835 Genetic Risk Factors for Clostridium difficile Infection in Ulcerative Colitis

Ananthakrishnan, Ashwin N.; Oxford, Emily C; Nguyen, Deanna D.; Sauk, Jenny; Yajnik, Vijay; Xavier, Ramnik J.

doi:10.1016/s0016-5085(13)60530-2

Cited by 15 publications

(20 citation statements)

References 36 publications

(47 reference statements)

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“…In one study of 319 patients with known UC, 6 IBD‐risk loci were associated with an increased risk of Clostridioides difficile infection (CDI), while 2 risk loci were protective 75 . Genetic risk alleles explained a larger proportion of the variance in CDI risk than clinical factors, suggesting that host immunity is also a fundamental player in CDI susceptibility 75 . These data support the hypothesis that CDI might be relevant in IBD pathogenesis.…”

Section: Discussionmentioning

confidence: 83%

“…With respect to the latter because the clinical symptoms of gastroenteritis and IBD overlap, there is inconsistent utilisation of diagnostic testing and the data are subject to bias, heterogeneity and unmeasured confounders, such as nongenetic and genetic factors underlying differential susceptibility. In one study of 319 patients with known UC, 6 IBD‐risk loci were associated with an increased risk of Clostridioides difficile infection (CDI), while 2 risk loci were protective 75 . Genetic risk alleles explained a larger proportion of the variance in CDI risk than clinical factors, suggesting that host immunity is also a fundamental player in CDI susceptibility 75 .…”

Section: Discussionmentioning

confidence: 99%

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Systematic review: gastrointestinal infection and incident inflammatory bowel disease

Axelrad

Cadwell

Colombel

et al. 2020

Aliment Pharmacol Ther

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Background: The initiating events of chronic gastrointestinal (GI) inflammation inCrohn's disease (CD) and ulcerative colitis (UC) are not well-defined, but GI infections are implicated. Aims:To define the role of GI infections in risk of incident inflammatory bowel disease (IBD) and synthesise the current body of relevant translational data to provide biological context for associations between GI infections and IBD risk. Methods:We systematically reviewed electronic databases through February 2020.Clinical studies that provided risk estimates of the association between GI infections and incident IBD were included. Inclusion criteria were broader for translational studies aiming to define mechanisms of GI infections and predisposition to or protection from IBD. Results: Of the studies identified, 63 met full inclusion criteria. Among studies of clinical gastroenteritis, bacteria-specifically, Salmonella species, Campylobacter species and Clostridioides difficile-demonstrated consistent positive associations with risk of incident IBD. Of viruses, norovirus was associated with increased risk of incident CD. Regarding inverse associations with incident IBD, Helicobacter pylori and helminth infections were associated with a generally consistent reduced risk of IBD. Based on a qualitative analysis of the translational data, putative mechanisms involve multiple microbial and immunologic pathways. Conclusions: Based on this systematic review, certain enteric pathogens are associated with an increased risk of incident IBD, while others are potentially protective.Prospective studies are required to clarify the clinical implications of these enteric pathogens on the risk and course of IBD, and possible therapeutic or preventative benefit. | 1223 AXELRAD Et AL.

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Section: Discussionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Systematic review: gastrointestinal infection and incident inflammatory bowel disease

Axelrad

Cadwell

Colombel

et al. 2020

Aliment Pharmacol Ther

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“…19 In a previous study, our group demonstrated an association between a SNP on chromosome 7 associated with the gene CREB5 and increased risk for CDI in UC patients. 21 The CREB protein competes for binding to the cathelicidin promoter sequence and regulates its expression. In an earlier study, human alpha-defensins inhibited the effect of C. difficile toxin B 31 ; adequate levels of 25(OH)D are essential for production of human defensins, further supporting a mechanistic association between 25(OH)D and CDI.…”

Section: Discussionmentioning

confidence: 99%

“…19 Furthermore, a prior study from our group examining genetic risk factors for CDI demonstrated an association with a single nucleotide polymorphism (SNP) on chromosome 7 associated with CREB5, a member of the cyclic AMP responsive element-binding protein family associated with expression of the cathelicidin promoter sequence. 20,21 Consequently, we performed this study to examine whether plasma calcifediol, 25-hydroxy vitamin D [25 (OH)D] is associated with risk of subsequent CDI in a large multi-institutional cohort of patients with CD and UC. Identifying such an association will provide important insights into pathogenesis of CDI as well as suggest a role for vitamin D in the treatment of CDI.…”

