The causes of obesity, other than genes and environment, are poorly understood. A recent study showed that exposure of mice to antibiotics in early life induced lasting effects on body composition ...owing to alteration of the intestinal microbiota.
Obesity is a major health issue worldwide, but the background for this condition is more complex than commonly assumed. Dietary and genetic factors have but partial roles in the development of obesity, which is why the focus in recent years has turned to the trillions of microbes residing in the human intestine and their possible effect on energy harvest and metabolic signaling. A study by Cox and colleagues
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showed that the administration of low-dose penicillin in early life induces lasting effects on body composition by altering the intestinal microbiota.
Early life is a critical period both for the establishment of . . .
Intestinal inflammation has been suggested to play a role in development of Parkinson's disease (PD) and multiple system atrophy (MSA). To test the hypothesis that IBD is associated with risk of PD ...and MSA, we performed a nationwide population-based cohort study.
The cohort consisted of all individuals diagnosed with IBD in Denmark during 1977-2014 (n=76 477) and non-IBD individuals from the general population, who were comparable in terms of gender, age and vital status (n=7 548 259). All cohort members were followed from IBD diagnosis/index date to occurrence of PD and MSA (according to the Danish National Patient Register).
Patients with IBD had a 22% increased risk of PD as compared with non-IBD individuals (HR=1.22; 95% CI 1.09 to 1.35). The increased risk was present independently of age at IBD diagnosis, gender or length of follow-up. The overall incidence of MSA was low in our study, and the regression analysis suggested a tendency towards higher risk of developing MSA in patients with IBD as compared with non-IBD individuals (HR=1.41; 95% CI 0.82 to 2.44). Estimates were similar for women and men. The increased risk of parkinsonism was significantly higher among patients with UC (HR=1.35; 95% CI 1.20 to 1.52) and not significantly different among patients with Crohn's disease (HR=1.12; 95% CI 0.89 to 1.40).
This nationwide, unselected, cohort study shows a significant association between IBD and later occurrence of PD, which is consistent with recent basic scientific findings of a potential role of GI inflammation in development of parkinsonian disorders.
Estimates of familial risk of inflammatory bowel diseases (IBDs), Crohn's disease (CD), and ulcerative colitis (UC) are needed for counseling of patients and could be used to target future ...prevention. We aimed to provide comprehensive population-based estimates of familial risk of IBD.
The study encompassed the entire Danish population during 1977-2011 (N=8,295,773; 200 million person-years). From national registries, we obtained information on diagnosis date of IBD (N=45,780) and family ties. Using Poisson regression, we estimated incidence rate ratios (IRRs) of IBD in relatives of IBD cases compared with individuals with relatives of the same type without IBD.
The risk of CD was significantly increased in first-degree (IRR, 7.77; 95% confidence interval (CI), 7.05-8.56), second-degree (IRR, 2.44; 95% CI, 2.01-2.96), and third-degree relatives (IRR, 1.88; 95% CI, 1.30-2.71) to patients with CD, and was less pronounced in relatives to UC cases. Likewise, the risk of UC was increased in first-degree (IRR, 4.08; 95% CI, 3.81-4.38), second-degree (IRR, 1.85; 95% CI, 1.60-2.13), and third-degree relatives (IRR, 1.51; 95% CI, 1.07-2.12) of UC cases, and less pronounced in relatives of CD cases. IRRs increased with two or more IBD-affected relatives and were modified by age, with the highest family-related IRR observed in early life.
The risk of IBD is significantly increased in first -, second-, and third-degree relatives of IBD-affected cases, with up to 12% of all IBD cases being family cases. The risk is particularly pronounced in young individuals.
Treatment possibilities have changed in inflammatory bowel disease (IBD). We assessed changes in medical treatment and surgery over time and impact of medications on risk of surgery in a ...population-based cohort.
