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Gut
Journal Prestige (SJR): 7.44
Citation Impact (citeScore): 10
Number of Followers: 243  
 
  Hybrid Journal Hybrid journal (It can contain Open Access articles)
ISSN (Print) 0017-5749 - ISSN (Online) 1468-3288
Published by BMJ Publishing Group Homepage  [68 journals]
  • Challenges and opportunities for IBD drug development: from early stage to
           regulatory approval
    • Authors: Danese, S; Schabel, E, Ainsworth, M. A, Peyrin-Biroulet, L.
      Pages: 1157 - 1161
      Abstract: Introduction Increased understanding of the immunopathology of inflammatory bowel disease (IBD) has resulted in the development of novel therapies such as vedolizumab or ustekinumab, and the investigation of new agents including Janus kinase inhibitors, anti-mucosal vascular addressin cell adhesion molecule-1 agents, anti-interleukin-12/23 monoclonal antibody and sphingosine-1-phosphate receptor-1 selective agonists.1 Over the last years, new approaches to mentoring drug research and testing have been developed. Among these methods, the fast-track drug designation and subsequent approval of safe regimens represent an emerging drug development approach in IBD treatment.2 Since 2001, the European Commission has started a fast-track approval programme for the European Medicines Agency (EMA). The Committee for Human Medicinal Products, established under the EMA, is responsible for such an accelerated review process.2 The requirements and time frames for approval of a drug under the accelerated review process are similar to those used by...
      Keywords: Gut
      PubDate: 2020-06-06T02:47:05-07:00
      DOI: 10.1136/gutjnl-2019-320542
      Issue No: Vol. 69, No. 7 (2020)
       
  • Unusual cystic lesion adjacent to the stomach
    • Authors: McGoran, J. J; Mullineux, J. H, Sutton, C. D, Kadri, S. R.
      Pages: 1161 - 1293
      Abstract: Introduction A 47-year-old woman with suspected hypertrophic cardiomyopathy underwent a cardiac MRI, which detected the presence of an incidental cystic lesion adjacent to the upper GI tract. She was asymptomatic from a GI viewpoint, and her case was discussed in the multidisciplinary team meeting after a CT scan supported the incidental finding (figure 1A and B). The recommendation of the team, supported by the wishes of the patient, was that she would undergo endoscopic ultrasound (EUS) examination and contents aspiration of this abnormality to gain greater clarification. Gastroscopy and linear EUS examination of the stomach detected a cystic mass, surrounded by muscularis propria, measuring a maximal diameter of 30 mm in the upper corpus (figure 1C). Aspiration of the contents was performed, eliciting a thick fluid that was sent for cytological analysis. The fluid was also tested using pH indicator paper and was shown to...
      Keywords: GUT Snapshot, Gut
      PubDate: 2020-06-06T02:47:05-07:00
      DOI: 10.1136/gutjnl-2019-318823
      Issue No: Vol. 69, No. 7 (2020)
       
  • Hepatitis D virus: is it all in the family'
    • Authors: Boyd, A; Wandeler, G.
      Pages: 1162 - 1163
      Abstract: Hepatitis delta virus (HDV) infection is the most severe form of chronic viral hepatitis: HDV-infected individuals are more likely to die from advanced liver disease compared with hepatitis B virus (HBV)-infected without HDV and their risk of developing hepatocellular carcinoma is up to nine times higher.1 HDV is a defective virus, using the HBV surface antigen to enter hepatocytes. Pegylated interferon-alfa is currently the only recommended therapy for HDV infection, although treatment success remains unacceptably low. The recent development of novel treatments, including the entry inhibitor bulevirtide, may improve treatment outcomes. Thus, understanding the epidemiology of HDV is crucial for planning and implementing efficient testing and management strategies. According to a recent meta-analysis, HDV infection, as determined by the presence of anti-HDV antibodies, affects 7% of HBV-infected persons in sub-Saharan Africa (SSA), with a pooled prevalence reaching 26% of general hepatitis B surface antigen (HBsAg)-positive individuals in...
      Keywords: Gut
      PubDate: 2020-06-06T02:47:05-07:00
      DOI: 10.1136/gutjnl-2019-320549
      Issue No: Vol. 69, No. 7 (2020)
       
  • Non-invasive diagnosis of patients with 'at-risk NAFLD : only fibrosis
           counts'
    • Authors: Geier, A; Boursier, J.
      Pages: 1164 - 1165
      Abstract: In Gut, Loomba and Adams refer to the recent advances in non-invasive assessment of hepatic fibrosis.1 Not surprisingly, many recent studies in the field were conducted in patients at risk or with clinically diagnosed non-alcoholic fatty liver disease (NAFLD). The implications of non-invasive testing are particularly far reaching in this group of patients since this disease affects 25% of Western populations. The principal need to identify the small subset of NAFLD patients at-risk of progressive disease and liver-related outcomes is obvious. Recent retrospective longitudinal studies have shown that non-alcoholic steatohepatitis (NASH) is not an independent predictor of liver-related complication or mortality in NAFLD.2 3 NASH is a risk factor of fibrosis progression rather than an immediate risk of liver related complication and therefore positions at a lower prognostic significance in the hierarchical model of NAFLD.4 The diagnosis of NASH still requires...
      Keywords: Gut
      PubDate: 2020-06-06T02:47:05-07:00
      DOI: 10.1136/gutjnl-2020-320785
      Issue No: Vol. 69, No. 7 (2020)
       
  • New role for azathioprine in case of switching anti-TNFs in IBD
    • Authors: Papamichael, K; Cheifetz, A. S, Irving, P. M.
      Pages: 1165 - 1167
      Abstract: Antitumour necrosis factor (anti-TNF) therapy has revolutionised the treatment of moderate to severe inflammatory bowel disease (IBD). However, up to 30% of patients with Crohn’s disease (CD) and ulcerative colitis (UC) do not respond to anti-TNF therapy, often referred to as primary non-responders. Additionally, almost 50% of patients who initially respond to anti-TNF lose response over time, a phenomenon known as secondary loss of response (SLR).1 Both of these negative outcomes are most commonly caused by pharmacokinetic issues characterised by undetectable or low drug concentrations due to increased clearance with or without the presence of antidrug antibodies (ADA), so-called immunogenicity.2 The recent prospective The Personalised Anti-TNF therapy in Crohn’s Disease Study (PANTS) study showed that for both infliximab and adalimumab, suboptimal week 14 drug concentrations predicted immunogenicity, and the development of ADA predicted subsequent low drug concentrations.3 Immunogenicity may account for at least...
      Keywords: Gut
      PubDate: 2020-06-06T02:47:05-07:00
      DOI: 10.1136/gutjnl-2020-320677
      Issue No: Vol. 69, No. 7 (2020)
       