Section: Introductionmentioning

confidence: 99%

Higher plasma vitamin D is associated with reduced risk of Clostridium difficile infection in patients with inflammatory bowel diseases

Ananthakrishnan

Cagan

Gainer

et al. 2014

Aliment Pharmacol Ther

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Introduction Patients with inflammatory bowel diseases (IBD) have an increased risk of clostridium difficile infection (CDI). Cathelicidins are anti-microbial peptides that attenuate colitis and inhibit the effect of clostridial toxins. Plasma 25(OH)D stimulates production of cathelicidins. Aim To examine the association between plasma 25(OH)D and CDI in patients with IBD Methods From a multi-institutional IBD cohort, we identified patients with at least one measured plasma 25(OH)D. Our primary outcome was development of CDI. Multivariate logistic regression models adjusting for potential confounders were used to identify independent effect of plasma 25(OH)D on risk of CDI. Results We studied 3,188 IBD patients whom 35 patients developed CDI. Patients with CDI-IBD were older and had greater co-morbidity. The mean plasma 25(OH)D level was significantly lower in patients who developed CDI (20.4ng/ml) compared to non-CDI IBD patients (27.1ng/mL) (p=0.002). On multivariate analysis, each 1ng/ml increase in plasma 25(OH)D was associated with a 4% reduction in risk of CDI (OR 0.96, 95% CI 0.93 – 0.99, p = 0.046). Compared t o individuals with vitamin D > 20ng/mL, patients with levels < 20ng/mL were more likely to develop CDI (OR 2.27, 95% CI 1.16 – 4.44). The mean plasma 25(OH)D in patients with CDI who subsequently died was significantly lower (12.8+8.1ng/ml) compared to those who were alive at the end of follow-up (24.3+13.2ng/ml) (p=0.01). Conclusion Higher plasma 25(OH)D is associated with reduced risk of C difficile infection in patients with IBD. Further studies of therapeutic supplementation of vitamin D in IBD-CDI patients may be warranted.

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“…The association between C. difficile and IBD is mediated by several factors such as the use of therapeutic drugs (including antibiotics), which alter the colonic flora, together with decreased immune status, and genetic predisposition (37), all favoring CDI. C. difficile affects the tissue through toxin production.…”

Section: Pathogenesismentioning

confidence: 99%

Clostridium difficile infection and inflammatory bowel disease

Cojocariu

Stanciu

Stoica³

et al. 2020

Turk J Gastroenterol

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Over the past 15 years, Clostridium difficile infection (CDI) in patients with inflammatory bowel disease (IBD) has increased both in incidence and severity. Traditional risk factors for CDI are similar in IBD and non-IBD populations, but there is a significant proportion of IBD patients which have distinctive characteristics. Patients with ulcerative colitis (UC) are more susceptible to CDI and have more severe outcomes than those with Crohn's disease (CD). CDI may be difficult to distinguish from an IBD flare due to similar clinical presentation, and therefore screening for CDI is recommended at every flare in such patients. Several studies showed worse clinical outcomes in IBD patients with CDI, including longer hospital stay, higher colectomy and mortality rates than in those without CDI. Vancomycin and metronidazole appear to have similar efficacy in patients with moderate disease, but vancomycin is preferred in severe disease. Measures must be taken to prevent the spread of infection. Clinicians should have a high index of suspicion for CDI when evaluating a patient with IBD flare, as rapid detection and prompt treatment of infection improve outcomes. This review summarizes the available literature on epidemiology, risk factors, clinical aspects, diagnostic methods, treatment, outcome, and prevention of CDI in IBD patients.

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835 Genetic Risk Factors for Clostridium difficile Infection in Ulcerative Colitis

Cited by 15 publications

References 36 publications

Systematic review: gastrointestinal infection and incident inflammatory bowel disease

Systematic review: gastrointestinal infection and incident inflammatory bowel disease

Higher plasma vitamin D is associated with reduced risk of Clostridium difficile infection in patients with inflammatory bowel diseases

Clostridium difficile infection and inflammatory bowel disease

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