differ between the E1 group and the E2–E3–E4 group.ConclusionsUP is frequent in paediatric-onset UC and should not be considered as a minor disease. Compared with more extensive UC locations, risks for colonic extension, anti-TNF-α therapy and colectomy were similar in UP, whereas the risk for use of IM was lower.
      PubDate: 2017-10-09T05:31:50-07:00
      DOI: 10.1136/gutjnl-2016-311970
      Issue No: Vol. 66, No. 11 (2017)
  • Anti-NKG2D monoclonal antibody (NNC0142-0002) in active Crohn's disease: a
           randomised controlled trial
    • Authors: Allez, M; Skolnick, B. E, Wisniewska-Jarosinska, M, Petryka, R, Overgaard, R. V, Van Assche, Ferrante, Petrunia, Peyrin-Biroulet, Cadiot, Dupas, Horvath, Kristof, Salamon, Schnabel, Varga, Avni, Konikoff, Lavy, Segol, Shirin, Mach, Rozciecha, Rydzewska, Alexeeva, Lenskaya, Osipenko, Simanenkov, Tkachev, Yakovlev, Barish, Epstein, Hardi, Pambianco, Poulos, Younes
      Pages: 1918 - 1925
      Abstract: ObjectiveAnti-NKG2D (NNC0142-0002) is an antagonising human immunoglobulin G4 monoclonal antibody that binds to natural killer group 2 member D (NKG2D) receptors, which are expressed by T cells and innate lymphoid cells, and may be linked to mucosal damage in Crohn's disease (CD).DesignSeventy-eight patients (aged ≥18 and ≤75 years) with CD for ≥3 months, Crohn's Disease Activity Index (CDAI) ≥220 and ≤450 and either C-reactive protein ≥10 mg/L or endoscopic evidence of inflammation, were randomised 1:1 to a single subcutaneous (SC) dose of 2 mg/kg anti-NKG2D or placebo. Primary endpoint was change in CDAI (CDAI) from baseline to week 4. Prespecified significance level was 10% for CDAI endpoints. A futility analysis was instituted due to slow recruitment.ResultsPrimary endpoint was not significantly different between anti-NKG2D and placebo (week 4 CDAI=–16); however, there was a significant difference by week 12 (CDAI=–55; p≤0.10). Significant improvements were noted in the non-failure to biologics subgroup (treated with anti-NKG2D (n=28)) from week 1 onward. Greater effects of anti-NKG2D were also observed in patients with baseline CDAI ≥330. Frequencies of adverse events (AEs) were comparable between anti-NKG2D and placebo. Most AEs were mild (49%) or moderate (43%). No antidrug antibodies were observed.ConclusionsA single SC dose of 2 mg/kg anti-NKG2D did not reduce disease activity at week 4 versus placebo, but the difference was significant at week 12, and effects were evident in key subgroups. These data support further development of anti-NKG2D in IBD.Trial registration numberNCT01203631.
      PubDate: 2017-10-09T05:31:50-07:00
      DOI: 10.1136/gutjnl-2016-311824
      Issue No: Vol. 66, No. 11 (2017)
  • A coding variant in FTO confers susceptibility to thiopurine-induced
           leukopenia in East Asian patients with IBD
    • Authors: Kim, H. S; Cheon, J. H, Jung, E. S, Park, J, Aum, S, Park, S. J, Eun, S, Lee, J, Rüther, U, Yeo, G. S. H, Ma, M, Park, K. S, Naito, T, Kakuta, Y, Lee, J. H, Kim, W. H, Lee, M. G.