  • Mediterranean diet, gut microbiota and health: when age and calories do
           not add up!
    • Authors: Cani, P. D; Van Hul, M.
      Pages: 1167 - 1168
      Abstract: A healthy diet is generally recognised as a diet that supports the physiological and energetic requirements of the body and provides sufficient, though not excessive, amounts of micronutrients and macronutrients. Despite this self-evident definition, the implementation of this basic principle has proven very difficult in modern western society. The benefits of adopting a Mediterranean diet (MedDiet) were already scientifically described more than 50 years ago,1 when a reduction in cardiovascular disease risk was observed among populations whose nutritional habits were consistent with those of people from the Mediterranean basin.2 Today, adherence to a MedDiet has been associated with lower mortality, reductions in obesity, type 2 diabetes, low-grade inflammation, cancer, Alzheimer’s disease and depression, and, more recently, the delayed onset of Crohn’s disease.3–5 Surprisingly, the exact mechanisms of action are not yet fully understood, and various hypotheses have been proposed...
      Keywords: Open access, Gut
      PubDate: 2020-06-06T02:47:05-07:00
      DOI: 10.1136/gutjnl-2020-320781
      Issue No: Vol. 69, No. 7 (2020)
       
  • Detection of Barretts oesophagus through exhaled breath using an
           electronic nose device
    • Authors: Peters, Y; Schrauwen, R. W. M, Tan, A. C, Bogers, S. K, de Jong, B, Siersema, P. D.
      Pages: 1169 - 1172
      Abstract: Timely detection of oesophageal adenocarcinoma (OAC) and even more so its precursor Barrett’s oesophagus (BO) could contribute to decrease OAC incidence and mortality. An accurate, minimally-invasive screening method for BO for widespread use is currently not available. In a proof-of-principle study in 402 patients, we developed and cross-validated a BO prediction model using volatile organic compounds (VOCs) analysis with an electronic nose device. This electronic nose was able to distinguish between patients with and without BO with good diagnostic accuracy (sensitivity 91% specificity 74%) and seemed to be independent of proton pump inhibitor use, the presence of hiatal hernia, and reflux. This technique may enable an efficient, well-tolerated, and sensitive and specific screening method to select high-risk individuals to undergo upper endoscopy.
      Keywords: Press releases, Gut
      PubDate: 2020-06-06T02:47:05-07:00
      DOI: 10.1136/gutjnl-2019-320273
      Issue No: Vol. 69, No. 7 (2020)
       
  • Transjugular intrahepatic portosystemic stent-shunt in the management of
           portal hypertension
    • Authors: Tripathi, D; Stanley, A. J, Hayes, P. C, Travis, S, Armstrong, M. J, Tsochatzis, E. A, Rowe, I. A, Roslund, N, Ireland, H, Lomax, M, Leithead, J. A, Mehrzad, H, Aspinall, R. J, McDonagh, J, Patch, D.
      Pages: 1173 - 1192
      Abstract: These guidelines on transjugular intrahepatic portosystemic stent-shunt (TIPSS) in the management of portal hypertension have been commissioned by the Clinical Services and Standards Committee (CSSC) of the British Society of Gastroenterology (BSG) under the auspices of the Liver Section of the BSG. The guidelines are new and have been produced in collaboration with the British Society of Interventional Radiology (BSIR) and British Association of the Study of the Liver (BASL). The guidelines development group comprises elected members of the BSG Liver Section, representation from BASL, a nursing representative and two patient representatives. The quality of evidence and grading of recommendations was appraised using the GRADE system. These guidelines are aimed at healthcare professionals considering referring a patient for a TIPSS. They comprise the following subheadings: indications; patient selection; procedural details; complications; and research agenda. They are not designed to address: the management of the underlying liver disease; the role of TIPSS in children; or complex technical and procedural aspects of TIPSS.
      Keywords: Open access, Gut
      PubDate: 2020-06-06T02:47:05-07:00
      DOI: 10.1136/gutjnl-2019-320221
      Issue No: Vol. 69, No. 7 (2020)
       
  • METTL3-mediated m6A modification of HDGF mRNA promotes gastric cancer
           progression and has prognostic significance
    • Authors: Wang, Q; Chen, C, Ding, Q, Zhao, Y, Wang, Z, Chen, J, Jiang, Z, Zhang, Y, Xu, G, Zhang, J, Zhou, J, Sun, B, Zou, X, Wang, S.
      Pages: 1193 - 1205
      Abstract: ObjectiveN6-methyladenosine (m6A) RNA methylation and its associated methyltransferase METTL3 are involved in tumour initiation and progression via the regulation of RNA function. This study explored the biological function and clinical significance of METTL3 in gastric cancer (GC).DesignThe prognostic value of METTL3 expression was evaluated using tissue microarray and immunohistochemical staining analyses in a human GC cohort. The biological role and mechanism of METTL3 in GC tumour growth and liver metastasis were determined in vitro and in vivo.ResultsThe level of m6A RNA was significantly increased in GC, and METTL3 was the main regulator involved in the abundant m6A RNA modification. METTL3 expression was significantly elevated in GC tissues and associated with poor prognosis. Multivariate Cox regression analysis revealed that METTL3 expression was an independent prognostic factor and effective predictor in human patients with GC. Moreover, METTL3 overexpression promoted GC proliferation and liver metastasis in vitro and in vivo. Mechanistically, P300-mediated H3K27 acetylation activation in the promoter of METTL3 induced METTL3 transcription, which stimulated m6A modification of HDGF mRNA, and the m6A reader IGF2BP3 then directly recognised and bound to the m6A site on HDGF mRNA and enhanced HDGF mRNA stability. Secreted HDGF promoted tumour angiogenesis, while nuclear HDGF activated GLUT4 and ENO2 expression, followed by an increase in glycolysis in GC cells, which was correlated with subsequent tumour growth and liver metastasis.ConclusionsElevated METTL3 expression promotes tumour angiogenesis and glycolysis in GC, indicating that METTL3 expression is a potential prognostic biomarker and therapeutic target for human GC.
      Keywords: Gut
      PubDate: 2020-06-06T02:47:05-07:00
      DOI: 10.1136/gutjnl-2019-319639
      Issue No: Vol. 69, No. 7 (2020)
       
  • Addition of azathioprine to the switch of anti-TNF in patients with IBD in
           clinical relapse with undetectable anti-TNF trough levels and antidrug
           antibodies: a prospective randomised trial
    • Authors: Roblin, X; Williet, N, Boschetti, G, Phelip, J.-M, Del Tedesco, E, Berger, A.-E, Vedrines, P, Duru, G, Peyrin-Biroulet, L, Nancey, S, Flourie, B, Paul, S.
      Pages: 1206 - 1212
      Abstract: ObjectivesIn patients with IBD experiencing an immune-mediated loss of response (LOR) to antitumour necrosis factor (anti-TNF), algorithms recommend a switch of anti-TNF without immunosuppressive drug. The aim of our study was to compare in these patients two strategies: either switch to a second anti-TNF alone or with addition of azathioprine (AZA). After randomisation outcomes (time to clinical and pharmacokinetic failure) were compared between the two groups during a 2-year follow-up period.DesignConsecutive IBD patients in immune-mediated LOR to a first optimised anti-TNF given in monotherapy were randomised to receive either AZA or nothing with induction by a second anti-TNF in both arms. Clinical failure was defined for Crohn’s disease (CD) as a Harvey-Bradshaw index ≥5 associated with a faecal calprotectin level>250 µg/g stool and for UC as a Mayo score>5 with endoscopic subscore>1 or as the occurrence of adverse events requiring to stop treatment. Unfavourable pharmacokinetics of the second anti-TNF were defined by the appearance of undetectable trough levels of anti-TNF with high antibodies (drug-sensitive assay) or by that of antibodies (drug-tolerant assay).ResultsNinety patients (48 CDs) were included, and 45 of them received AZA after randomisation. The second anti-TNF was adalimumab or infliximab in 40 and 50 patients, respectively. Rates of clinical failure and occurrence of unfavourable pharmacokinetics were higher in monotherapy compared with combination therapy (p24 months). At 24 months, survival rates without clinical failure and without appearance of unfavourable pharmacokinetics were respectively 22 versus 77% and 22% versus 78% (p
      Keywords: Gut
      PubDate: 2020-06-06T02:47:05-07:00
      DOI: 10.1136/gutjnl-2019-319758
      Issue No: Vol. 69, No. 7 (2020)
       