48 967 individuals were diagnosed with IBD (Crohn's disease (CD), 13 185; ulcerative colitis (UC), 35 782) during 1979-2011. Cumulative probability of receiving 5-aminosalicylic acids (5-ASA), topical, oral corticosteroids, thiopurines, and tumour necrosis factor-α (TNF-α) blockers, and of first minor or major surgery according to period of diagnosis, was estimated. Medication use and risk of surgery was examined by Cox regression.
5-year cumulative probability of first major surgery decreased from 44.7% in cohort (1979-1986) to 19.6% in cohort (2003-2011) (p < 0.001) for CD, and from 11.7% in cohort (1979-1986) to 7.5% in cohort (2003-2011) (p < 0.001) for UC. Minor surgery risk decreased significantly in CD. From cohort (1995-2002) to cohort (2003-2011), a significant increase in use of thiopurines and TNF-α blockers was observed, paralleled by a significant decrease in use of 5-ASA and corticosteroids. Comparing use of azathioprine (or oral corticosteroids) to never-use, no convincing surgery-sparing effect was found. Comparing use in 3+ months of a given drug with use <3 months, only 3+ months use of oral corticosteroids reduced the risk of surgery in patients with disease duration of >1 year.
Parallel to an increasing use of thiopurines and TNF-α blockers in IBD over time, a persistent significant decrease in surgery rates was observed along with a significant decrease in use of 5-ASA and corticosteroids. However, no convincing surgery-sparing effect of newer medications was found.
Body mass index (BMI) has been related to risk of infections. The aim of this study was to assess the shape of the association between BMI and risk of infections and to evaluate whether such ...associations represent causality. We included 101,447 individuals from The Copenhagen General Population Study who had BMI measured. Outcome was hospital contacts related to infections. The shape of the association between BMI and risk of infections was examined using restricted cubic spline Cox regression. To evaluate causality, we used Mendelian randomization, an epidemiological method that counteracts confounding and reverse causality by using genetic variation as instrumental variables. We created a genetic risk score based on five genetic variants causing lifelong higher BMI and used this score in instrumental variable analysis. During median follow-up of 8.8 years, 10,263 hospital contacts related to infections were recorded. We found a U-shaped association between BMI and risk of any infection and pneumonia, and a linear association between BMI and risk of skin infection, urinary tract infection, and sepsis. In instrumental variable analyses, higher BMI was associated with increased risk of skin infection: odds ratio 1.12 (95% CI 1.03–1.22) for a genetically induced 1 unit increase in BMI. Observationally, low as well as high BMI was associated with increased risk of any infection and pneumonia, whereas only high BMI was associated with increased risk of skin infection, urinary tract infection, and sepsis. High BMI was causally associated with increased risk of skin infection.
Tumor necrosis factor-α(TNF-α)inhibitors are biological agents introduced in the late 1990s for the treatment of different immune-mediated diseases as inflammatory bowel disease,rheumatoid arthritis ...and psoriasis.The most commonly used TNF-αantagonists are infliximab,adalimumab,and certolizumab pegol,and though highly effective in lowering inflammation,the efficacy must be weighed against the potential for adverse events.The treatment-induced immunosuppression is suspected to increase the risk of infections,including the risk of reactivation of latent tuberculosis,as the TNF-αcytokine plays an important role in the immune function.In this topic highlight a short overview of the infection risk associated with TNF-αinhibiter therapy is outlined with a focus on the overall risk of serious infections,mycobacterial infection and latent viral infections.
