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Antibiotics Associated With Increased Risk of New-onset Crohn's Disease but not Ulcerative Colitis

http://www.medscape.com/viewarticle/835254

A Meta-analysis

Ryan Ungaro MD, Charles N Bernstein MD, Richard Gearry MB ChB, PhD, Anders Hviid MSc, Kaija-Leena Kolho MD, PhD, Matthew P Kronman MD, MSCE, Souradet Shaw MSc, Herbert Van Kruiningen MD, Jean-Frédéric Colombel MD, PhD, Ashish Atreja MD, MPHDisclosures
Am J Gastroenterol. 2014;109(11):1728-1738.

Abstract

Objectives The objective of this study was to perform a meta-analysis investigating Antibiotic exposure as a risk factor for developing inflammatory bowel disease (IBD).

Methods A literature search using Medline, Embase, and Cochrane databases was performed to identify studies providing data on the association between Antibiotic use and newly diagnosed IBD. Included studies reported Crohn's disease (CD), ulcerative colitis (UC), or a composite of both (IBD) as the primary outcome and evaluated Antibiotic exposure before being diagnosed with IBD. A random-effects meta-analysis was conducted to determine overall pooled estimates and 95% confidence intervals (CIs).

Results A total of 11 observational studies (8 case–control and 3 cohort) including 7,208 patients diagnosed with IBD were analyzed. The pooled odds ratio (OR) for IBD among patients exposed to any antibiotic was 1.57 (95% CI 1.27–1.94). Antibiotic exposure was significantly associated with CD (OR 1.74, 95% CI 1.35–2.23) but was not significant for UC (OR 1.08, 95% CI 0.91–1.27). Exposure to Antibiotics most markedly increased the risk of CD in children (OR 2.75, 95% CI 1.72–4.38). All Antibiotics were associated with IBD, with the exception of penicillin. Exposure to metronidazole (OR 5.01, 95% CI 1.65–15.25) or fluoroquinolones (OR 1.79, 95% CI 1.03–3.12) was most strongly associated with new-onset IBD.

Conclusions Exposure to antibiotics appears to increase the odds of being newly diagnosed with CD but not UC. This risk is most marked in children diagnosed with CD.

Introduction

Environmental factors have a key role in the pathogenesis of inflammatory bowel disease (IBD). Monozygotic twins have at most a 50% concordance rate of disease.[1] Furthermore, the incidence of IBD has been increasing worldwide over time. Developing countries have seen an increase in IBD incidence as they have Westernized.[2] Immigrants from areas with a low incidence of IBD who move to areas with high incidence appear to be at an increased risk of IBD.[3]

Emerging evidence suggests that certain medications are associated with an increased risk of new-onset IBD. In particular, antibiotics have been linked to the development of both Crohn's disease (CD) and ulcerative colitis (UC).[4] Growing research suggests that the microbiome and its interaction with the mucosal immune system are important in the pathogenesis of IBD.[5] Antibiotics can cause alterations to the microbiome that may potentially contribute to the dysbiosis and dysregulated immune response seen in IBD.[6] Another possibility is that antibiotics are actually a marker for a separate IBD environmental risk factor such as enteric infections.[7]

Previous studies have investigated the association of antibiotic exposure with newly diagnosed IBD in both adult and pediatric populations.[8–12] CD has been more consistently associated with antibiotic use, with some studies demonstrating an increased risk of CD but not UC.[8,13–15] It also appears that patients who receive more frequent courses of antibiotics have a higher likelihood of developing IBD.[10,12] It is unclear whether certain antibiotics are more strongly associated with IBD, as few studies have reported data on specific antibiotic classes.[11,15–17] However, the relationship between exposure to antibiotics and new-onset IBD is not uniform, as some studies have found no association.[18,19]

To better understand the association between antibiotic exposure and new-onset IBD, we conducted a meta-analysis to investigate antibiotics as a risk factor for developing IBD. Our other principal aims were to determine whether the effect of antibiotics is different in children compared with adults and to evaluate whether specific antibiotic classes are associated with new-onset IBD.