  • Outcomes of COVID-19 in 79 patients with IBD in Italy: an IG-IBD study
    • Authors: Bezzio, C; Saibeni, S, Variola, A, Allocca, M, Massari, A, Gerardi, V, Casini, V, Ricci, C, Zingone, F, Amato, A, Caprioli, F, Lenti, M. V, Vigano, C, Ascolani, M, Bossa, F, Castiglione, F, Cortelezzi, C, Grossi, L, Milla, M, Morganti, D, Pastorelli, L, Ribaldone, D. G, Sartini, A, Soriano, A, Manes, G, Danese, S, Fantini, M, Armuzzi, A, Daperno, M, Fiorino, G, on behalf of Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD)
      Pages: 1213 - 1217
      Abstract: ObjectivesCOVID-19 has rapidly become a major health emergency worldwide. Patients with IBD are at increased risk of infection, especially when they have active disease and are taking immunosuppressive therapy. The characteristics and outcomes of COVID-19 in patients with IBD remain unclear.DesignThis Italian prospective observational cohort study enrolled consecutive patients with an established IBD diagnosis and confirmed COVID-19. Data regarding age, sex, IBD (type, treatments and clinical activity), other comorbidities (Charlson Comorbidity Index (CCI)), signs and symptoms of COVID-19 and therapies were compared with COVID-19 outcomes (pneumonia, hospitalisation, respiratory therapy and death).ResultsBetween 11 and 29 March 2020, 79 patients with IBD with COVID-19 were enrolled at 24 IBD referral units. Thirty-six patients had COVID-19-related pneumonia (46%), 22 (28%) were hospitalised, 7 (9%) required non-mechanical ventilation, 9 (11%) required continuous positive airway pressure therapy, 2 (3%) had endotracheal intubation and 6 (8%) died. Four patients (6%) were diagnosed with COVID-19 while they were being hospitalised for a severe flare of IBD. Age over 65 years (p=0.03), UC diagnosis (p=0.03), IBD activity (p=0.003) and a CCI score>1 (p=0.04) were significantly associated with COVID-19 pneumonia, whereas concomitant IBD treatments were not. Age over 65 years (p=0.002), active IBD (p=0.02) and higher CCI score were significantly associated with COVID-19-related death.ConclusionsActive IBD, old age and comorbidities were associated with a negative COVID-19 outcome, whereas IBD treatments were not. Preventing acute IBD flares may avoid fatal COVID-19 in patients with IBD. Further research is needed.
      Keywords: Gut, COVID-19
      PubDate: 2020-06-06T02:47:05-07:00
      DOI: 10.1136/gutjnl-2020-321411
      Issue No: Vol. 69, No. 7 (2020)
       
  • Mediterranean diet intervention alters the gut microbiome in older people
           reducing frailty and improving health status: the NU-AGE 1-year dietary
           intervention across five European countries
    • Authors: Ghosh, T. S; Rampelli, S, Jeffery, I. B, Santoro, A, Neto, M, Capri, M, Giampieri, E, Jennings, A, Candela, M, Turroni, S, Zoetendal, E. G, Hermes, G. D. A, Elodie, C, Meunier, N, Brugere, C. M, Pujos-Guillot, E, Berendsen, A. M, De Groot, L. C. P. G. M, Feskins, E. J. M, Kaluza, J, Pietruszka, B, Bielak, M. J, Comte, B, Maijo-Ferre, M, Nicoletti, C, De Vos, W. M, Fairweather-Tait, S, Cassidy, A, Brigidi, P, Franceschi, C, O'Toole, P. W.
      Pages: 1218 - 1228
      Abstract: ObjectiveAgeing is accompanied by deterioration of multiple bodily functions and inflammation, which collectively contribute to frailty. We and others have shown that frailty co-varies with alterations in the gut microbiota in a manner accelerated by consumption of a restricted diversity diet. The Mediterranean diet (MedDiet) is associated with health. In the NU-AGE project, we investigated if a 1-year MedDiet intervention could alter the gut microbiota and reduce frailty.DesignWe profiled the gut microbiota in 612 non-frail or pre-frail subjects across five European countries (UK, France, Netherlands, Italy and Poland) before and after the administration of a 12-month long MedDiet intervention tailored to elderly subjects (NU-AGE diet).ResultsAdherence to the diet was associated with specific microbiome alterations. Taxa enriched by adherence to the diet were positively associated with several markers of lower frailty and improved cognitive function, and negatively associated with inflammatory markers including C-reactive protein and interleukin-17. Analysis of the inferred microbial metabolite profiles indicated that the diet-modulated microbiome change was associated with an increase in short/branch chained fatty acid production and lower production of secondary bile acids, p-cresols, ethanol and carbon dioxide. Microbiome ecosystem network analysis showed that the bacterial taxa that responded positively to the MedDiet intervention occupy keystone interaction positions, whereas frailty-associated taxa are peripheral in the networks.ConclusionCollectively, our findings support the feasibility of improving the habitual diet to modulate the gut microbiota which in turn has the potential to promote healthier ageing.
      Keywords: Open access, Editor's choice, Gut
      PubDate: 2020-06-06T02:47:05-07:00
      DOI: 10.1136/gutjnl-2019-319654
      Issue No: Vol. 69, No. 7 (2020)
       
  • Gut microbiota of obese subjects with Prader-Willi syndrome is linked to
           metabolic health
    • Authors: Olsson, L. M; Poitou, C, Tremaroli, V, Coupaye, M, Aron-Wisnewsky, J, Bäckhed, F, Clement, K, Caesar, R.
      Pages: 1229 - 1238
      Abstract: ObjectiveThe gut microbiota has been implicated in the aetiology of obesity and associated comorbidities. Patients with Prader-Willi syndrome (PWS) are obese but partly protected against insulin resistance. We hypothesised that the gut microbiota of PWS patients differs from that of non-genetically obese controls and correlate to metabolic health. Therefore, here we used PWS as a model to study the role of gut microbiota in the prevention of metabolic complications linked to obesity.DesignWe conducted a case-control study with 17 adult PWS patients and 17 obese subjects matched for body fat mass index, gender and age. The subjects were metabolically characterised and faecal microbiota was profiled by 16S ribosomal RNA gene sequencing. The patients’ parents were used as a non-obese control group. Stool samples from two PWS patients and two obese controls were used for faecal microbiota transplantations in germ-free mice to examine the impact of the microbiota on glucose metabolism.ResultsThe composition of the faecal microbiota in patients with PWS differed from that of obese controls, and was characterised by higher phylogenetic diversity and increased abundance of several taxa such as Akkermansia, Desulfovibrio and Archaea, and decreased abundance of Dorea. Microbial taxa prevalent in the PWS microbiota were associated with markers of insulin sensitivity. Improved insulin resistance of PWS was partly transmitted by faecal microbiota transplantations into germ-free mice.ConclusionThe gut microbiota of PWS patients is similar to that of their non-obese parents and might play a role for the protection of PWS patients from metabolic complications.
      Keywords: Open access, Gut
      PubDate: 2020-06-06T02:47:05-07:00
      DOI: 10.1136/gutjnl-2019-319322
      Issue No: Vol. 69, No. 7 (2020)
       