Increased risks of lymphoma and skin cancer associated with thiopurine use among patients with inflammatory bowel disease have been shown, but data on the overall cancer risk are limited. We ...conducted a historical cohort study of 45,986 patients with inflammatory bowel disease (of whom, 5,197 (11%) used azathioprine) in Denmark from 1997 to 2008. We linked registry data on filled drug prescriptions, cancer diagnoses, and covariates and compared rates of overall incident cancer and cancer subgroups between users and nonusers of azathioprine, adjusting for propensity scores. During a median 7.9 (interquartile range: 3.5-12.0) person-years of follow-up, 2,596 incident cases of cancer were detected. Azathioprine use was associated with an increased risk of overall cancer (rate ratio = 1.41, 95% confidence interval: 1.15, 1.74), whereas former use of azathioprine (rate ratio = 1.02, 95% confidence interval: 0.83, 1.25) or increasing cumulative received doses (increase in rate ratio per 365 additional defined daily doses = 1.06, 95% confidence interval: 0.89, 1.27) were not. In subgroup analyses, azathioprine use was associated with increased risk of lymphoid tissue cancer (rate ratio = 2.40, 95% confidence interval: 1.13, 5.11) and urinary tract cancer (rate ratio = 2.84, 95% confidence interval: 1.24, 6.51). In conclusion, azathioprine use was associated with an increased risk of overall cancer in patients with inflammatory bowel disease, although these data cannot establish causality.
Extra-intestinal manifestations of inflammatory bowel disease (IBD) are relatively common, whereas the risk of extra-intestinal cancer (EIC) remains uncertain. The aim of this study was to obtain a ...reliable estimate of the risk of EIC in Crohn's disease (CD) and ulcerative colitis (UC) by performing a meta-analysis of population-based cohort studies.
A systematic literature review was performed using MEDLINE (1966-2009) and abstracts from recent international conferences. Eight population-based cohort studies comprising a total of 17,052 patients with IBD were available. Standardized incidence ratios (SIRs) of EICs were pooled in a meta-analysis approach using STATA software.
Overall, IBD patients were not at increased risk of EIC (SIR, 1.10; 95% confidence interval (CI) 0.96-1.27). However, site-specific analyses revealed that CD patients had an increased risk of cancer of the upper gastrointestinal tract (SIR 2.87, 95% CI 1.66-4.96), lung (SIR 1.82, 95% CI 1.18-2.81), urinary bladder (SIR 2.03, 95% CI 1.14-3.63), and skin (SIR 2.35, 95% CI 1.43-3.86). Patients with UC had a significantly increased risk of liver-biliary cancer (SIR 2.58, 95% CI 1.58-4.22) and leukemia (SIR 2.00, 95% CI 1.31-3.06) but a decreased risk of pulmonary cancer (SIR 0.39, 95% CI 0.20-0.74).
Although the overall risk of EIC was not significantly increased among patients with IBD, the risk of individual cancer types differed from that of the background population as well as between CD and UC patients. These findings may primarily be explained by smoking habits, extra-intestinal manifestations of IBD, and involvement of the upper gastrointestinal tract in CD.
Background High pre-pregnancy body mass index (BMI) and excessive gestational weight gain (GWG) are suggested to influence risk of asthma and atopic disease in offspring. Objective We examined the ...effect of BMI and GWG on risk of asthma, wheezing, atopic eczema (AE), and hay fever in children during the first 7 years of life. Methods This was a cohort study of 38,874 mother-child pairs from the Danish National Birth Cohort (enrollment 1996-2002) with information from the 16th week of pregnancy and at age 6 months, 18 months, and 7 years of the child. Odds ratios (ORs) with 95% CIs were calculated by logistic regression with adjustment for potential confounders. Results During the first 7 years of life, 10.4% of children developed doctor-diagnosed asthma, 25.8% AE, and 4.6% hay fever. Maternal BMI and to a lesser extent GWG were associated with doctor-diagnosed asthma ever. In particular, BMI ≥ 35 (adjusted OR, 1.87; 95% CI, 0.95-3.68) and GWG ≥ 25 kg (adjusted OR, 1.97; 95% CI, 1.38-2.83) were associated with current severe asthma at age 7 years. Maternal BMI was also associated with wheezing in offspring, with the strongest association observed between BMI ≥ 35 and late-onset wheezing (adjusted OR, 1.87; 95% CI, 1.28-2.73). Maternal BMI and GWG were not associated with AE or hay fever. Conclusions Maternal obesity during pregnancy was associated with increased risk of asthma and wheezing in offspring but not with AE and hay fever, suggesting that pathways may be nonallergic.
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