      Pages: 1926 - 1935
      Abstract: ObjectiveMyelosuppression is a life-threatening complication of thiopurine therapy, and the incidence of thiopurine-induced myelosuppression is higher in East Asians than in Europeans. We investigated genetic factors associated with thiopurine-induced leukopenia in patients with IBD.DesignA genome-wide association study (GWAS) was conducted in thiopurine-treated patients with IBD, followed by high-throughput sequencing of genes identified as significant in the GWAS or those involved in thiopurine metabolism (n=331). Significant loci associated with thiopurine-induced leukopenia were validated in two additional replication cohorts (n=437 and n=330). Functional consequences of FTO (fat mass and obesity-associated) variant were examined both in vitro and in vivo.ResultsThe GWAS identified two loci associated with thiopurine-induced leukopenia (rs16957920, FTO intron; rs2834826, RUNX1 intergenic). High-throughput targeted sequencing indicated that an FTO coding variant (rs79206939, p.A134T) linked to rs16957920 is associated with thiopurine-induced leukopenia. This result was further validated in two replication cohorts (combined p=1.3x10–8, OR=4.3). The frequency of FTO p.A134T is 5.1% in Koreans but less than 0.1% in Western populations. The p.A134T variation reduced FTO activity by 65% in the nucleotide demethylase assay. In vivo experiments revealed that Fto–/– and Fto+/– mice were more susceptible to thiopurine-induced myelosuppression than wild-type mice.ConclusionsThe results suggest that the hypomorphic FTO p.A134T variant is associated with thiopurine-induced leukopenia. These results shed light on the novel physiological role of FTO and provide a potential pharmacogenetic biomarker for thiopurine therapy.
      PubDate: 2017-10-09T05:31:50-07:00
      DOI: 10.1136/gutjnl-2016-311921
      Issue No: Vol. 66, No. 11 (2017)
  • Blockade of {alpha}E{beta}7 integrin suppresses accumulation of CD8+ and
           Th9 lymphocytes from patients with IBD in the inflamed gut in vivo
    • Authors: Zundler, S; Schillinger, D, Fischer, A, Atreya, R, Lopez-Posadas, R, Watson, A, Neufert, C, Atreya, I, Neurath, M. F.
      Pages: 1936 - 1948
      Abstract: ObjectiveTherapeutically targeting lymphocyte adhesion is of increasing relevance in IBD. Yet, central aspects of the action of antiadhesion compounds are incompletely understood. We investigated the role of αEβ7 and α4β7 integrins and their blockade by vedolizumab and etrolizumab for trafficking of IBD T lymphocytes in an in vivo model of homing to and retention in the inflamed gut.DesignWe explored integrin expression in patients with IBD by flow cytometry and immunohistochemistry, while regulation of integrins was studied in T cell cultures. The functional relevance of integrins was assessed by adhesion assays and a recently established humanised mouse model in dextran sodium sulfate-treated immunodeficient mice.ResultsHigh expression of αEβ7 was noted on CD8+ and CD4+ Th9 cells, while α4β7 was expressed on CD8+, Th2 and Th17 cells. T cell receptor stimulation and transforming growth factor β were key inducers of αEβ7 on human T cells, while butyric acid suppressed αEβ7. In comparison to α4β7 blockade via vedolizumab, blockade of β7 via etrolizumab surrogate antibody superiorly reduced colonic numbers of CD8+ and Th9 cells in vivo after 3 hours, while no difference was noted after 0.5 hours. AEβ7 expression was higher on CD8+ T cells from patients with IBD under vedolizumab therapy.ConclusionsAEβ7 is of key relevance for gut trafficking of IBD CD8+ T cells and CD4+ Th9 cells in vivo and mainly retention might account for this effect. These findings indicate that blockade of αEβ7 in addition to α4β7 may be particularly effective in intestinal disorders with expansion of CD8+ and Th9 cells such as IBD.
      PubDate: 2017-10-09T05:31:50-07:00
      DOI: 10.1136/gutjnl-2016-312439
      Issue No: Vol. 66, No. 11 (2017)
  • Full-spectrum (FUSE) versus standard forward-viewing colonoscopy in an
           organised colorectal cancer screening programme
    • Authors: Hassan, C; Senore, C, Radaelli, F, De Pretis, G, Sassatelli, R, Arrigoni, A, Manes, G, Amato, A, Anderloni, A, Armelao, F, Mondardini, A, Spada, C, Omazzi, B, Cavina, M, Miori, G, Campanale, C, Sereni, G, Segnan, N, Repici, A.
