Dr Christen Rune Stensvold is a Senior Scientist and Public Health Microbiologist with specialty in parasitology. He has a Bachelor degree in Medical Sciences, an MSc in Parasitology, and a PhD in Health Sciences. He has been based at Statens Serum Institut, Copenhagen, since 2004. Since 2006, he has authored/co-authored more than 80 articles in international, peer-reviewed scientific journals. In 2013, he was awarded the Fritz Kauffmann Prize for his contribution to clinical microbiology in Denmark. For many years, he has been pursuing the role of common intestinal micro-eukaryotes in human health and disease. Follow Rune on Twitter @Eukaryotes.
World IBD Day (#worldIBDday) is observed on May 19 every year. This is the day for the millions of patients with IBD (inflammatory bowel disease), their supporters and IBD organizations worldwide to raise awareness, advance the understanding of the impact of IBD on human health and highlight the large number of people affected.
Ulcerative colitis and Crohn’s disease, the major types of IBD, are autoimmune diseases, the etiology of which appears multifactorial, involving both genetic and environmental factors. A study in the American Journal of Gastroenterology mapped the risk of acquiring IBD in relatives of patients with IBD.1 The study was based on data in the Danish National Patient Register, which included the 45,857 Danes who were diagnosed with IBD between 1977 and 2011. The team identified that the children, siblings or parents of individuals with IBD had an eightfold increased risk of developing IBD. For grandparents, uncles, aunts, nephews and nieces, the risk was increased by 2.5-fold. Among the younger siblings of patients with Crohn’s disease who were aged 20–25 years, the risk of developing IBD over the following 10 years was as high as 2%. First author on the paper, Frederik Trier Møller, says “Our results can be used in the counselling of relatives of IBD patients and maybe in the long run to identify persons, who could benefit from future available preventive measures.”
Moving on to environmental factors, the intestinal microbiota is thought also to have a key role in the development of IBD. Books, such as ‘An Epidemic of Absence,’2 sum up some of the hypotheses on the etiology of allergic and autoimmune diseases. Intestinal parasites—protists and worms—are eukaryotic symbionts associated with the human intestine that have co-evolved with humans over thousands of years. These symbionts are still almost obligate findings in citizens in some regions of the world where IBD appears to be a very limited problem (e.g. Sub-Saharan Africa). Such organisms tend to establish stable communities in the human gut, but their role in human health and disease remains relatively unexplored. However, there is some evidence that the defaunation of the human gut seen in many countries with a Westernized lifestyle is associated with an increased incidence of immune-mediated and inflammatory diseases.2–5 Hence, while busy ridding ourselves of bugs, maybe particularly so those of our children, we may have inflicted new diseases on ourselves, including IBD. And so, in efforts to ‘dirty up’ our diets again, potential alleviation of IBD using concoctions of microscopic helminth eggs (Trichuris suis) is currently being investigated, the rationale being that helminth therapy will favorably modulate pro-inflammatory cytokine responses associated with intestinal inflammation. Indeed, IBD patients appear much less prone to being hosts of parasites than healthy individuals,6 but until now, only mere associations have been identified, not mechanistic understandings.
Not only parasites—or the lack thereof—but also bacteria may have crucial roles in the etiology of IBD. It’s difficult not to think of peptic ulcers and gastric cancer when the word falls on Helicobacter pylori. Meanwhile, performing a meta-analysis of 33 available studies, comprising 4,400 IBD patients and 4,763 controls, to explore the association between H. pylori infection and IBD, Rokkas and colleagues7 found that 26.5% of IBD patients tested positive for H. pylori infection, compared with 44.7% of individuals in the control group. The significant negative association between H. pylori infection and IBD supports the hypothesis that H. pylori infection protects against the development of IBD. This conclusion is backed up by data in a recent study that was not included in the meta-analysis. Roka et al. found that the occurrence of H. pylori gastritis was less frequent in children with newly diagnosed IBD compared with controls.8 However, the team calls for studies that enable the distinction between a true protective role of H. pylori and a confounding effect due to, for instance, previous use of antibiotics in children with IBD.
The fact that patients with IBD may have a slightly higher risk of developing small bowel cancer and colorectal cancer than individuals without the disease may now be quite well established, but how about the treatment offered to IBD patients? For example, what are the side effects of biologics and how severe are they? A study published in JAMA aimed to investigate whether patients with IBD who were exposed to TNF-α antagonists were at increased risk of developing cancer.9 Exposure to TNF-α antagonists (e.g. infliximab, adalimumab, and certolizumab pegol) among patients with IBD was not associated with an increased risk of cancer over a median follow-up of 3.7 years; an increased risk associated with longer-term accumulated doses and follow-up, however, could not be excluded.
With regard to anti-TNF treatment and beyond, the ‘Therapy update: Best use of biologics in IBD in 2014’ session at UEG Week 2014 is available in the UEG Education Library. In the presentation, Professor Séverine Vermeire uses the ECCO guidelines and her experience to advise on when to use anti-TNF agents.10 Dr Silvio Danese then talks us through emerging therapeutic monoclonal antibodies, such as vedolizumab, golimumab, etrolizumab, tofacitinib, including their mechanisms of action.11 Dr Alessandro Armuzzi reviews the efficacy of drugs used for prevention of postoperative recurrence of Crohn’s disease recurrence, distinguishing between endoscopic and clinical recurrence, and highlights the importance of revisiting strategies to managing postoperative Crohn’s disease.12 In the final presentation from the session, Professor Gils highlights the importance of using pharmacokinetics to guide anti-TNF treatment in clinical practice.13 For more on the same topic, I guide your attention to the ‘How to manage IBD in 2014’ session from UEG Week 2014.
