Dietary iron and heme, likely through their effect on gut commensal bacteria and colonic barrier function, have been shown to modulate colonic inflammation in animal models of colitis. Nonetheless, ...the link between dietary total and heme iron and risk of Crohn's disease (CD) and ulcerative colitis (UC) has not been previously explored.
We conducted a prospective cohort study of 165,331 U.S. women enrolled in the Nurses' Health Study and Nurses' Health Study II. Dietary information was collected using a validated food frequency questionnaire at baseline (1984) and updated every 2 to 4 years. Self-reported CD and UC diagnoses were confirmed through medical records review. We used Cox proportional hazard models to calculate hazard ratios and 95% confidence intervals while adjusting for potential confounders. In a case-control study nested within these cohorts, we evaluated the interaction between single-nucleotide polymorphisms associated with genome-wide susceptibility to CD and UC and dietary total and heme iron intake on risk of CD and UC using logistic regression modeling.
Through 2011, over 3,038,049 person-years of follow-up, we documented 261 incident cases of CD and 321 incident cases of UC. Dietary heme iron was nonsignificantly associated with increased risk of UC (Ptrend = 0.12). This association seemed to be modified by the UC susceptibility locus, rs1801274, a coding variant in the FcγRIIA gene (Pinteraction = 7.00E-05). In contrast, there was no association between dietary heme iron and risk of CD (Ptrend = 0.67). We also did not observe an association between total dietary intake of iron and risk of CD or UC (All Ptrend > 0.35).
In 2 large prospective cohort studies, dietary total and heme iron were not associated with risk of CD or UC. Our suggestive finding that the association between dietary heme iron intake and risk of UC may be modified by a coding variant in FcγRIIA gene warrants additional investigation.
Acute severe ulcerative colitis (ASUC) is a serious complication of ulcerative colitis (UC). Management of partial responders to steroids or rescue therapy remains challenging. Whether there is a ...role for re-look sigmoidoscopic evaluation in disease management is unknown.
Our study cohort consisted of patients who underwent 2 sigmoidoscopic procedures during the same index hospitalization for ASUC at our center. Reasons for repeat endoscopic evaluation and endoscopic and histologic severity of inflammation during both procedures were noted. Multivariable regression models were performed to identify predictors of improvement at the second endoscopic assessment and to determine the independent effect of such an improvement on in-hospital colectomy and at 3, 6, and 12 months.
Our study included 49 patients (mean age, 42 years; 52% women). Just under one-third of patients (30%) were noted to have improved endoscopic appearance at the second sigmoidoscopy, at a median of 9 days after initial exam. None of the patients who had improvement on the second endoscopy underwent in-hospital colectomy, compared with 46% of those with worsening or persistent disease (P = 0.002). Similar differences in the improved group persisted at 3 months (P = 0.007) and 6 months (P = 0.027). Histologic severity at the first endoscopy was associated with increased risk of colectomy in-hospital (odds ratio, 3.8; 95% confidence interval, 1.02-14.21) and at 3 and 6 months.
After a median interval of 9 days, endoscopic improvement was noted in 30% of patients with ASUC undergoing a second sigmoidoscopy, which predicted lower rates of colectomy in-hospital and at 3 and 6 months.
Recent epidemiologic studies have shown that although the incidence of inflammatory bowel disease (IBD) is rapidly increasing in newly industrialized countries, at the turn of the 21st century the ...incidence had stabilized in the Western world. In this issue of Inflammatory Bowel Diseases, Torabi and colleagues present their findings on the temporal trends and geographic variations in IBD incidence in Manitoba from 1990 to 2012 using the Manitoba Health population registry and the University of Manitoba IBD epidemiology database. Their results demonstrate an overall decrease in the incidence of IBD during the study period. They also found significant regional variations in disease incidence within Manitoba, with rates of new diagnosis of IBD remaining high in several regions. Lastly, the study found that a higher proportion of the indigenous population had a lower rate of IBD. These findings provide new insights on the changing epidemiology of IBD in the Western world. The overall declining incidence of IBD and identification of persistently low and high-risk populations in Manitoba, which traditionally has had some of the highest incidence rates of IBD, is intriguing and can provide new avenues of research for epidemiologists in the field.
