http://gut.bmj.com This feed contains articles for Gut Subject Collection "Gut Education" Gut http://gut.bmj.com http://gut.bmj.com/cgi/content/short/62/6/920?rss=1 Introduction The 10th anniversary of the publication of the first draft sequence of the human genome was celebrated recently, following the launch of the Human Genome Project in 1990.1 Now, 10 years later, a human genome can be sequenced in less than 10 days and soon will be sequenced routinely within a day. This remarkable progress is due to significant advances in DNA sequencing technologies from Sanger sequencing that has been dominant for nearly 30 years to next generation sequencing (NGS, also termed massively parallel sequencing). The ability to rapidly sequence human genomes and to generate genetic, transcriptomic, epigenetic data and other genome-wide data for a relatively small cost opens up numerous opportunities for translation into the clinic over the next few years. Can the knowledge gained through NGS advances lead to personalized medicine for cancer patients? In this review we provide an overview of NGS technologies and the challe ... Casey, G. Conti, D. Haile, R. Duggan, D. 2013-06-01 doi:10.1136/gutjnl-2011-301935 Next generation sequencing and a new era of medicine British Society of Gastroenterology 6 62 932 920 2013-06-01 RECENT ADVANCES IN BASIC SCIENCE http://gut.bmj.com/cgi/content/short/62/4/616?rss=1 Throughout the human gastrointestinal tract a variety of reactive nitrogen oxides are continuously formed as a result of a complex interplay between the host, commensal bacteria and dietary factors. These compounds include nitric oxide, nitrite, nitrate, peroxynitrite, S-nitrosothiols, nitrated fatty acids and N-nitrosamines, all of which are bioactive with the potential to affect physiological and pathological processes locally in the gut as well as systemically after absorption. Historically, the literature has been dominated by studies on the formation of potentially carcinogenic nitrosamines, but the focus was shifted in the 1980s with the seminal discovery of the L-arginine-nitric oxide pathway and its profound impact on normal physiological functions. More recently, a nitrate-nitrite-nitric oxide pathway has been discovered, with implications for local host defence and gut mucosal integrity and, intriguingly, also for systemic regulation of cardiovascular and metabolic function. This review discusses recent advances in the understanding of the formation, biochemistry, physiology and pathophysiology of reactive nitrogen oxides in the gastrointestinal tract. In addition, opportunities for nitric oxide-based pharmacological or dietary interventions are highlighted. Lundberg, J. O. Weitzberg, E. 2013-04-01 doi:10.1136/gutjnl-2011-301649 Biology of nitrogen oxides in the gastrointestinal tract British Society of Gastroenterology 4 62 629 616 2013-04-01 RECENT ADVANCES IN BASIC SCIENCE http://gut.bmj.com/cgi/content/short/62/1/146?rss=1 Advances in sequencing technology and the development of metagenomic and bioinformatics methods have opened up new ways to investigate the 1014 microorganisms inhabiting the human gut. The gene composition of human gut microbiome in a large and deeply sequenced cohort highlighted an overall non-redundant genome size 150 times larger than the human genome. The in silico predictions based on metagenomic sequencing are now actively followed, compared and challenged using additional omics' technologies. Interactions between the microbiota and its host are of key interest in several pathologies and applying meta-omics to describe the human gut microbiome will give a better understanding of this crucial crosstalk at mucosal interfaces. Adding to the growing appreciation of the importance of the microbiome is the discovery that numerous phages, that is, viruses of prokaryotes infecting bacteria (bacteriophages) or archaea with a high host specificity, inhabit the human gut and impact microbial activity. In addition, gene exchanges within the gut microbiota have proved to be more frequent than anticipated. Taken together, these innovative exploratory technologies are expected to unravel new information networks critical for gut homeostasis and human health. Among the challenges faced, the in vivo validation of these networks, together with their integration into the prediction and prognosis of disease, may require further working hypothesis and collaborative efforts. Lepage, P. Leclerc, M. C. Joossens, M. Mondot, S. Blottiere, H. M. Raes, J. Ehrlich, D. Dore, J. 2013-01-01 doi:10.1136/gutjnl-2011-301805 A metagenomic insight into our gut's microbiome British Society of Gastroenterology 1 62 158 146 2013-01-01 RECENT ADVANCES IN BASIC SCIENCE http://gut.bmj.com/cgi/content/short/62/1/159?rss=1 It is increasingly perceived that gut host-microbial interactions are important elements in the pathogenesis of functional gastrointestinal disorders (FGID). The most convincing evidence to date is the finding that functional dyspepsia and irritable bowel syndrome (IBS) may develop in predisposed individuals following a bout of infectious gastroenteritis. There has been a great deal of interest