      Pages: 1949 - 1955
      Abstract: ObjectiveMiss rate of polyps has been shown to be substantially lower with full-spectrum endoscopy (FUSE) compared with standard forward-viewing (SFV) colonoscopy in a tandem study at per polyp analysis. However, there is uncertainty on whether FUSE is also associated with a higher detection rate of colorectal neoplasia, especially advanced lesions, in per patient analysis.MethodsConsecutive subjects undergoing colonoscopy following a positive faecal immunochemical test (FIT) by experienced endoscopists and performed in the context of a regional colorectal cancer population-screening programme were randomised between colonoscopy with either FUSE or SFV colonoscopy in seven Italian centres. Randomisation was stratified by gender, age group and screening history. Primary outcomes included detection rates of advanced adenomas (A-ADR), adenomas (ADR) and sessile-serrated polyps (SSPDR).ResultsOf 741 eligible subjects, 658 were randomised to either FUSE (n=328) or SFV (n=330) colonoscopy and included in the analysis. Overall, 293/658 and 143/658 subjects had at least one adenoma (ADR 44.5%) and advanced adenoma (A-ADR 21.7%), respectively, while SSP was the most advanced lesion in 18 cases (SSPDR 2.7%). ADR and A-ADR were 43.6% and 19.5% in the FUSE arm, and 45.5% and 23.9% in the SFV arm, with no difference for both ADR (OR for FUSE: 0.96, 95% CI 0.81 to 1.14) and A-ADR (OR for FUSE: 0.82, 95% CI 0.61 to 1.09). No difference in SSPDR or multiplicity was detected between the two arms. In the per polyp analysis, the mean number of adenomas and proximal adenomas per patient was 0.81±1.25 and 0.47±0.93 in the FUSE arm, and 0.85±1.33 and 0.48±0.96 in the SFV colonoscopy arm (p=NS for both comparisons).ConclusionsNo statistically significant difference in ADR and A-ADR between FUSE and SFV colonoscopy was detected in a per patient analysis in FIT-positive patients.Trial registration numberISRCTN10357435.
      PubDate: 2017-10-09T05:31:50-07:00
      DOI: 10.1136/gutjnl-2016-311906
      Issue No: Vol. 66, No. 11 (2017)
  • Prebiotic galacto-oligosaccharides mitigate the adverse effects of iron
           fortification on the gut microbiome: a randomised controlled study in
           Kenyan infants
    • Authors: Paganini, D; Uyoga, M. A, Kortman, G. A. M, Cercamondi, C. I, Moretti, D, Barth-Jaeggi, T, Schwab, C, Boekhorst, J, Timmerman, H. M, Lacroix, C, Karanja, S, Zimmermann, M. B.
      Pages: 1956 - 1967
      Abstract: ObjectiveIron-containing micronutrient powders (MNPs) reduce anaemia in African infants, but the current high iron dose (12.5 mg/day) may decrease gut Bifidobacteriaceae and Lactobacillaceae, and increase enteropathogens, diarrhoea and respiratory tract infections (RTIs). We evaluated the efficacy and safety of a new MNP formula with prebiotic galacto-oligosaccharides (GOS) combined with a low dose (5 mg/day) of highly bioavailable iron.DesignIn a 4-month, controlled, double-blind trial, we randomised Kenyan infants aged 6.5–9.5 months (n=155) to receive daily (1) a MNP without iron (control); (2) the identical MNP but with 5 mg iron (2.5 mg as sodium iron ethylenediaminetetraacetate and 2.5 mg as ferrous fumarate) (Fe group); or (3) the identical MNP as the Fe group but with 7.5 g GOS (FeGOS group).ResultsAnaemia decreased by 50% in the Fe and FeGOS groups (p
      Keywords: Editor's choice, Gut
      PubDate: 2017-10-09T05:31:50-07:00
      DOI: 10.1136/gutjnl-2017-314418
      Issue No: Vol. 66, No. 11 (2017)
  • Prebiotic inulin-type fructans induce specific changes in the human gut
    • Authors: Vandeputte, D; Falony, G, Vieira-Silva, S, Wang, J, Sailer, M, Theis, S, Verbeke, K, Raes, J.