In addition to cholesterol depletion, statins also significantly decrease systemic inflammation as measured by C-reactive protein. In this issue of American Journal of Gastroenterology, Ungaro et al. ...present their results on the associations between statin prescriptions and risk of Crohn's disease (CD) and ulcerative colitis (UC). Using a national medical claims and pharmacy database created by Symphony Health Solutions LLC (SHA), they show that any use of statin is protective against diagnosis of CD and UC. The protective effect against CD appears strongest among older populations (>60 years old). These findings offer intriguing insights into inflammatory pathways that could be modulated by cholesterol lowering drugs. In addition, if replicated in other cohorts, these results provide further rationale for investigating the use of statins in broader preventive efforts, including healthy patients at risk of developing inflammatory bowel disease.
Oral contraceptive (OC) use has been consistently linked to increased risk of inflammatory bowel disease. Nonetheless, a specific role of OC in the natural history of ulcerative colitis (UC) is ...unknown.
We identified 6,104 incident female UC cases aged 16-51 years at diagnosis from the Swedish National Patient Register starting in January of 2003. Information on current OC use was obtained from the Prescribed Drug Register starting in July of 2005. We followed cases through December of 2014 for primary outcome defined as first UC-related surgery, and the secondary outcomes defined by recipient of the first prescription of oral steroids or anti-tumor necrosis factor (anti-TNF) use. We used Cox proportional hazard modeling with time-varying covariates to estimate multivariable-adjusted hazard ratio (aHR) and 95% confidence interval (CI).
Over 31,421 person-years of follow up, we observed 162 cases of UC-related surgery. Compared with nonusers, current and past use of OC were not significantly associated with risk of UC-related surgery (aHR=0.79; 95% CI, 0.52-1.18; and aHR=0.74, 95% CI, 0.46-1.18, respectively). The association did not appear to be modified by type of OC use (progestin-only vs. combination of progestin and estrogen), longer duration of use, or higher number of dispensed prescriptions (All P
>0.28). Similarly, longer use or higher cumulative number of OC prescriptions were not associated with increased risk of receiving a steroid prescription (P
=0.68 and 0.63, respectively). In exploratory analyses restricted to Stockholm county, current OC use was not associated with increased risk of receiving anti-TNF therapy (aHR=0.83, 95% CI, 0.59-1.18).
In a large nationwide registry of UC patients, we found no association between OC use and UC progression. Our data offer reassurance regarding the safety of OC assessed by its effect on risk of surgery and steroid or anti-TNF use in women with established UC.
LINKED CONTENT
This article is linked to Casey et al papers. To view these articles, visit https://doi.org/10.1111/apt.16731 and https://doi.org/10.1111/apt.16815
The long-term natural history of microscopic colitis (MC) (collagenous colitis (CC), lymphocytic colitis (LC)), traditionally considered relapsing but non-progressive diseases, is poorly defined. ...Whether persistent histologic inflammation in such diseases is associated with an increased risk of colorectal neoplasia (CRN) or extracolonic cancers has not been robustly established.
This retrospective cohort included diagnosed with MC at a referral center. Rates of CRN and extracolonic cancer were compared to patients undergoing screening colonoscopy (n = 306) and to the United States population using data from the Surveillance, Epidemiology, and End-Results (SEER) program. Standardized incidence ratios (SIR) and 95% confidence intervals were calculated and multivariable regression models used to identify the effect of MC diagnosis and severity on cancer risk.
Our study included 221 patients with microscopic colitis (112 CC, 109 LC) among whom 77% were women. Compared to the colonoscopy control population, MC was associated with similar odds of tubular adenoma (Odds ratio (OR) 1.07, 95% CI 0.69-1.66) or villous adenoma (OR 1.26, 95% CI 0.17-9.42). Compared to patients with a single episode of MC, those with 2 or more episodes had similar risk of colon cancer (OR 0.83, 95% CI 0.20-3.39) or tubular adenoma (OR 1.49 95% CI 0.83-2.67). We also identified no statistical increase in the rates of cancer in the MC population compared to US-SEER data.
Microscopic colitis was not associated with increased risk of CRN and extracolonic cancers when compared to controls undergoing colonoscopy or the US SEER population.
Antibiotic use has emerged as a risk factor for colorectal neoplasia and is hypothesized as a contributor to the rising incidence of colorectal cancer under age 50 years or early-onset colorectal ...cancer (EOCRC). However, the impact of antibiotic use and risk of EOCRC is unknown.