Professor Maria Abreu brings you the best on IBD from Digestive Disease Week 201414 and also provides a strategy for how to make a confident diagnosis of IBD15 in the collection of presentations from the postgraduate course ‘What is important when diagnosing IBD?’ This collection also includes Dr Shomron Ben-Horin asking the question ‘Do characteristics at diagnosis predict disease outcome and complications?’,16 something which is also to some extent taken up by Dr Geert D’Haens in a very ‘good-for-teaching’ talk that aims to answer the question ‘Is differentiating ulcerative colitis from Crohn’s disease important?’17
The IBD material available in the UEG Education Library is vast, and I can only encourage you to mark #worldIBDday2015 by listening to some of these presentations. Also, if you want to know more about the activities related to World IBD Day, you may want to visit the World IBD events page.
Finally, perhaps it is worth suggesting that World IBD Day should receive special attention on the Faroe Islands. This North-Atlantic archipelago has the highest incidence of IBD in the world, going from 8 per 100,000 person years in 1960–1979 to 75 per 100,000 person years in 2010–2014.18 Such a rapid change is most likely linked not only to increased diagnostic awareness but also to so-far-unidentified environmental factors.
References
- Moller FT, et al. Familial risk of inflammatory bowel disease: a population-based cohort study 1977–2011. Am J Gastroenterol 2015; 110: 564–571.http://www.nature.com/ajg/journal/v110/n4/full/ajg201550a.html
- Velasquez-Manoff M. An Epidemic of Absence: A New Way of Understanding Allergies and Autoimmune Diseases. New York: Scribner, 2013.
- Elliot DE, and Weinstock JV. Where are we on worms? Curr Opin Gastroenterol 2012; 28: 551–556. http://journals.lww.com/co-gastroenterology/pages/articleviewer.aspx?year=2012&issue=11000&article=00003&type=abstract
- Wiria AE, et al. Helminth infection in populations undergoing epidemiological transition: a friend or foe? Semin Immunopathol 2012; 34: 889–901. http://link.springer.com/article/10.1007%2Fs00281-012-0358-0
- Rook GA, et al. Microbial ’Old Friends’, immunoregulation and stress resilience. Evol Med Public Health 2013; 2013: 46–64. http://emph.oxfordjournals.org/content/2013/1/46.long
- Petersen AM et al. Active ulcerative colitis associated with low prevalence of Blastocystis and Dientamoeba fragilis infection. Scand J Gastroenterol 2013; 48: 638–639. http://informahealthcare.com/doi/abs/10.3109/00365521.2013.780094
- Rokkas T, et al. The association between Helicobacter pylori infection and inflammatory bowel disease based on meta-analysis. United European Gastroenterology Journal Epub ahead of print April 9 2015. DOI:10.1177/2050640615580889. http://ueg.sagepub.com/content/early/2015/03/31/2050640615580889.full
- Roka K, et al. The prevalence of Helicobacter pylori gastritis in newly diagnosed children with inflammatory bowel disease. Helicobacter 2014; 19: 400–405.http://onlinelibrary.wiley.com/doi/10.1111/hel.12141/abstract
- Nyboe Andersen N, et al. Association between tumor necrosis factor-α antagonists and risk of cancer in patients with inflammatory bowel disease. JAMA 2014; 311: 2406–2413.http://jama.jamanetwork.com/article.aspx?articleid=1881309
- Vermeire S. When should we start anti-TNF in IBD? Presentation in the “Therapy update: Best use of biologics in IBD in 2014” session at UEG Week 2014.https://www.ueg.eu/education/document-detail/?file=109113
- Danese S. Looking beyond anti-TNF in IBD: Vedolizumab, tofacitinib, etc. Presentation in the “Therapy update: Best use of biologics in IBD in 2014” session at UEG Week 2014.https://www.ueg.eu/education/document-detail/?file=109114
- Armuzzi A. Anti-TNF to prevent and treat postoperative recurrence of Crohn’s disease. Presentation in the “Therapy update: Best use of biologics in IBD in 2014” session at UEG Week 2014. https://www.ueg.eu/education/document-detail/?file=109117
- Gils A. Use of pharmacokinetics to guide anti-TNF treatment in clinical practice. Presentation in the “Therapy update: Best use of biologics in IBD in 2014” session at UEG Week 2014https://www.ueg.eu/education/document-detail/?file=109120
- Abreu MT. Inflammatory bowel disease. Presentation in the “Best of DDW” session at UEG Week 2014.https://www.ueg.eu/education/document-detail/?file=108987
- Abreu MT. Diagnostic strategy to make a confident diagnosis of IBD. Presentation at UEG Week 2014. Presentation in the Postgraduate Teaching Programme at UEG Week 2014. https://www.ueg.eu/education/document-detail/?file=108807
- Ben-Horin S. Do characteristics at diagnosis predict disease outcome and complications? Presentation in the Postgraduate Teaching Programme at UEG Week 2014.https://www.ueg.eu/education/document-detail/?file=108808
- d’Haens G. Is differentiating UC from CD important? Presentation in the Postgraduate Teaching Programme at UEG Week 2014.https://www.ueg.eu/education/document-detail/?file=108809
- Hammer T et al. DOP010 Incidence of inflammatory bowel diseases in the Faroe Islands from 1960–2014: a 54-year overview from a population-based cohort. Presentation in “DOP Session 2 – Epidemiology of IBD" at ECCO Congress 2015.https://www.ecco-ibd.eu/index.php/publications/congress-abstract-s/abstracts-2015/item/dop010-incidence-of-inflammatory-bowel-diseases-in-the-faroe-islands-from-1960-2014-a-54-year-overview-from-a-population-based-cohort.html
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