  • Myristoleic acid produced by enterococci reduces obesity through brown
           adipose tissue activation
    • Authors: Quan, L.-H; Zhang, C, Dong, M, Jiang, J, Xu, H, Yan, C, Liu, X, Zhou, H, Zhang, H, Chen, L, Zhong, F.-L, Luo, Z.-B, Lam, S.-M, Shui, G, Li, D, Jin, W.
      Pages: 1239 - 1247
      Abstract: ObjectiveDietary fibre has beneficial effects on energy metabolism, and the majority of studies have focused on short-chain fatty acids produced by gut microbiota. Ginseng has been reported to aid in body weight management, however, its mechanism of action is not yet clear. In this study, we focused on the potential modulating effect of ginseng on gut microbiota, aiming to identify specific strains and their metabolites, especially long-chain fatty acids (LCFA), which mediate the anti-obesity effects of ginseng.DesignDb/db mice were gavaged with ginseng extract (GE) and the effects of GE on gut microbiota were evaluated using 16S rDNA-based high throughput sequencing. To confirm the candidate fatty acids, untargeted metabolomics analyses of the serum and medium samples were performed.ResultsWe demonstrated that GE can induce Enterococcus faecalis, which can produce an unsaturated LCFA, myristoleic acid (MA). Our results indicate that E. faecalis and its metabolite MA can reduce adiposity by brown adipose tissue (BAT) activation and beige fat formation. In addition, the gene of E. faecalis encoding Acyl-CoA thioesterases (ACOTs) exhibited the biosynthetic potential to synthesise MA, as knockdown (KD) of the ACOT gene by CRISPR-dCas9 significantly reduced MA production. Furthermore, exogenous treatment with KD E. faecalis could not reproduce the beneficial effects of wild type E. faecalis, which work by augmenting the circulating MA levels.ConclusionsOur results demonstrated that the gut microbiota-LCFA-BAT axis plays an important role in host metabolism, which may provide a strategic advantage for the next generation of anti-obesity drug development.
      Keywords: Gut
      PubDate: 2020-06-06T02:47:05-07:00
      DOI: 10.1136/gutjnl-2019-319114
      Issue No: Vol. 69, No. 7 (2020)
       
  • A novel faecal Lachnoclostridium marker for the non-invasive diagnosis of
           colorectal adenoma and cancer
    • Authors: Liang, J. Q; Li, T, Nakatsu, G, Chen, Y.-X, Yau, T. O, Chu, E, Wong, S, Szeto, C. H, Ng, S. C, Chan, F. K. L, Fang, J.-Y, Sung, J. J. Y, Yu, J.
      Pages: 1248 - 1257
      Abstract: ObjectiveThere is a need for early detection of colorectal cancer (CRC) at precancerous-stage adenoma. Here, we identified novel faecal bacterial markers for diagnosing adenoma.DesignThis study included 1012 subjects (274 CRC, 353 adenoma and 385 controls) from two independent Asian groups. Candidate markers were identified by metagenomics and validated by targeted quantitative PCR.ResultsMetagenomic analysis identified ‘m3’ from a Lachnoclostridium sp., Fusobacterium nucleatum (Fn) and Clostridium hathewayi (Ch) to be significantly enriched in adenoma. Faecal m3 and Fn were significantly increased from normal to adenoma to CRC (p
      Keywords: Open access, Gut
      PubDate: 2020-06-06T02:47:05-07:00
      DOI: 10.1136/gutjnl-2019-318532
      Issue No: Vol. 69, No. 7 (2020)
       
  • Mediterranean diet intervention in overweight and obese subjects lowers
           plasma cholesterol and causes changes in the gut microbiome and metabolome
           independently of energy intake
    • Authors: Meslier, V; Laiola, M, Roager, H. M, De Filippis, F, Roume, H, Quinquis, B, Giacco, R, Mennella, I, Ferracane, R, Pons, N, Pasolli, E, Rivellese, A, Dragsted, L. O, Vitaglione, P, Ehrlich, S. D, Ercolini, D.
      Pages: 1258 - 1268
      Abstract: ObjectivesThis study aimed to explore the effects of an isocaloric Mediterranean diet (MD) intervention on metabolic health, gut microbiome and systemic metabolome in subjects with lifestyle risk factors for metabolic disease.DesignEighty-two healthy overweight and obese subjects with a habitually low intake of fruit and vegetables and a sedentary lifestyle participated in a parallel 8-week randomised controlled trial. Forty-three participants consumed an MD tailored to their habitual energy intakes (MedD), and 39 maintained their regular diets (ConD). Dietary adherence, metabolic parameters, gut microbiome and systemic metabolome were monitored over the study period.ResultsIncreased MD adherence in the MedD group successfully reprogrammed subjects’ intake of fibre and animal proteins. Compliance was confirmed by lowered levels of carnitine in plasma and urine. Significant reductions in plasma cholesterol (primary outcome) and faecal bile acids occurred in the MedD compared with the ConD group. Shotgun metagenomics showed gut microbiome changes that reflected individual MD adherence and increase in gene richness in participants who reduced systemic inflammation over the intervention. The MD intervention led to increased levels of the fibre-degrading Faecalibacterium prausnitzii and of genes for microbial carbohydrate degradation linked to butyrate metabolism. The dietary changes in the MedD group led to increased urinary urolithins, faecal bile acid degradation and insulin sensitivity that co-varied with specific microbial taxa.ConclusionSwitching subjects to an MD while maintaining their energy intake reduced their blood cholesterol and caused multiple changes in their microbiome and metabolome that are relevant in future strategies for the improvement of metabolic health.
      Keywords: Open access, Gut
      PubDate: 2020-06-06T02:47:05-07:00
      DOI: 10.1136/gutjnl-2019-320438
      Issue No: Vol. 69, No. 7 (2020)
       