      Pages: 1968 - 1974
      Abstract: ObjectiveContrary to the long-standing prerequisite of inducing selective (ie, bifidogenic) effects, recent findings suggest that prebiotic interventions lead to ecosystem-wide microbiota shifts. Yet, a comprehensive characterisation of this process is still lacking. Here, we apply 16S rDNA microbiota profiling and matching (gas chromatography mass spectrometry) metabolomics to assess the consequences of inulin fermentation both on the composition of the colon bacterial ecosystem and faecal metabolites profiles.DesignFaecal samples collected during a double-blind, randomised, cross-over intervention study set up to assess the effect of inulin consumption on stool frequency in healthy adults with mild constipation were analysed. Faecal microbiota composition and metabolite profiles were linked to the study's clinical outcome as well as to quality-of-life measurements recorded.ResultsWhile faecal metabolite profiles were not significantly altered by inulin consumption, our analyses did detect a modest effect on global microbiota composition and specific inulin-induced changes in relative abundances of Anaerostipes, Bilophila and Bifidobacterium were identified. The observed decrease in Bilophila abundances following inulin consumption was associated with both softer stools and a favourable change in constipation-specific quality-of-life measures.ConclusionsEcosystem-wide analysis of the effect of a dietary intervention with prebiotic inulin-type fructans on the colon microbiota revealed that this effect is specifically associated with three genera, one of which (Bilophila) representing a promising novel target for mechanistic research.Trial registration numberNCT02548247.
      Keywords: Open access
      PubDate: 2017-10-09T05:31:50-07:00
      DOI: 10.1136/gutjnl-2016-313271
      Issue No: Vol. 66, No. 11 (2017)
  • A randomised comparison of two faecal immunochemical tests in
           population-based colorectal cancer screening
    • Authors: Grobbee, E. J; van der Vlugt, M, van Vuuren, A. J, Stroobants, A. K, Mundt, M. W, Spijker, W. J, Bongers, E. J. C, Kuipers, E. J, Lansdorp-Vogelaar, I, Bossuyt, P. M, Dekker, E, Spaander, M. C. W.
      Pages: 1975 - 1982
      Abstract: ObjectiveColorectal cancer screening programmes are implemented worldwide; many are based on faecal immunochemical testing (FIT). The aim of this study was to evaluate two frequently used FITs on participation, usability, positivity rate and diagnostic yield in population-based FIT screening.DesignComparison of two FITs was performed in a fourth round population-based FIT-screening cohort. Randomly selected individuals aged 50–74 were invited for FIT screening and were randomly allocated to receive an OC -Sensor (Eiken, Japan) or faecal occult blood (FOB)-Gold (Sentinel, Italy) test (March–December 2014). A cut-off of 10 µg haemoglobin (Hb)/g faeces (ie, 50 ng Hb/mL buffer for OC-Sensor and 59 ng Hb for FOB-Gold) was used for both FITs.ResultsIn total, 19 291 eligible invitees were included (median age 61, IQR 57–67; 48% males): 9669 invitees received OC-Sensor and 9622 FOB-Gold; both tests were returned by 63% of invitees (p=0.96). Tests were non-analysable in 0.7% of participants using OC-Sensor vs 2.0% using FOB-Gold (p
      PubDate: 2017-10-09T05:31:50-07:00
      DOI: 10.1136/gutjnl-2016-311819
      Issue No: Vol. 66, No. 11 (2017)
  • Race-dependent association of sulfidogenic bacteria with colorectal cancer
    • Authors: Yazici, C; Wolf, P. G, Kim, H, Cross, T.-W. L, Vermillion, K, Carroll, T, Augustus, G. J, Mutlu, E, Tussing-Humphreys, L, Braunschweig, C, Xicola, R. M, Jung, B, Llor, X, Ellis, N. A, Gaskins, H. R.