in the potential clinical and therapeutic implications of small intestinal bacterial overgrowth in IBS. However, this theory has generated much debate because the evidence is largely based on breath tests which have not been validated. The introduction of culture-independent molecular techniques provides a major advancement in our understanding of the microbial community in FGID. Results from 16S rRNA-based microbiota profiling approaches demonstrate both quantitative and qualitative changes of mucosal and faecal gut microbiota, particularly in IBS. Investigators are also starting to measure host-microbial interactions in IBS. The current working hypothesis is that abnormal microbiota activate mucosal innate immune responses which increase epithelial permeability, activate nociceptive sensory pathways and dysregulate the enteric nervous system. While we await important insights in this field, the microbiota is already a therapeutic target. Existing controlled trials of dietary manipulation, prebiotics, probiotics, synbiotics and non-absorbable antibiotics are promising, although most are limited by suboptimal design and small sample size. In this article, the authors provide a critical review of current hypotheses regarding the pathogenetic involvement of microbiota in FGID and evaluate the results of microbiota-directed interventions. The authors also provide clinical guidance on modulation of gut microbiota in IBS. Simren, M. Barbara, G. Flint, H. J. Spiegel, B. M. R. Spiller, R. C. Vanner, S. Verdu, E. F. Whorwell, P. J. Zoetendal, E. G. 2013-01-01 doi:10.1136/gutjnl-2012-302167 Intestinal microbiota in functional bowel disorders: a Rome foundation report British Society of Gastroenterology 1 62 176 159 2013-01-01 RECENT ADVANCES IN CLINICAL PRACTICE http://gut.bmj.com/cgi/content/short/61/9/1340?rss=1 Approximately a third of patients with suspected gastro-oesophageal reflux disease are resistant or partial responders to proton pump inhibitors (PPIs). Many of these patients do not have gastro-oesophageal reflux disease, but suffer from functional heartburn or dyspepsia. The potential mechanisms underlying failure of PPI treatment in patients with reflux-related symptoms include persistence of isolated or mixed acid, weakly acidic, bile or gas reflux, impaired oesophageal mucosal integrity, chemical or mechanical hypersensitivity to refluxates and psychological comorbidity. After thorough clinical evaluation and failure of empirical changes in PPI dose regime, diagnostic investigations include endoscopy and reflux monitoring with pH or pH-impedance monitoring. If symptoms are clearly related to persistent reflux, baclofen, antireflux surgery or pain modulators can be considered. If not, pain modulators are the only currently available therapy. Sifrim, D. Zerbib, F. 2012-09-01 doi:10.1136/gutjnl-2011-301897 Diagnosis and management of patients with reflux symptoms refractory to proton pump inhibitors British Society of Gastroenterology 9 61 1354 1340 2012-09-01 RECENT ADVANCES IN CLINICAL PRACTICE http://gut.bmj.com/cgi/content/short/61/9/1355?rss=1 Coeliac disease is a gut disease driven by an abnormal immune response towards dietary gluten in genetically susceptible individuals. Whether and, if so, how abnormal transport of gluten across the gut epithelium may participate in the pathogenesis of coeliac disease remains debatable. This paper summarises the interactions of gluten-derived peptides with the intestinal epithelium and discusses the mechanisms that control their transport across the epithelium. It shows how recent data point to a key role for the transcellular pathway and highlights the Trojan horse' role of secretory IgA which can hijack the transferrin receptor and allow the rapid translocation of intact gluten peptides into the mucosa. These recent findings might be useful for the design of new treatments. Heyman, M. Abed, J. Lebreton, C. Cerf-Bensussan, N. 2012-09-01 doi:10.1136/gutjnl-2011-300327 Intestinal permeability in coeliac disease: insight into mechanisms and relevance to pathogenesis British Society of Gastroenterology 9 61 1364 1355 2012-09-01 RECENT ADVANCES IN BASIC SCIENCE http://gut.bmj.com/cgi/content/short/61/8/1219?rss=1 Introduction Bacterial infections continue to be a leading cause of mortality andacute-on-chronic liver failure in end-stage liver disease (ESLD). The consequences of infection include prolonged hospitalisation, acute kidney injury (AKI), death, de-listing from liver transplant and susceptibility to further infections. The diagnosis of infections in cirrhosis is fraught due to the background of a partial systemic inflammatory response syndrome (SIRS) state and negative cultures in 30-50% of patients. Furthermore, the lack of multi-center studies limits the generalisability of currently available results. The modulation of infections by the underlying immune state, gut barrier function and super-imposed medications such as beta-blockers, proton pump inhibitors and antibiotics is required. A rational approach to the diagnosis and prevention of AKI associated with infection, withjudicious use of crystalloids and albumin, is also needed. Changes