  • STAT3 activation through IL-6/IL-11 in cancer-associated fibroblasts
           
    • Authors: Heichler, C; Scheibe, K, Schmied, A, Geppert, C. I, Schmid, B, Wirtz, S, Thoma, O.-M, Kramer, V, Waldner, M. J, Büttner, C, Farin, H. F, Pesic, M, Knieling, F, Merkel, S, Grüneboom, A, Gunzer, M, Grützmann, R, Rose-John, S, Koralov, S. B, Kollias, G, Vieth, M, Hartmann, A, Greten, F. R, Neurath, M. F, Neufert, C.
      Pages: 1269 - 1282
      Abstract: ObjectiveCancer-associated fibroblasts (CAFs) influence the tumour microenvironment and tumour growth. However, the role of CAFs in colorectal cancer (CRC) development is incompletely understood.DesignWe quantified phosphorylation of STAT3 (pSTAT3) expression in CAFs of human colon cancer tissue using a tissue microarray (TMA) of 375 patients, immunofluorescence staining and digital pathology. To investigate the functional role of CAFs in CRC, we took advantage of two murine models of colorectal neoplasia and advanced imaging technologies. In loss-of-function and gain-of-function experiments, using genetically modified mice with collagen type VI (COLVI)-specific signal transducer and activator of transcription 3 (STAT3) targeting, we evaluated STAT3 signalling in fibroblasts during colorectal tumour development. We performed a comparative gene expression profiling by whole genome RNA-sequencing of fibroblast subpopulations (COLVI+ vs COLVI–) on STAT3 activation (IL-6 vs IL-11).ResultsThe analysis of pSTAT3 expression in CAFs of human TMAs revealed a negative correlation of increased stromal pSTAT3 expression with the survival of colon cancer patients. In the loss-of-function and gain-of-function approach, we found a critical role of STAT3 activation in fibroblasts in driving colorectal tumourigenesis in vivo. With different imaging technologies, we detected an expansion of activated fibroblasts in colorectal neoplasias. Comparative gene expression profiling of fibroblast subpopulations on STAT3 activation revealed the regulation of transcriptional patterns associated with angiogenesis. Finally, the blockade of proangiogenic signalling significantly reduced colorectal tumour growth in mice with constitutive STAT3 activation in COLVI+ fibroblasts.ConclusionAltogether our work demonstrates a critical role of STAT3 activation in CAFs in CRC development.
      Keywords: Gut
      PubDate: 2020-06-06T02:47:05-07:00
      DOI: 10.1136/gutjnl-2019-319200
      Issue No: Vol. 69, No. 7 (2020)
       
  • Genomic and transcriptomic profiling of carcinogenesis in patients with
           familial adenomatous polyposis
    • Authors: Li, J; Wang, R, Zhou, X, Wang, W, Gao, S, Mao, Y, Wu, X, Guo, L, Liu, H, Wen, L, Fu, W, Tang, F.
      Pages: 1283 - 1293
      Abstract: ObjectiveFamilial adenomatous polyposis (FAP) is characterised by the development of hundreds to thousands of adenomas at different evolutionary stages in the colon and rectum that will inevitably progress to adenocarcinomas if left untreated. Here, we investigated the genetic alterations and transcriptomic transitions from precancerous adenoma to carcinoma.DesignWhole-exome sequencing, whole-genome sequencing and single-cell RNA sequencing were performed on matched adjacent normal tissues, multiregionally sampled adenomas at different stages and carcinomas from six patients with FAP and one patient with MUTYH-associated polyposis (n=56 exomes, n=56 genomes and n=8,757 single cells). Genomic alterations (including copy number alterations and somatic mutations), clonal architectures and transcriptome dynamics during adenocarcinoma carcinogenesis were comprehensively investigated.ResultsGenomic evolutionary analysis showed that adjacent lesions from the same patient with FAP can originate from the same cancer-primed cell. In addition, the tricarboxylic acid cycle pathway was strongly repressed in adenomas and was then slightly alleviated in carcinomas. Cells from the ‘normal’ colon epithelium of patients with FAP already showed metabolic reprogramming compared with cells from the normal colon epithelium of patients with sporadic colorectal cancer.ConclusionsThe process described in the previously reported field cancerisation model also occurs in patients with FAP and can contribute to the formation of adjacent lesions in patients with FAP. Reprogramming of carbohydrate metabolism has already occurred at the precancerous adenoma stage. Our study provides an accurate picture of the genomic and transcriptomic landscapes during the initiation and progression of carcinogenesis, especially during the transition from adenoma to carcinoma.
      Keywords: Open access, Gut
      PubDate: 2020-06-06T02:47:05-07:00
      DOI: 10.1136/gutjnl-2019-319438
      Issue No: Vol. 69, No. 7 (2020)
       
  • The epidemiology of hepatitis delta virus infection in Cameroon
    • Authors: Besombes, C; Njouom, R, Paireau, J, Lachenal, G, Texier, G, Tejiokem, M, Cauchemez, S, Pepin, J, Fontanet, A.
      Pages: 1294 - 1300
      Abstract: ObjectiveTo investigate the distribution and risk factors of hepatitis delta virus (HDV) infection in Cameroon.DesignWe tested for hepatitis B virus (HBV) surface antigen (HBsAg) and anti-HDV antibody 14 150 samples collected during a survey whose participants were representative of the Cameroonian adult population. The samples had already been tested for hepatitis C virus and HIV antibodies.ResultsOverall, 1621/14 150 (weighted prevalence=11.9%) participants were HBsAg positive, among whom 224/1621 (10.6%) were anti-HDV positive. In 2011, the estimated numbers of HBsAg positive and HDV seropositives were 1 160 799 and 122 910 in the 15–49 years age group, respectively. There were substantial regional variations in prevalence of chronic HBV infection, but even more so for HDV (from 1% to 54%). In multivariable analysis, HDV seropositivity was independently associated with living with an HDV-seropositive person (OR=8.80; 95% CI: 3.23 to 24.0), being HIV infected (OR=2.82; 95% CI: 1.32 to 6.02) and living in the South (latitude
      Keywords: Gut
      PubDate: 2020-06-06T02:47:05-07:00
      DOI: 10.1136/gutjnl-2019-320027
      Issue No: Vol. 69, No. 7 (2020)
       
  • Comparison of tenofovir and entecavir on the risk of hepatocellular
           carcinoma and mortality in treatment-naìˆve patients with chronic
           hepatitis B in Korea: a large-scale, propensity score analysis
    • Authors: Lee, S. W; Kwon, J. H, Lee, H. L, Yoo, S. H, Nam, H. C, Sung, P. S, Nam, S. W, Bae, S. H, Choi, J. Y, Yoon, S. K, Han, N. I, Jang, J. W.
      Pages: 1301 - 1308
      Abstract: ObjectiveThe use of tenofovir (TDF) and entecavir (ETV) in patients with chronic hepatitis B (CHB) has led to a decrease in the incidence of hepatocellular carcinoma (HCC) and liver-related events. However, whether there is a difference between the two agents in the extent of improving such outcomes has not been clarified thus far. Therefore, we aimed to compare TDF and ETV on the risk of HCC and mortality.DesignA total of 7015 consecutive patients with CHB who were treated with TDF or ETV between February 2007 and January 2018 at the liver units of the Catholic University of Korea were screened for study eligibility and 3022 patients were finally analysed. Study end points were HCC and all-cause mortality or liver transplantation (LT) within 5 years after the initiation of antiviral therapy. Propensity score matching (PSM) and inverse probability of treatment weighting methods were used.ResultsNo difference was observed between TDF and ETV in the incidence rates of HCC in the entire cohort (HR 1.030; 95% CI 0.703 to 1.509, PSM model, p=0.880) and subgroups of patients with chronic hepatitis and cirrhosis. Also, no difference was observed between TDF and ETV in the incidence rates of all-cause mortality or LT in the entire cohort (HR 1.090; 95% CI 0.622 to 1.911, PSM model, p=0.763), and patients with chronic hepatitis and cirrhosis.ConclusionThis study has demonstrated the clinical outcomes in patients with CHB who received TDF or ETV treatment. There was no difference in the intermediate-term risk of HCC and mortality or LT between the two drugs.
      Keywords: Open access, Gut
      PubDate: 2020-06-06T02:47:05-07:00
      DOI: 10.1136/gutjnl-2019-318947
      Issue No: Vol. 69, No. 7 (2020)
       