      Pages: 1983 - 1994
      Abstract: ObjectiveColorectal cancer (CRC) incidence is higher in African Americans (AAs) compared with non-Hispanic whites (NHWs). A diet high in animal protein and fat is an environmental risk factor for CRC development. The intestinal microbiota is postulated to modulate the effects of diet in promoting or preventing CRC. Hydrogen sulfide, produced by autochthonous sulfidogenic bacteria, triggers proinflammatory pathways and hyperproliferation, and is genotoxic. We hypothesised that sulfidogenic bacterial abundance in colonic mucosa may be an environmental CRC risk factor that distinguishes AA and NHW.DesignColonic biopsies from uninvolved or healthy mucosa from CRC cases and tumour-free controls were collected prospectively from five medical centres in Chicago for association studies. Sulfidogenic bacterial abundance in uninvolved colonic mucosa of AA and NHW CRC cases was compared with normal mucosa of AA and NHW controls. In addition, 16S rDNA sequencing was performed in AA cases and controls. Correlations were examined among bacterial targets, race, disease status and dietary intake.ResultsAAs harboured a greater abundance of sulfidogenic bacteria compared with NHWs regardless of disease status. Bilophila wadsworthia-specific dsrA was more abundant in AA cases than controls. Linear discriminant analysis of 16S rRNA gene sequences revealed five sulfidogenic genera that were more abundant in AA cases. Fat and protein intake and daily servings of meat were significantly higher in AAs compared with NHWs, and multiple dietary components correlated with a higher abundance of sulfidogenic bacteria.ConclusionsThese results implicate sulfidogenic bacteria as a potential environmental risk factor contributing to CRC development in AAs.
      PubDate: 2017-10-09T05:31:50-07:00
      DOI: 10.1136/gutjnl-2016-313321
      Issue No: Vol. 66, No. 11 (2017)
  • Epithelial NEMO/IKK{gamma} limits fibrosis and promotes regeneration
           during pancreatitis
    • Authors: Chan, L. K; Gerstenlauer, M, Konukiewitz, B, Steiger, K, Weichert, W, Wirth, T, Maier, H. J.
      Pages: 1995 - 2007
      Abstract: ObjectiveInhibitory B kinase (IKK)/nuclear factor B (NF-B) signalling has been implicated in the pathogenesis of pancreatitis, but its precise function has remained controversial. Here, we analyse the contribution of IKK/NF-B signalling in epithelial cells to the pathogenesis of pancreatitis by targeting the IKK subunit NF-B essential modulator (NEMO) (IKK), which is essential for canonical NF-B activation.DesignMice with a targeted deletion of NEMO in the pancreas were subjected to caerulein pancreatitis. Pancreata were examined at several time points and analysed for inflammation, fibrosis, cell death, cell proliferation, as well as cellular differentiation. Human samples were used to corroborate findings established in mice.ResultsIn acute pancreatitis, NEMO deletion in the pancreatic parenchyma resulted in minor changes during the early phase but led to the persistence of inflammatory and fibrotic foci in the recovery phase. In chronic pancreatitis, NEMO deletion aggravated inflammation and fibrosis, inhibited compensatory acinar cell proliferation, and enhanced acinar atrophy and acinar-ductal metaplasia. Gene expression analysis revealed sustained activation of profibrogenic genes and the CXCL12/CXCR4 axis in the absence of epithelial NEMO. In human chronic pancreatitis samples, the CXCL12/CXCR4 axis was activated as well, with CXCR4 expression correlating with the degree of fibrosis. The aggravating effects of NEMO deletion were attenuated by the administration of the CXCR4 antagonist AMD3100.ConclusionsOur results suggest that NEMO in epithelial cells exerts a protective effect during pancreatitis by limiting inflammation and fibrosis and improving acinar cell regeneration. The CXCL12/CXCR4 axis is an important mediator of that effect and may also be of importance in human chronic pancreatitis.
      PubDate: 2017-10-09T05:31:50-07:00
      DOI: 10.1136/gutjnl-2015-311028
      Issue No: Vol. 66, No. 11 (2017)
  • Efficacy and safety of sofosbuvir plus simeprevir therapy in Egyptian
           patients with chronic hepatitis C: a real-world experience
    • Authors: El-Khayat, H. R; Fouad, Y. M, Maher, M, El -Amin, H, Muhammed, H.
