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

Ananthakrishnan, Ashwin N.; Cagan, Andrew; Gainer, Vivian S.; Cheng, Su–Chun; Cai, Tianxi; Szolovits, Peter; Shaw, Stanley Y.; Churchill, Susanne; Karlson, Elizabeth W.; Murphy, Shawn N.; Kohane, Isaac S.; Liao, Katherine P.

doi:10.1111/apt.12706

Cited by 57 publications

(35 citation statements)

References 44 publications

(105 reference statements)

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“…The effect of vitamin D does not appear to be restricted to disease activity alone. We also demonstrated the IBD patients with low plasma vitamin D may have increased risk of cancers, in particular colorectal cancer, and clostridium difficile infection 58, 59 suggesting a panoply of adverse health outcomes associated with low vitamin D levels in patients with IBD. As most of the literature on vitamin D and IBD has been observational in nature and retrospective, it has been hypothesized that vitamin D deficiency may merely be a marker of severe disease and a confounder rather than a true biologic mediator.…”

Section: Environmental Risk Factorsmentioning

confidence: 70%

Environmental Risk Factors for Inflammatory Bowel Diseases: A Review

2014

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Inflammatory bowel diseases (IBD) comprising Crohn’s disease (CD) and ulcerative colitis (UC) are chronic immunologically mediated diseases. The key mechanism underlying the pathogenesis of these diseases is a dysregulated immune response to commensal flora in a genetically susceptible host. Thus intestinal microbial dysbiosis, host genetics, and the external environment all play an important role in the development of incident disease and in determining subsequent disease behavior and outcomes. There are several well-defined or putative environmental risk factors including cigarette smoking, appendectomy, diet, stress and depression, vitamin D as well as hormonal influence. The effect of some of the risk factors appears to differ between CD and UC suggesting that despite shared genetic and immunologic mechanisms, distinct pathways of pathogenesis exist. There is a growing body of literature identifying risk factors for incident disease. There is less rigorous literature defining triggers of relapse, and few controlled clinical trials examining if modification of such risk factors results in an improvement in patient outcomes. This is an area of considerable patient, physician, and scientific interest, and there is an important unmet need for rigorous studies of the external environment in disease pathogenesis and subsequent course.

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Section: Environmental Risk Factorsmentioning

confidence: 70%

Environmental Risk Factors for Inflammatory Bowel Diseases: A Review

2014

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“…2,3 We also included all antibiotic exposures in the year prior to infection, age, and vitamin D deficiency, all which have been linked to risk of infection. 5,7 Patients were matched using the protocol outlined in FIGURE 1, which features a rolling propensity score matching process over time beginning with study participants who had their first CDI event in 2010. Matching was done without replacement to build a 1:2 (cases:controls) cohort.…”

Section: Materials and Methods And Designmentioning

confidence: 99%

“…1 Previous research has shown that the likelihood of infection is increased by many factors including, but not limited to, healthcare system contact, nutritional deficiencies, and antibiotic exposure. 2–5 CDI is an increasingly prevalent infectious complication in the IBD patient population. 6–8 CDI in IBD patients is associated with higher rates of hospitalization, surgery, longer hospital stays, increased healthcare charges, and, most importantly, an increased mortality.…”