We conducted a population-based case-control study of CRC among individuals aged ≥18 years in the Epidemiology Strengthened by histoPathology Reports in Sweden (ESPRESSO) cohort (2006-2016). The primary outcome was EOCRC. A secondary outcome was CRC at any age. Incident CRC was pathologically confirmed, and for each, up to 5 population-based controls were matched on age, sex, county of residence, and calendar year. We assessed prescriptions until 6 months before CRC diagnosis. Conditional logistic regression was used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs).
We identified 54,804 cases of CRC (2,557 EOCRCs) and 261,089 controls. Compared with none, previous antibiotic use was not associated with EOCRC risk after adjustment for potential confounders (aOR 1.06, 95% CI: 0.96, 1.17) with similarly null findings when stratified by anatomic tumor site. In contrast, previous antibiotic use was weakly associated with elevated risk for CRC at any age (aOR 1.05, 95% CI: 1.02, 1.07). A potential but modest link between broad-spectrum antibiotic use and EOCRC was observed (aOR 1.13, 95% CI: 1.02, 1.26).
We found no conclusive evidence that antibiotics are associated with EOCRC risk. Although antibiotic use was weakly associated with risk of CRC at any age, the magnitude of association was modest, and the study period was relatively short.
Bisphosphonates are used for the treatment of bone metastases and have been associated with a lower risk of breast cancer. A recent case-control study showed an inverse association between ...bisphosphonate use and colorectal cancer. Data from prospective cohorts are lacking.
We prospectively examined the relationship between bisphosphonate use and risk of colorectal cancer among 86,277 women enrolled onto the Nurses Health Study (NHS). Since 1998, participants have returned biennial questionnaires in which they were specifically queried about the regular use of bisphosphonates. We used Cox proportional hazards models to calculate hazard ratios (HRs) and 95% CIs for risk of colorectal cancer.
Through 2008, we documented 801 cases of colorectal cancer over 814,406 person-years of follow-up. The age-adjusted HR for women who regularly used bisphosphonates was 0.92 (95% CI, 0.73 to 1.14) and was further attenuated after adjustment for other risk factors (multivariate HR, 1.04; 95% CI, 0.82 to 1.33). The risk was not influenced by duration of use (P(trend) = 0.79). Compared with nonusers, the multivariate-adjusted HRs of colorectal cancer were 1.24 (95% CI, 0.94 to 1.64) for women with 1 to 2 years of use, 1.16 (95% CI, 0.79 to 1.69) for 3 to 4 years of use, and 0.97 (95% CI, 0.60 to 1.56) for ≥ 5 years of use. There was no association between bisphosphonate use and colorectal cancer within strata of other risk factors.
In a large prospective cohort, we did not observe an association between long-term use of bisphosphonates and risk of colorectal cancer.
Recent animal studies have identified that dietary salt intake may modify the risk and progression of autoimmune disorders through modulation of the IL-23/T
17 pathway, which is critical in the ...pathogenesis of ulcerative colitis (UC) and Crohn's disease (CD).
We conducted a prospective study of U.S. women enrolled in the Nurses' Health Study (NHS) and NHSII who provided detailed and validated information on diet and lifestyle beginning in 1984 in NHS and 1991 in NHSII. We confirmed incident cases of UC and CD reported through 2010 in NHS and 2011 in NHSII. We used Cox proportional hazards models to calculate hazard ratios and 95% confidence intervals. In a case-control study nested within these cohorts, we evaluated the interaction between single nucleotide polymorphisms (SNPs) in genes involved in T
17 pathway and dietary potassium on risk of CD and UC. In a cohort of healthy volunteers, we also assessed the effect of supplemental potassium on development of naïve and memory T cells, differentiated with TGFβ1 or T
17 conditions.
Among a total of 194,711 women over a follow-up of 3,220,247 person-years, we documented 273 cases of CD and 335 cases of UC. Dietary intake of potassium (
= 0.005) but not sodium (
= 0.44) was inversely associated with risk of CD. Although, both dietary potassium and sodium were not significantly associated with risk of UC, there was a suggestion of an inverse association with dietary potassium (
= 0.08). The association of potassium with risk of CD and UC appeared to be modified by loci involved in the T
17 pathway that have previously been associated with susceptibility to CD, particularly SNP rs7657746 (
) (
= 0.004 and 0.01, respectively).
, potassium enhanced the expression of Foxp3 in both naïve and memory CD4+ T cells
activating Smad2/3 and inhibiting Smad7 in T
17 cells.
Dietary potassium is inversely associated with risk of CD with both
and gene-environment interaction data suggesting a potential role for potassium in regulating immune tolerance through its effect on Tregs and T
17 pathway.
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