      Pages: 2008 - 2012
      Abstract: BackgroundSimeprevir plus sofosbuvir (SIM/SOF) regimen was recommended by professional guidelines for certain patients with HCV genotype 1 infection and there is lack of data about this regimen in patients with genotype 4 infection.AimTo evaluate the efficacy and safety of this regimen in Egyptian patients with chronic HCV genotype 4 infection in the real world.MethodsMulticentre observational study included 583 patients with HCV genotype 4 infection who began 12 weeks of treatment with SIM plus SOF. Demographic, clinical and virological data as well as adverse outcomes were collected. Treatment naïve patients were 342 (59%) of all included patients, 45% of patients had severe fibrosis (F3 and F4) while 55% had mild fibrosis (F1 and F2) and the primary outcome was sustained virological response (SVR).ResultsThe overall SVR rate was 95.7% (558 out of 583 patients). In total, SVR12 in naïve patients with mild fibrosis score (F1 and F2) was achieved in 98.9% (94/95) for F1 and 98.1% (105/107) for F2, while naïve patients with severe fibrosis (F3 and F4) achieved SVR of 97.7% (86/88) for F3 and (42/52) 80.8% for F4. SVR in patients with previous interferon treatment achieved in 100% (45/45) for patients with F1 and 98.7% (74/75) for F2. While 94.7% (72/76) in experienced patients with F3; and 88.9% (40/45) for F4 achieved SVR12. Notable side effects included rash in 21 patients, photosensitivity in 18 patients, pruritus in 44 patients and hyperbilirubinemia in 42 patients.ConclusionsA 12-week regimen of simeprevir/sofosbuvir was efficacious and well tolerated by treatment-naïve and treatment-experienced patients with chronic HCV genotype 4.
      PubDate: 2017-10-09T05:31:50-07:00
      DOI: 10.1136/gutjnl-2016-312012
      Issue No: Vol. 66, No. 11 (2017)
  • Erratum: Deletion of Men1 and somatostatin induces hypergastrinemia and
           gastric carcinoids
    • Pages: 2012 - 2012
      Abstract: Sundaresan S, Kang AJ, Hayes MM, et al. Deletion of Men1 and somatostatin induces hypergastrinemia and gastric carcinoids. Gut 2017;66:1012–21. In Figure 2, panels 2 D and E are duplicated images. The figure has been corrected :Figure 2
      Keywords: Gut
      PubDate: 2017-10-09T05:31:50-07:00
      DOI: 10.1136/gutjnl-2015-310928corr1
      Issue No: Vol. 66, No. 11 (2017)
  • Deep sequencing shows that HBV basal core promoter and precore variants
           reduce the likelihood of HBsAg loss following tenofovir disoproxil
           fumarate therapy in HBeAg-positive chronic hepatitis B
    • Authors: Bayliss, J; Yuen, L, Rosenberg, G, Wong, D, Littlejohn, M, Jackson, K, Gaggar, A, Kitrinos, K. M, Subramanian, G. M, Marcellin, P, Buti, M, Janssen, H. L. A, Gane, E, Sozzi, V, Colledge, D, Hammond, R, Edwards, R, Locarnini, S, Thompson, A, Revill, P. A.
      Pages: 2013 - 2023
      Abstract: ObjectiveHepatitis B e antigen (HBeAg) seroconversion and hepatitis B surface antigen (HBsAg) loss are important clinical outcomes for patients with chronic hepatitis B (CHB) treated with antiviral therapy. To date, there have been few studies that have evaluated viral sequence markers predicting serological response to nucleos(t)ide analogue (NA) treatment.DesignWe used next-generation sequencing (NGS) and quantitative HBV serology (HBeAg and HBsAg) to identify viral sequence markers associated with serological response to long-term tenofovir disoproxil fumarate therapy among HBeAg-positive patients. In the GS-US-174-0103 study, approximately half the patients seroconverted to anti-HBe by week 192 and 11% of patients exhibited HBsAg loss, the closest outcome to functional cure. The frequency of HBV variants that have previously been associated with HBV clinical outcomes was evaluated. HBV viral diversity in baseline sequences generated by NGS was calculated using Shannon entropy.ResultsNGS analysis of HBV sequences from 157 patients infected with genotypes A to D showed the frequency of variants in the basal core promoter (BCP) and precore (PC) regions varied by genotype and that these mutations were associated with the absence of HBsAg loss. This was the case even when mutations were present at frequencies below the threshold of detection by population sequencing. Increased viral diversity across the HBV genome as determined by NGS was also associated with reduced likelihood of HBsAg loss.ConclusionPatients with detectable BCP and/or PC variants and higher viral diversity have a lower probability of HBsAg loss during long-term NA therapy. Strategies to achieve functional cure of HBV infection through combination therapy should consider using NGS to stratify patients according to BCP/PC sequence. Consideration should also be given to earlier initiation of therapy prior to the emergence of BCP/PC variants.Trial registration numberNCT00116805; Post result.