  • miR-541 potentiates the response of human hepatocellular carcinoma to
           sorafenib treatment by inhibiting autophagy
    • Authors: Xu, W.-P; Liu, J.-P, Feng, J.-F, Zhu, C.-P, Yang, Y, Zhou, W.-P, Ding, J, Huang, C.-K, Cui, Y.-L, Ding, C.-H, Zhang, X, Lu, B, Xie, W.-F.
      Pages: 1309 - 1321
      Abstract: ObjectiveAutophagy participates in the progression of hepatocellular carcinoma (HCC) and the resistance of HCC cells to sorafenib. We investigated the feasibility of sensitising HCC cells to sorafenib by modulating miR-541-initiated microRNA-autophagy axis.DesignGain- and loss-of-function assays were performed to evaluate the effects of miR-541 on the malignant properties and autophagy of human HCC cells. Autophagy was quantified by western blotting of LC3, transmission electron microscopy analyses and confocal microscopy scanning of mRFP-GFP-LC3 reporter construct. Luciferase reporter assays were conducted to confirm the targets of miR-541. HCC xenograft tumours were established to analyse the role of miR-541 in sorafenib-induced lethality.ResultsThe expression of miR-541 was downregulated in human HCC tissues and was associated with malignant clinicopathologic phenotypes, recurrence and survival of patients with HCC. miR-541 inhibited the growth, metastasis and autophagy of HCC cells both in vitro and in vivo. Prediction software and luciferase reporter assays identified autophagy-related gene 2A (ATG2A) and Ras-related protein Rab-1B (RAB1B) as the direct targets of miR-541. Consistent with the effects of the miR-541 mimic, inhibition of ATG2A or RAB1B suppressed the malignant phenotypes and autophagy of HCC cells. Furthermore, siATG2A and siRAB1B partially reversed the enhancement of the malignant properties and autophagy in HCC cells mediated by the miR-541 inhibitor. More interestingly, higher miR-541 expression predicted a better response to sorafenib treatment, and the combination of miR-541 and sorafenib further suppressed the growth of HCC cells in vivo compared with the single treatment.ConclusionsDysregulation of miR-541-ATG2A/RAB1B axis plays a critical role in patients’ responses to sorafenib treatment. Manipulation of this axis might benefit survival of patients with HCC, especially in the context of the highly pursued strategies to eliminate drug resistance.
      Keywords: Gut
      PubDate: 2020-06-06T02:47:05-07:00
      DOI: 10.1136/gutjnl-2019-318830
      Issue No: Vol. 69, No. 7 (2020)
       
  • USP22 promotes hypoxia-induced hepatocellular carcinoma stemness by a
           HIF1{alpha}/USP22 positive feedback loop upon TP53 inactivation
    • Authors: Ling, S; Shan, Q, Zhan, Q, Ye, Q, Liu, P, Xu, S, He, X, Ma, J, Xiang, J, Jiang, G, Wen, X, Feng, Z, Wu, Y, Feng, T, Xu, L, Chen, K, Zhang, X, Wei, R, Zhang, C, Cen, B, Xie, H, Song, P, Liu, J, Zheng, S, Xu, X.
      Pages: 1322 - 1334
      Abstract: ObjectiveWe aimed to elucidate the mutual regulation mechanism of ubiquitin-specific protease 22 (USP22) and hypoxia inducible factor-1α (HIF1α), and the mechanism they promote the stemness of hepatocellular carcinoma (HCC) cells under hypoxic conditions.DesignCell counting, migration, self-renewal ability, chemoresistance and expression of stemness genes were established to detect the stemness of HCC cells. Immunoprecipitation, ubiquitination assay and chromatin immunoprecipitation assay were used to elucidate the mutual regulation mechanism of USP22 and HIF1α. HCC patient samples and The Cancer Genome Atlas data were used to demonstrate the clinical significance. In vivo USP22-targeting experiment was performed in mice bearing HCC.ResultsUSP22 promotes hypoxia-induced HCC stemness and glycolysis by deubiquitinating and stabilising HIF1α. As direct target genes of HIF1α, USP22 and TP53 can be transcriptionally upregulated by HIF1α under hypoxic conditions. In TP53 wild-type HCC cells, HIF1α induced TP53-mediated inhibition of HIF1α-induced USP22 upregulation. In TP53-mutant HCC cells, USP22 and HIF1α formed a positive feedback loop and promote the stemness of HCC. HCC patients with a loss-of-function mutation at TP53 and high USP22 and/or HIF1α expression tend to have a worse prognosis. The USP22-targeting lipopolyplexes caused high tumour inhibition and high sorafenib sensitivity in mice bearing HCC.ConclusionUSP22 promotes hypoxia-induced HCC stemness by a HIF1α/USP22 positive feedback loop on TP53 inactivation. USP22 is a promising target for the HCC therapy.
      Keywords: Gut
      PubDate: 2020-06-06T02:47:05-07:00
      DOI: 10.1136/gutjnl-2019-319616
      Issue No: Vol. 69, No. 7 (2020)
       
  • COVID-19 and immunomodulation in IBD
    • Authors: Neurath; M. F.
      Pages: 1335 - 1342
      Abstract: The current coronavirus pandemic is an ongoing global health crisis due to COVID-19, caused by severe acute respiratory syndrome coronavirus 2. Although COVID-19 leads to little or mild flu-like symptoms in the majority of affected patients, the disease may cause severe, frequently lethal complications such as progressive pneumonia, acute respiratory distress syndrome and organ failure driven by hyperinflammation and a cytokine storm syndrome. This situation causes various major challenges for gastroenterology. In the context of IBD, several key questions arise. For instance, it is an important question to understand whether patients with IBD (eg, due to intestinal ACE2 expression) might be particularly susceptible to COVID-19 and the cytokine release syndrome associated with lung injury and fatal outcomes. Another highly relevant question is how to deal with immunosuppression and immunomodulation during the current pandemic in patients with IBD and whether immunosuppression affects the progress of COVID-19. Here, the current understanding of the pathophysiology of COVID-19 is reviewed with special reference to immune cell activation. Moreover, the potential implications of these new insights for immunomodulation and biological therapy in IBD are discussed.
      Keywords: GUT Recent advances in basic science, Open access, Gut, COVID-19
      PubDate: 2020-06-06T02:47:05-07:00
      DOI: 10.1136/gutjnl-2020-321269
      Issue No: Vol. 69, No. 7 (2020)
       