Section: Introductionmentioning

confidence: 99%

Lasting Impact of Clostridium difficile Infection in Inflammatory Bowel Disease

Anderson

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Ramos-Rivers

et al. 2017

Inflammatory Bowel Diseases

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Background Inflammatory bowel disease (IBD) patients are at an increased risk of Clostridium difficile infection (CDI), but the impact of CDI on disease severity is unclear. The aim of this study was to determine the effect of CDI on long-term disease outcome in a matched cohort of IBD patients. Methods Patients who tested positive for infection formed the CDI positive group. We generated a 1:2 propensity matched case to control cohort based on risk factors of CDI in the year prior to infection. Healthcare utilization data (emergency department use, hospitalizations, telephone encounters), medications, labs, disease activity and quality of life (QOL) metrics were compared by CDI status. Results A total of 198 patients (66 CDI, 132 matched controls) were included (56.6% female; 60.1% Crohn’s disease, 39.9% ulcerative colitis). In the year of infection, having CDI was significantly associated with more steroid and antibiotic exposure, elevated C-reactive protein or erythrocyte sedimentation rate, low vitamin D, increased disease activity, worse QOL, and increased healthcare utilization (all p<0.01). During the next year after infection, CDI patients continued to have increased exposure to CDI targeted antibiotics (p<0.001) and other antibiotics (p=0.02). They also continued to have more clinic visits (p=0.02), telephone encounters (p=0.001), and increased healthcare financial charges (p=0.001). Conclusions CDI in IBD is significantly associated with markers of disease severity, increased healthcare utilization and poor QOL during the year of infection, and a five-fold increase in healthcare charges in the year following infection.

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“…Other recent studies in humans have demonstrated that 1,25(OH) 2 D 3 may directly interact with the gut microbiota and ameliorate dysbiosis in autoimmune patients (68). In a cohort of 3,188 IBD patients, higher plasma 25(OH)D 3 (27.1 ng/mL) was associated with significantly reduced risk of Clostridium difficile infection (68).…”

Section: Discussionmentioning

confidence: 99%

“…In a cohort of 3,188 IBD patients, higher plasma 25(OH)D 3 (27.1 ng/mL) was associated with significantly reduced risk of Clostridium difficile infection (68). Another study in MS patients showed that supplementing with 5,000 IU of vitamin D per day for 90 days increased the abundance of Akkermansia , which promotes immune tolerance, as well as Faecalibacterium and Coprococcus , which both produce butyrate, an anti-inflammatory SCFA (69).…”

Section: Discussionmentioning

confidence: 99%

Role of Vitamin D in the Hygiene Hypothesis: The Interplay between Vitamin D, Vitamin D Receptors, Gut Microbiota, and Immune Response

2016

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The hygiene hypothesis postulates that higher levels of cleanliness and improper exposure to microorganisms early in childhood could disturb the intestinal microbiome resulting in abnormal immune responses. Recently, more attention has been put on how a lack of sun exposure and consequently vitamin D deficiency could lead to less immune tolerance and aberrant immune responses. Moreover, vitamin D receptor (VDR) function has been positioned to be a critical aspect of immune response and gut homeostasis. Therefore, this review focuses on the role that the interaction between vitamin D, VDR function, and gut microbiome might have on autoimmune diseases in the context of the hygiene hypothesis. Literature shows that there is a high correlation between vitamin D deficiency, VDR dysfunction, gut microbiota composition, and autoimmune diseases. The biologically active form of vitamin D, 1,25(OH)2D3, serves as the primary ligand for VDRs, which have been shown to play a fundamental role in reducing autoimmune disease symptoms. Although the biological functions of VDR, the effects of its genetic variants, and the effects of epigenetic profiles in its promoter region are largely unknown in humans, studies in murine models are increasingly demonstrating that VDRs play a crucial role in attenuating autoimmune disease symptoms by regulating autophagy and the production of antimicrobial peptides, such cathelicidin and β-defensin, which are responsible for modifying the intestinal microbiota to a healthier composition. Remarkably, evidence shows that hormonal compounds and byproducts of the microbiota such as secondary bile acids might also activate VDR. Therefore, understanding the interaction between VDR and gut microbiota is of the utmost importance toward understanding the rise in autoimmune diseases in Western countries. We have gained insights on how the VDR functions affects inflammation, autophagy, and microbiota composition that could lead to the development of pathogenesis of autoimmune diseases, while confirming the role vitamin D and VDRs have in the context of hygiene hypothesis.

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

Cited by 57 publications

References 44 publications

Environmental Risk Factors for Inflammatory Bowel Diseases: A Review

Environmental Risk Factors for Inflammatory Bowel Diseases: A Review

Lasting Impact of Clostridium difficile Infection in Inflammatory Bowel Disease

Role of Vitamin D in the Hygiene Hypothesis: The Interplay between Vitamin D, Vitamin D Receptors, Gut Microbiota, and Immune Response

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