      PubDate: 2017-10-09T05:31:50-07:00
      DOI: 10.1136/gutjnl-2015-309300
      Issue No: Vol. 66, No. 11 (2017)
  • Acute pancreatitis: recent advances through randomised trials
    • Authors: van Dijk, S. M; Hallensleben, N. D. L, van Santvoort, H. C, Fockens, P, van Goor, H, Bruno, M. J, Besselink, M. G, for the Dutch Pancreatitis Study Group
      Pages: 2024 - 2032
      Abstract: Acute pancreatitis is one of the most common GI conditions requiring acute hospitalisation and has a rising incidence. In recent years, important insights on the management of acute pancreatitis have been obtained through numerous randomised controlled trials. Based on this evidence, the treatment of acute pancreatitis has gradually developed towards a tailored, multidisciplinary effort, with distinctive roles for gastroenterologists, radiologists and surgeons. This review summarises how to diagnose, classify and manage patients with acute pancreatitis, emphasising the evidence obtained through randomised controlled trials.
      Keywords: GUT Recent advances in clinical practice, Gut
      PubDate: 2017-10-09T05:31:50-07:00
      DOI: 10.1136/gutjnl-2016-313595
      Issue No: Vol. 66, No. 11 (2017)
  • GI highlights from the literature
    • Authors: McLean; M. H.
      Pages: 2033 - 2034
      Abstract: Basic scienceTh17 cells; friend or foe in intestinal homeostasis' Hegazy AN, West NR, Stubbington MJT, et al. Circulating and tissue-resident CD4+ T cells with reactivity to intestinal microbiota are abundant in healthy individuals and function is altered during inflammation. Gastroenterology 2017 Aug. pii: S0016-5085(17)35979-6. doi: 10.1053/j.gastro.2017.07.047. (Epub ahead of print). Intestinal immune responses are tightly regulated to provide the necessary protection against pathogenic organisms while controlling responses to commensal species. Characterising T cell responses to bacteria is an important aspect of the puzzle. In humans, circulating memory T cells recognise peptides derived from gut bacteria and can cross-react to pathogens. While the process may be beneficial during homeostasis, this potentially contributes to inflammatory conditions such as IBD when regulatory aspects are dysfunctional. Currently, there is a lack of knowledge regarding the type, frequency and functional phenotype of T cells that react to intestinal microbes in the gut and...
      Keywords: Gut
      PubDate: 2017-10-09T05:31:50-07:00
      DOI: 10.1136/gutjnl-2017-315186
      Issue No: Vol. 66, No. 11 (2017)
  • Haemoglobin decline before coeliac disease diagnosis: a nationwide
           transfusion cohort study of 1.1 million blood donors
    • Authors: Ludvigsson, J. F; Sjölander, A, Murray, J. A, Hjalgrim, H, Edgren, G.
      Pages: 2036 - 2037
      Abstract: The recent British Society of Gastroenterology guidelines for the management and diagnosis of coeliac disease (CD) suggests that individuals with iron-deficiency anaemia be tested for CD.1 We have previously shown that decreasing haemoglobin (Hb) levels precede diagnosis of a number of malignancies, including most GI and haematological malignancies.2 If Hb levels begin to decline prior to CD diagnosis, this may provide a means to estimate the duration from disease onset to diagnosis. We therefore set up a case-control study to examine Hb concentration before CD diagnosis using a similar approach as in a previous study.2 We first linked data on Hb concentration measured repeatedly for 1.1 million blood donors in the Swedish portion of the Scandinavian Donations and Transfusions database 2,3 with a nationwide histopathology database providing diagnosis of villous atrophy (ie, CD).4 We then identified 1567 donors diagnosed...