  • Advances in non-invasive assessment of hepatic fibrosis
    • Authors: Loomba, R; Adams, L. A.
      Pages: 1343 - 1352
      Abstract: Liver fibrosis should be assessed in all individuals with chronic liver disease as it predicts the risk of future liver-related morbidity and thus need for treatment, monitoring and surveillance. Non-invasive fibrosis tests (NITs) overcome many limitations of liver biopsy and are now routinely incorporated into specialist clinical practice. Simple serum-based tests (eg, Fibrosis Score 4, non-alcoholic fatty liver disease Fibrosis Score) consist of readily available biochemical surrogates and clinical risk factors for liver fibrosis (eg, age and sex). These have been extensively validated across a spectrum of chronic liver diseases, however, tend to be less accurate than more ‘complex’ serum tests, which incorporate direct measures of fibrogenesis or fibrolysis (eg, hyaluronic acid, N-terminal propeptide of type three collagen). Elastography methods quantify liver stiffness as a marker of fibrosis and are more accurate than simple serum NITs, however, suffer increasing rates of unreliability with increasing obesity. MR elastography appears more accurate than sonographic elastography and is not significantly impacted by obesity but is costly with limited availability. NITs are valuable for excluding advanced fibrosis or cirrhosis, however, are not sufficiently predictive when used in isolation. Combining serum and elastography techniques increases diagnostic accuracy and can be used as screening and confirmatory tests, respectively. Unfortunately, NITs have not yet been demonstrated to accurately reflect fibrosis change in response to treatment, limiting their role in disease monitoring. However, recent studies have demonstrated lipidomic, proteomic and gut microbiome profiles as well as microRNA signatures to be promising techniques for fibrosis assessment in the future.
      Keywords: GUT Recent advances in clinical practice, Gut
      PubDate: 2020-06-06T02:47:05-07:00
      DOI: 10.1136/gutjnl-2018-317593
      Issue No: Vol. 69, No. 7 (2020)
       
  • GI highlights from the literature
    • Authors: Smith; P. J.
      Pages: 1353 - 1354
      Abstract: Basic scienceDistinct microbial and immune niches of the human colon James K, Gomes T, Elmentaite R. et al. Distinct microbial and immune niches of the human colon. Nat Immunol 2020;21:343–53. Simultaneous analyses of gut microbes and neighbouring immune cells are essential to understand the significance of environmental signals and their role in shaping the gut environment. Understanding what constitutes a healthy relationship between these compartments is of critical importance if we are to elucidate their involvement in both health and disease. The GI microbiota composition is highly regulated by the local environment including nutrient and oxygen levels. Alongside this, there is evidence of regional variation in immune cells. However, understanding to what extent regional microbial signatures influences local immune cell numbers/function has not been investigated. James et al catalogued colonic mucosal microbial signatures in parallel with single-cell RNA sequencing to document steady-state immune cell populations in colonic...
      Keywords: Gut
      PubDate: 2020-06-06T02:47:05-07:00
      DOI: 10.1136/gutjnl-2020-321714
      Issue No: Vol. 69, No. 7 (2020)
       
  • Tracing the accumulation of in vivo human oral microbiota elucidates
           microbial community dynamics at the gateway to the GI tract
    • Authors: Wang, J; Jia, Z, Zhang, B, Peng, L, Zhao, F.
      Pages: 1355 - 1356
      Abstract: With great interest we read the article by Gaiser et al1 that enrichment of oral bacterial taxa in pancreatic cancer highlights the role of oral microbiota. Not coincidentally, the presence of Fusobacterium nucleatum in paired saliva and colon samples of the patients with colorectal cancer has been reported,2 3 raising interest in whether disease starts in the mouth or in the intestine.4–6 Another reason people are interested in oral microbes is their potentials serving as biomarkers for systemic diseases.3 7–9 In this study, we examined how long the collapsed bacterial community can recover to its initial state when suffering from disturbance and whether oral microbes have sufficient robustness to serve as biomarkers. We longitudinally tracked the re-assembling process of human oral biofilms after clinical scaling. Paired saliva and dental...
      Keywords: Open access, Gut
      PubDate: 2020-06-06T02:47:05-07:00
      DOI: 10.1136/gutjnl-2019-318977
      Issue No: Vol. 69, No. 7 (2020)
       
  • Giant oversights in the human gut virome
    • Authors: Sutton, T. D. S; Clooney, A. G, Hill, C.
      Pages: 1357 - 1358
      Abstract: We read with interest the paper by Zuo et al,1 which used deep sequencing to identify gut mucosal virome alterations in individuals with UC. One of many interesting findings reported by the authors was the detection of giant viruses infecting algae and amoeba (Mimivirus and Chrysochromulina ericina virus). The authors suggested an association with the geographical distribution of individuals and concluded that they were more abundant in patients with UC than controls. We reanalysed the data and propose that issues related to the virome analysis pipeline led to the incorrect identification of these viruses. First, the DNA extraction method states that 0.22 µm filters were used to remove bacterial and eukaryotic cells, followed by chemical and enzymatic degradation of DNA unprotected by viral capsids. Mimivirus has a capsid with a diameter of 0.5 µm, surrounded by a 0.125 µm thick layer of closely packed fibres,2 making its presence in the final...
      Keywords: Gut
      PubDate: 2020-06-06T02:47:05-07:00
      DOI: 10.1136/gutjnl-2019-319067
      Issue No: Vol. 69, No. 7 (2020)
       
  • Towards standardisation of naming novel prokaryotic taxa in the age of
           high-throughput microbiology
    • Authors: Hildebrand, F; Pallen, M. J, Bork, P.
      Pages: 1358 - 1359
      Abstract: We thank Professor Oren for his interest in our work and for his constructive comments.1 In our recent article in Gut, we described the discovery of a new species that rose to high abundance in the human gut after treatment with ceftriaxone.2 We made the decision to propose taxonomic Latin names for this new species and for associated taxa because we wished to create a memorable, user-friendly, sustainable and transferable nomenclature that could be readily adopted by other researchers. Our proposals included the taxonomic hierarchy: UComantemales ord. nov., UComantemaea fam. nov., UBorkfalki gen. nov, UBorkfalki ceftriaxensis sp. nov. We adopted the superscript ‘U’ (for ‘uncultured’) prefix in line with a recent suggestion3 but accept that use of Candidatus has priority. However, in our defence, it is worth noting that recommendations for use of Candidatus cited by Professor Oren state that ‘this category should...
      Keywords: Open access, Gut
      PubDate: 2020-06-06T02:47:05-07:00
      DOI: 10.1136/gutjnl-2019-319045
      Issue No: Vol. 69, No. 7 (2020)
       
  • Authors response: giant oversights in the human gut virome
    • Authors: Zuo, T; Ng, S. C.
      Pages: 1358 - 1358
      Abstract: We explored gut mucosal virome alterations in UC1 and appreciate the insightful comments from the authors who highlighted some of the important limitations of human gut virome studies.2 Unlike the bacteria microbiome, the gut virome remains largely underexplored. There is currently no gold standard on the optimal pipelines or methods for virome analysis. In addition, the lack of consensus in both methodology and virus taxonomy classification underscores significant limitations and challenges in virome metagenomics analysis.3 4 Most metagenomic studies of the human gut virome have adopted practical methods based on filtration with subsequent precipitation or ultrafiltration of virus-like particles (VLPs).3 Such protocols including that of ours can introduce considerable amounts of residual DNA into the samples, such as DNA from human and bacteria, due to insufficient filtration and purification,3 which may result in concomitant presence of residual...
      Keywords: Gut
      PubDate: 2020-06-06T02:47:05-07:00
      DOI: 10.1136/gutjnl-2019-319357
      Issue No: Vol. 69, No. 7 (2020)
       
