For some time it has been recognised that alterations in the gut bacteria are associated with Inflammatory Bowel Disease. However, it is unclear which is the chicken and which is the egg – does this “dysbiosis” arise due to genetic differences in affected individuals or because of the inflammatory conditions present in the intestine, or is it causative and a prerequisite for disease to develop, and if so how?

Low bone mineral density (BMD) is both prevalent and frequently unrecognised in patients with inflammatory bowel disease (IBD). With osteoporosis occurring at a rate of 10–14% in the IBD population already at a median age of 33–41 years, low BMD can well be considered an extra intestinal manifestation of IBD. Despite this, and the availability of guidelines from the American Gastroenterological Association and the American College of Gastroenterology, testing rates for osteoporosis have been reported to be low in IBD patients [1, 2].

Introduction: The IL-12 family of cytokines plays an important role in the pathogenesis of IBD. It consists of pro-inflammatory cytokines enhancing inflammation by induction of Th1/ Th17 responses, like IL-12 and IL-23, but also of members with an immunosuppressive function, like IL-27 and IL-35.
Interestingly, the IL-12 family consists of heterodimeric cytokines composed of two subunits, some of which are shared amongst family members. IL-27 is composed of EBI3 (Epstein-Barr virus-induced gene 3) and the IL-27p28 subunit, whereas IL-35 is composed of EBI3 and IL-12p35. In contrast to the well-defined function of IL-12 and IL-23 in IBD, the function of IL-27 and IL-35 is still unclear. In particular, functional studies of IL-35 are hampered by the current limitations in our ability to detect it and the fact that knockout of the EBI3 subunit will also affect IL-27 expression and knock-out of the IL-12p35 unit will also affect IL-12 expression.
Wirtz et al. elegantly circumvented this problem by using mice deficient in both EBI3 (lacking both IL-27 and IL-35) and IL-27p28 (lacking only IL-27) to gain insight into the role of IL-35. The differences between the EBI3 and IL-27p28 deficiency were studied in a variety of established mouse colitis models, using state of the art imaging tools, i.e. murine endoscopy and bioluminescence, to assess colonic inflammation in vivo.

Introduction:Infliximab (IFX) has dramatically changed the approach to the management of patients with Crohn’s Disease (CD) [1]. IFX induces rapid and profound endoscopic healing, improves quality of life and allows patients to avoid hospitalisation and surgery [2]. The ACCENT I [3] and ACCENT II [4] trials have shown that scheduled maintenance therapy with IFX is superior to episodic therapy in maintaining response and remission both in luminal and in fistulising CD. Nonetheless, approximately 60% of patients cannot reach remission and 25–40% of patients on an IFX maintenance regimen experience a loss of response to the drug [5].
It has been demonstrated that the combination of IFX and azathioprine is more effective than IFX alone in inducing steroid-free remission and mucosal healing of the bowel in luminal CD in patients not treated previously with azathioprine. The Study of Biologic and Immunomodulator Naive Patients in Crohn’s Disease (SONIC) also showed that IFX monotherapy is significantly better at inducing steroid-free remission and mucosal healing than azathioprine alone in azathioprine-naive patients [6].
It is important, however, to determine whether IFX therapy can be safely interrupted in patients with CD who have undergone a period of prolonged remission, and the timing of IFX withdrawal in patients who receive combination therapy is one of the most controversial topics in IBD management.

Colorectal cancer (CRC) and small bowel adenocarcinoma (SBA) are severe com-plications of inflammatory bowel dis-eases (IBD) and represent a major concern in the follow-up of these patients. The association between CRC and ulcerative colitis has been well established since the first case was described in 1925, whereas conflicting data about the risk of CRC in Crohn’s disease (CD) have been reported in the literature. A strong association between CD and small bowel cancer has been established without any reduction of this risk in recent decades. The risk of CRC in CD is less clear. An increase in risk of about 2.5-fold has been reported in several studies, including two recent meta-analyses, whereas other studies reported no increased risk of CRC in the CD population. The well-established risk factors for CRC in IBD are disease duration, an early age at diagnosis (usually associated with long disease duration), the disease location (colonic loca-tion and extensive disease), a familial history of CRC, concomitant primary sclerosing cholangitis and male gender. Environmental, dietary and genetic factors can influence the risk of CRC and small bowel adenocarcinoma. Geo-graphic variations have been reported, with an increased risk in North America and the United Kingdom.

The first ECCO pathogenesis workshop focused on anti-TNF therapy failures in inflammatory bowel diseases (IBDs). The overall objective was to better understand and explore primary non response and loss of response to anti-TNF agents in IBD. The outcome of this workshop is presented into two parts. This first section addresses definitions, frequency and pharmacological aspects of anti-TNF therapy failure, including pharmacokinetics of anti-TNF monoclonal antibodies and immune and non-immune mediated clearance of anti-TNF mAbs. The second section concerns the biological roles of TNF and TNF antagonists, including mechanisms of action of anti-TNF agents, and discuss hypothesis regarding their failures and phenomenon of paradoxical inflammation, including the potential role of TNF independent inflammatory pathways.

This second section of the first ECCO pathogenesis workshop on anti-TNF therapy failures in inflammatory bowel diseases addresses the biological roles of TNFα and the effects and mechanisms of action of TNFα antagonists. Mechanisms underlying their failure, including induction of TNF-independent inflammatory pathways and phenomena of paradoxical inflammation are discussed.

Understanding the biological activity of tumor-necrosis factor alpha (TNFα) and its available antagonists is essential in order to delineate mechanisms for anti-TNF failures. In this section, we review and discuss the current knowledge regarding possible mechanisms leading to failures of anti-TNF antibodies in the context of their effects at the cellular level, TNF-receptor mediated activities, transmembrane TNF-mediated activities, and the effect of TNFα and anti-TNF agents on different cell types and tissues.

Clinically effective therapies now exist for remission maintenance in both ulcerative colitis [UC] and Crohn’s Disease [CD]. For each major class of IBD medications [5-aminosalicyclates, immunomodulators, and biologic agents], used alone or in combination, there is a risk of relapse following reduction or cessation of treatment. A consensus expert panel convened by the European Crohn’s and Colitis Organisation [ECCO] reviewed the published literature and agreed a series of consensus practice points. The objective of the expert consensus is to provide evidence-based guidance for clinical practice so that physicians can make informed decisions in partnership with their patients. The likelihood of relapse with stopping each class of IBD medication is reviewed. Factors associated with an altered risk of relapse with withdrawal are evaluated, and strategies to monitor and allow early identification of relapse are considered. In general, patients in clinical, biochemical, and endoscopic remission are more likely to remain well when treatments are stopped. Reintroduction of the same treatment is usually, but not always, successful. The decision to stop a treatment needs to be individualized, and shared decision making with the patient should take place.