Interaction of obesity and inflammatory bowel disease

Inflammatory bowel disease (IBD) is a chronic inflammatory condition of unknown etiology that is thought to result from a combination of genetic, immunologic and environmental factors. The incidence of IBD has been increasing in recent decades, especially in developing and developed nations, and this is hypothesized to be in part related to the change in dietary and lifestyle factors associated with modernization. The prevalence of obesity has risen in parallel with the rise in IBD, suggesting a possible shared environmental link between these two conditions. Studies have shown that obesity impacts disease development and response to therapy in patients with IBD and other autoimmune conditions. The observation that adipose tissue produces pro-inflammatory adipokines provides a potential mechanism for the observed epidemiologic links between obesity and IBD, and this has developed into an active area of investigative inquiry. Additionally, emerging evidence highlights a role for the intestinal microbiota in the development of both obesity and IBD, representing another potential mechanistic connection between the two conditions. In this review we discuss the epidemiology of obesity and IBD, possible pathophysiologic links, and the clinical impact of obesity on IBD disease course and implications for management.     

炎症性肠病危险因素的流行病学调查研究

目的通过病例调查，筛选IBD的危险因素。方法采用问卷方式，对72例确诊IBD患者及72例配对的健康个体调查，对结果进行COX回归分析，筛选出IBD的致病危险因素。结果COX回归分析提示紧张度、牛奶和油炸食品在IBD致病因素中具有统计学意义。结论紧张度、牛奶和油炸食品可能是IBD的致病危险因素。     

流行病学调查探讨炎症性肠病的危险因素

目的通过问卷式大样本病例调查，探讨炎症性肠病（IBD）致病的可能危险因素。方法采用问卷法，对140例确诊IBD患者及140例配对的健康个体调查，问卷包括遗传、吸烟的年限、牛奶摄入量、油炸食品摄入量和酒精摄入量等共14项内容，收回问卷后对结果进行COX回归分析，筛选出IBD的具有统计学意义的致病危险因素。结果COX回归分析提示牛奶摄入量、油炸食品摄入量、吸烟的年限在IBD致病因素中具有统计学意义。结论牛奶摄入、油炸食品摄入、吸烟可能是IBD的致病危险因素。     

Prevalence and factors associated with vitamin C deficiency in inflammatory bowel disease

BACKGROUNDPatients with inflammatory bowel disease (IBD) are prone to several nutritional deficiencies. However, data are lacking on vitamin C deficiency in Crohn’s disease (CD) and ulcerative colitis (UC) patients, as well as the impact of clinical, biomarker and endoscopic disease severity on the development of vitamin C deficiency.AIMTo determine proportions and factors associated with vitamin C deficiency in CD and UC patients.METHODSIn this retrospective study, we obtained clinical, laboratory and endoscopic data from CD and UC patients presenting to the IBD clinic at a single tertiary care center from 2014 to 2019. All patients had an available plasma vitamin C level. Of 353 subjects who met initial search criteria using a cohort discovery tool, 301 ultimately met criteria for inclusion in the study. The primary aim described vitamin C deficiency (≤ 11.4 μmol/L) rates in IBD. Secondary analyses compared proportions with deficiency between active and inactive IBD. Multivariate logistic regression analysis evaluated factors associated with deficiency.RESULTSOf 301 IBD patients, 21.6% had deficiency, including 24.4% of CD patients and 16.0% of UC patients. Patients with elevated C-reactive protein (CRP) (39.1% vs 16.9%, P < 0.001) and fecal calprotectin (50.0% vs 20.0%, P = 0.009) had significantly higher proportions of deficiency compared to those without. Penetrating disease (P = 0.03), obesity (P = 0.02) and current biologic use (P = 0.006) were also associated with deficiency on univariate analysis. On multivariate analysis, the objective inflammatory marker utilized for analysis (elevated CRP) was the only factor associated with deficiency (odds ratio = 3.1, 95% confidence interval: 1.5-6.6, P = 0.003). There was no difference in the presence of clinical symptoms of scurvy in those with vitamin C deficiency and those without.CONCLUSIONVitamin C deficiency was common in IBD. Patients with elevated inflammatory markers and penetrating disease had higher rates of vitamin C deficiency.     