      PubDate: 2017-10-09T05:31:50-07:00
      DOI: 10.1136/gutjnl-2016-313541
      Issue No: Vol. 66, No. 11 (2017)
  • Interleukin 13-mediated colitis in the absence of IL-4R{alpha} signalling
    • Authors: Hoving, J. C; Cutler, A. J, Leeto, M, Horsnell, W. G. C, Dewals, B. G, Nieuwenhuizen, N. E, Brombacher, F.
      Pages: 2037 - 2039
      Abstract: Sufficient evidence points to interleukin 13 (IL-13) as an important pathological factor in UC and raises hopes to a promising new treatment strategy.1–3 However, the outcomes of two recent clinical trials, both published in Gut 2015, suggest otherwise.4 5 A commentary published in the same issue described these results as crushing the enthusiasm for anti-IL-13 treatment in UC.6 In this letter, we show evidence that the disease outcome is determined by the type of signalling pathway used by IL-13 in mice. Therefore, we suggest that directly blocking IL-13 remains a potential treatment strategy for a subset of patients with UC that have elevated tissue IL-13 production. In the first clinical study using anrukinzumab treatment, which targets the IL-4 receptor-alpha (IL-4Rα) and not IL-13 directly, had no effect on improving the clinical response or remission rates of patients...
      PubDate: 2017-10-09T05:31:50-07:00
      DOI: 10.1136/gutjnl-2016-313208
      Issue No: Vol. 66, No. 11 (2017)
  • No difference in emergency department visits before and after transition
           for coeliac disease
    • Authors: Reilly, N. R; Green, P. H. R, Ludvigsson, J. F.
      Pages: 2039 - 2040
      Abstract: In a recent consensus document, we and others presented recommendations for the transition of care from childhood to adulthood in coeliac disease (CD).1 Models of care transition share a goal of prevention of medical care lapses. Lower continuity of general paediatric care has been associated with greater risk of emergency department (ED) visits and hospitalisation.2 Yet patient vulnerability during and immediately following transition may be under-recognised. Poorer medical adherence has been noted for young adults with chronic illnesses during their transition to adult care.3 4 In a US study, ED visits comprised over 20% of the medical care of young adults, a significantly greater proportion than in other age groups.5 Young adults with sickle cell disease in the midst of transition to adult care had more ED visits when compared with those with stable paediatric care or who were...
      PubDate: 2017-10-09T05:31:50-07:00
      DOI: 10.1136/gutjnl-2017-313882
      Issue No: Vol. 66, No. 11 (2017)
  • Activation of protease-activated receptor 4 of mast cells could
           downregulate proinflammatory cytokines in irritable bowel syndrome
    • Authors: An, S; Zong, G, Wang, Z, Shi, J, Du, H, Hu, J.
      Pages: 2040 - 2042
      Abstract: We read with interest the article by Wouters et al1 on mast cells (MCs) that dominate the mucosal inflammatory infiltrate in the intestine of functional GI disorders (FGIDs). Protease-activated receptor 4 (PAR4) is extensively expressed in MCs in allergic inflammation2 and may mediate an antinociceptive effect in gut visceral hyperalgesia.3 We wish to report the potential influence of PAR4 activation on the production of cytokines from MCs that might regulate sensitisation and subsequent heightened pain behaviour in FGIDs.4 5 Immunoreactivity for tryptase and PAR4 was analysed in the colonic mucosa of 21 patients with IBS with diarrhoea (IBS-D) and 16 healthy controls (figure 1A, B). Numbers of MCs were obtained by counting tryptase-immunoreactive cells. There were substantial increases in the numbers of both tryptase and PAR4-positive cells seen in IBS-D colonic mucosa compared with those in healthy...
      PubDate: 2017-10-09T05:31:50-07:00
      DOI: 10.1136/gutjnl-2016-313504
      Issue No: Vol. 66, No. 11 (2017)
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Heriot-Watt University
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