in bacteriology including emergence of mult ... Bajaj, J. S. O'Leary, J. G. Wong, F. Reddy, K. R. Kamath, P. S. 2012-08-01 doi:10.1136/gutjnl-2012-302339 Bacterial infections in end-stage liver disease: current challenges and future directions British Society of Gastroenterology 8 61 1225 1219 2012-08-01 RECENT ADVANCES IN CLINICAL PRACTICE http://gut.bmj.com/cgi/content/short/61/8/1226?rss=1 Over recent years, it has become increasingly accepted that virus-specific CD4+ and CD8+ T cell responses play a major role in outcome and pathogenesis of hepatitis C virus (HCV) infection. Indeed, while the emergence of strong and multispecific T cell responses may correlate with spontaneous viral clearance, the virus has developed several mechanisms to avoid T cell control in the majority of acutely HCV-infected patients that subsequently develop persistent HCV infection. In this review, we will discuss the current knowledge about the role of cellular immune responses in HCV infection. Specifically, we will emphasise recent new insights into the effector functions of T cells, possible mechanisms of their failure and the host-virus interactions occurring at the site of the disease, the liver. Klenerman, P. Thimme, R. 2012-08-01 doi:10.1136/gutjnl-2011-300620 T cell responses in hepatitis C: the good, the bad and the unconventional British Society of Gastroenterology 8 61 1234 1226 2012-08-01 RECENT ADVANCES IN BASIC SCIENCE http://gut.bmj.com/cgi/content/short/gutjnl-2012-302830v1?rss=1 Recent studies have identified mucosal healing on endoscopy as a key prognostic parameter in the management of inflammatory bowel diseases (IBD), thus highlighting the role of endoscopy for monitoring of disease activity in IBD. In fact, mucosal healing has emerged as a key treatment goal in IBD that predicts sustained clinical remission and resection-free survival of patients. The structural basis of mucosal healing is an intact barrier function of the gut epithelium that prevents translocation of commensal bacteria into the mucosa and submucosa with subsequent immune cell activation. Thus, mucosal healing should be considered as an initial event in the suppression of inflammation of deeper layers of the bowel wall, rather than as a sign of complete healing of gut inflammation. In this systematic review, the clinical studies on mucosal healing are summarised and the effects of anti-inflammatory or immunosuppressive drugs such as 5-aminosalicylates, corticosteroids, azathioprine, ciclosporin and anti-TNF antibodies (adalimumab, certolizumab pegol, infliximab) on mucosal healing are discussed. Finally, the implications of mucosal healing for subsequent clinical management in patients with IBD are highlighted. Neurath, M. F. Travis, S. P. L. 2012-07-27 doi:10.1136/gutjnl-2012-302830 Mucosal healing in inflammatory bowel diseases: a systematic review British Society of Gastroenterology 2012-07-27 RECENT ADVANCES IN CLINICAL PRACTICE http://gut.bmj.com/cgi/content/short/gutjnl-2012-302167v2?rss=1 It is increasingly perceived that gut host-microbial interactions are important elements in the pathogenesis of functional gastrointestinal disorders (FGID). The most convincing evidence to date is the finding that functional dyspepsia and irritable bowel syndrome (IBS) may develop in predisposed individuals following a bout of infectious gastroenteritis. There has been a great deal of interest in the potential clinical and therapeutic implications of small intestinal bacterial overgrowth in IBS. However, this theory has generated much debate because the evidence is largely based on breath tests which have not been validated. The introduction of culture-independent molecular techniques provides a major advancement in our understanding of the microbial community in FGID. Results from 16S rRNA-based microbiota profiling approaches demonstrate both quantitative and qualitative changes of mucosal and faecal gut microbiota, particularly in IBS. Investigators are also starting to measure host-microbial interactions in IBS. The current working hypothesis is that abnormal microbiota activate mucosal innate immune responses which increase epithelial permeability, activate nociceptive sensory pathways and dysregulate the enteric nervous system. While we await important insights in this field, the microbiota is already a therapeutic target. Existing controlled trials of dietary manipulation, prebiotics, probiotics, synbiotics and non-absorbable antibiotics are promising, although most are limited by suboptimal design and small sample size. In this article, the authors provide a critical review of current hypotheses regarding the pathogenetic involvement of microbiota in FGID and evaluate the results of microbiota-directed interventions. The authors also provide clinical guidance on modulation of gut microbiota in IBS. Simren, M. Barbara, G. Flint, H. J. Spiegel, B. M. R. Spiller, R. C. Vanner, S. Verdu, E. F. Whorwell, P. J. Zoetendal, E. G. 2012-07-10 doi:10.1136/gutjnl-2012-302167 Intestinal microbiota in functional bowel disorders: a Rome foundation report British Society of Gastroenterology 2012-07-10 RECENT ADVANCES IN CLINICAL PRACTICE