  • {beta}6 integrinosis: a new lethal autosomal recessive ITGB6 disorder
           leading to impaired conformational transitions of the {alpha}V{beta}6
           integrin receptor
    • Authors: Weil, P; van den Bruck, R, Ziegenhals, T, Juranek, S, Goedde, D, Orth, V, Wirth, S, Jenke, A. C, Postberg, J.
      Pages: 1359 - 1361
      Abstract: We read with interest the recent work by Schleier et al1 demonstrating consequences of impaired α4β7 integrin-dependent gut homing of intestinal macrophages on wound healing, which fits well with own observations we have made in a case of congenital infantile intractable diarrhoea linked to impaired integrin receptors in intestinal epithelia (αVβ6). Specifically, a male dizygotic twin was delivered dystrophic (1715 g) at 36 weeks of gestational age and developed intractable diarrhoea within the following 2 months, contrary to his twin brother. Severe systemic infection or parasitosis was ruled out, but subsequently low-serum IgG and severe neutropenia occurred due to consumption of neutrophils during the prolonged diarrhoea. Eventually, he developed cholestatic hepatopathy and thrombocytopenia and died of uncontrollable GI, dermal haemorrhages and hepatic failure at 7 months of age. Extensive diagnostics included biopsies of liver, muscle, bone marrow, small intestine, the exclusion of known congenital diarrhoea reasons and immunodeficiencies by...
      Keywords: Open access, Gut
      PubDate: 2020-06-06T02:47:05-07:00
      DOI: 10.1136/gutjnl-2019-319015
      Issue No: Vol. 69, No. 7 (2020)
       
  • Trust is good, control is better: technical considerations in blood
           microbiome analysis
    • Authors: Schierwagen, R; Alvarez-Silva, C, Servant, F, Trebicka, J, Lelouvier, B, Arumugam, M.
      Pages: 1362 - 1363
      Abstract: We agree with Hornung et al1 that studying blood microbiome is a major technical challenge with potential artefacts. At least three important challenges must be tackled:
      Low amount of bacterial DNA in blood.2
      High amounts of PCR inhibitors.
      Bacterial DNA contaminants from environment, reagents and consumables. Measuring, reducing and controlling bacterial contaminants are key elements of optimisations made on the molecular pipeline used in our study3 as well as eight published studies on blood microbiome.2 4–7 The studies from Salter et al8 and Laurence et al9 are useful to understand the burden of bacterial contaminants when working with low bacterial abundance samples. In former publications,2 10 we have described our procedure and the controls performed to address such contamination. One must be...
      Keywords: Open access, Gut
      PubDate: 2020-06-06T02:47:05-07:00
      DOI: 10.1136/gutjnl-2019-319123
      Issue No: Vol. 69, No. 7 (2020)
       
  • Absence of hepatitis E virus RNA in semen samples of infertile male in
           China
    • Authors: Wang, L; Zhang, Z, Shu, J, Zhang, H, Yang, Y, Liang, Z, He, Q, Huang, W, Wang, Y, Zhuang, H, Jiang, H, Wang, L.
      Pages: 1363 - 1364
      Abstract: Hepatitis E virus (HEV) RNA has been recently discovered in semen samples of Chinese infertile man with a remarkably high rate of 28.1% (52/185, table 1).1 All HEV isolates belong to HEV genotype 4 (HEV4), which is the dominant strain prevalent in China. This intriguing discovery has aroused our attention. In a recent response to the work done by Huang et al, researchers in Germany tested 87 semen samples collected from infertile men, but the HEV RNA positive rate is 0% (table 1).2 Germany is prevalent with HEV3, so the authors suggested that HEV genotype-specific or variant-specific pathophysiology may explain the contrary results. However, the two studies both have limitations to reach a more accurate conclusion. The size of patients included in both studies is relatively small, and the nature of the patient cohorts is mainly retrospective. Moreover, it is important...
      Keywords: Gut
      PubDate: 2020-06-06T02:47:05-07:00
      DOI: 10.1136/gutjnl-2019-319234
      Issue No: Vol. 69, No. 7 (2020)
       
  • COVID-19 infection in Crohns disease under treatment with adalimumab
    • Authors: Tursi, A; Angarano, G, Monno, L, Saracino, A, Signorile, F, Ricciardi, A, Papa, A.
      Pages: 1364 - 1365
      Abstract: Jin et al described recently 74 cases of people having COVID-19 and experiencing gastrointestinal symptoms.1 In Italy, we are managing a dramatically increasing number of people infected with severe acute respiratory syndrome corona virus 2, the virus causing COVID-19.2 3 Despite the Italian Government has implemented extraordinary measures to restrict viral spread, including significant decrease of air and train traffic within the country, cases are increasing (>75 000 people until 26 March 2020) also in other regions than Lombardy, which is the main Italian region affected from COVID-19 (>35 000 people until 26 March 2020).4 This means that a lot of people under immunosuppressive-immunomodulating therapies could be infected by this virus, and that the immunosuppressive status could influence both the status of the basic disease and both the course of pulmonary disease. A 30-year-old male was admitted on emergency department of...
      Keywords: Gut, COVID-19
      PubDate: 2020-06-06T02:47:05-07:00
      DOI: 10.1136/gutjnl-2020-321240
      Issue No: Vol. 69, No. 7 (2020)
       
  • Severe liver failure during SARS-CoV-2 infection
    • Authors: Weber, S; Mayerle, J, Irlbeck, M, Gerbes, A. L.
      Pages: 1365 - 1367
      Abstract: We read with interest the recently described affections of the GI system in coronavirus disease (COVID-19).1 2 In addition to the effects on the gut, mild abnormalities in liver aminotransferase levels have been observed.3 4 We here report a previously non-described severe liver failure in a patient with COVID-19. A 65-year-old man was admitted to our emergency department with fever up to 40°C, dry cough and dyspnoea. The chest CT scan showed typical features of COVID-19, such as ground-glass opacities and peripheral consolidations. A throat swab confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Aminotransferase concentrations were slightly increased (alanine aminotransferase (ALT) 69 U/L and aspartate aminotransferase (AST) 92 U/L; upper limit of normal (ULN) ≤49 U/L). He had been receiving long-term treatment with hydrochlorothiazide and ramipril for arterial hypertension as sole medications and had no history of liver disease. The patient was...
      Keywords: Gut, COVID-19
      PubDate: 2020-06-06T02:47:05-07:00
      DOI: 10.1136/gutjnl-2020-321350
      Issue No: Vol. 69, No. 7 (2020)
       
  • APSDE-COVID statements: recommendations should be modified according to
           the prevalence of COVID infection rates
    • Authors: Bhandari, P; Alkandari, A.
      Pages: 1367 - 1368
      Abstract: We read the article from Chiu et al1 and would like to congratulate the authors and Asian Pacific Society for producing APSDE (Asian-Pacific Society for Digestive Endoscopy)-COVID statements. The statements make perfect practical sense in the times where robust evidence is lacking. However, there are some conflicting messages coming out and I would like to draw attention toward it. Figure 1 is suggesting a very extensive algorithm of clinical and laboratory testing to identify the infective potential of the patient and based on that to decide if urgent or semiurgent or elective endoscopy should be performed and the type of personal protective equipment (PPE) to be used. However, statement 2 clearly indicates and quiet rightly so that in the current pandemic we should only perform endoscopy for urgent indications. I feel that the algorithm in figure 1 is best suited for countries with low incidence or recovering...
      Keywords: Gut, COVID-19
      PubDate: 2020-06-06T02:47:05-07:00
      DOI: 10.1136/gutjnl-2020-321360
      Issue No: Vol. 69, No. 7 (2020)
       
 
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