Nested case-control study on risk factors for opportunistic infections in patients with inflammatory bowel disease

BACKGROUND When opportunistic infections occur, patients with inflammatory bowel disease(IBD) commonly display a significantly increased rate of morbidity and mortality.With increasing use of immunosuppressive agents and biological agents,opportunistic infections are becoming a hot topic in the perspective of drug safety in IBD patients. Despite the well-established role of opportunistic infections in the prognosis of IBD patients, there are few epidemiological data investigating the incidence of opportunis-tic infections in IBD patients in China. Besides, the risk factors for opportunistic infection in Chinese IBD patients remain unclear.AIM To predict the incidence of opportunistic infections related to IBD in China, and explore the risk factors for opportunistic infections.METHODS A single-center, prospective study of IBD patients was conducted. The patients were followed for up to 12 mo to calculate the incidence of infections. For each infected IBD patient, two non-infected IBD patients were selected as controls. A conditional logistic regression analysis was used to assess associations between putative risk factors and opportunistic infections, which are represented as odds ratios(OR) and 95% confidence intervals(CIs).RESULTS Seventy(28.11%) out of 249 IBD patients developed opportunistic infections.Clostridium difficile infections and respiratory syncytial virus infections were found in 24 and 16 patients, respectively. In a univariate analysis, factors such as the severity of IBD, use of an immunosuppressant or immunosuppressants, high levels of fecal calprotectin, and C-reactive protein or erythrocyte sedimentation rate were individually related to a significantly increased risk of opportunistic infection. Multivariate analysis indicated that the use of any immunosuppressant yielded an OR of 3.247(95%CI: 1.128-9.341), whereas the use of any two immunosuppressants yielded an OR of 6.457(95%CI: 1.726-24.152) for opportunistic infection. Interestingly, when immunosuppressants were used in combination with infliximab(IFX) or 5-aminosalicylic acid, a significantly increased risk of opportunistic infection was also observed. The relative risk of opportunistic infection was greatest in IBD patients with severe disease activity(OR = 9.090; 95%CI: 1.532-53.941, relative to the remission stage). However, the use of IFX alone did not increase the risk of opportunistic infection.CONCLUSION Factors such as severe IBD, elevated levels of fecal calprotectin, and the use of immunosuppressive medications, especially when used in combination, are major risk factors for opportunistic infections in IBD patients. The use of IFX alone does not increase the risk of opportunistic infection.     

Risk factors associated with inflammatory bowel disease: A multicenter case-control study in Brazil

BACKGROUND The etiology of inflammatory bowel disease(IBD) is unknown, but it is believed to be multifactorial. The hygiene hypothesis proposes that better hygiene conditions would lead to less infectious disease during childhood and favor the development of immune-mediated diseases.AIM To test the hygiene hypothesis in IBD by assessing the environmental risk factors associated with IBD development in different regions of Brazil with diverse socioeconomic development indices.METHODS A multicenter case-control study was carried out with 548 Crohn's disease(CD) and 492 ulcerative colitis(UC) outpatients and 416 healthy controls, from six IBD centers within different Brazilian states at diverse socioeconomic development stages. A semi-structured questionnaire with 87 socioeconomic and environmental questions was applied. Logistic regression model was created to assess the odds ratio(OR) with P value and 95% confidence intervals(CI).RESULTS Predictive variables for both diseases(CD and UC) were women [odd ratios(OR) = 1.31; OR = 1.69], low monthly family income(OR = 1.78; OR = 1.57), lower number of cohabitants(OR = 1.70; OR = 1.60), absence of vaccination(OR = 3.11; OR = 2.51), previous history of bowel infections(OR = 1.78; OR = 1.49), and family history of IBD(OR = 5.26; OR = 3.33). Associated risk factors for CD were age(18-39 years)(OR = 1.73), higher educational level(OR = 2.22), absence of infectious childhood diseases(OR = 1.99). The UC predictive variables were living in an urban area(OR = 1.62), inadequate living conditions(OR = 1.48) and former smokers(OR = 3.36). Appendectomy was a risk factor for CD(OR = 1.58) with inverse association with UC(OR = 4.79). Consumption of treated and untreated water was associated with risk of CD(OR = 1.38) and UC(OR = 1.53), respectively.CONCLUSION This is the first examining environmental exposures as risk factors for inflammatory bowel disease in Brazil. Most of the variables associated with disease risk support the role of the hygiene hypothesis in IBD development.     

Antibiotics and probiotics in treatment of inflammatory bowel disease

Many experimental and clinical observations suggest that intestinal microflora plays a potential role in the pathogenesis of inflammatory bowel disease (IBD). Manipulation of the luminal content using antibiotics or probiotics represents a potentially effective therapeutic option. The available studies do not support the use of antibiotics in ulcerative colitis (UC). Antibiotics are effective in treating septic complications of Crohn's disease (CD) but their use as a primary therapy is more controversial, although this approach is frequently and successfully adopted in clinical practice. There is evidence that probiotic therapy may be effective in the prevention and treatment of mild to moderate UC. In contrast, a lack of successful study data at present precludes the widespread use of probiotics in the treatment of CD. Both antibiotics and probiotics appear to play a beneficial role in the treatment and prevention of pouchitis and further trials are warranted to fully quantify their clinical efficacy.     

Anemia at the time of diagnosis of inflammatory bowel disease: Prevalence and associated factors in adolescent and adult patients

BackgroundThe prevalence, characteristic and determinants of anemia, at the time of inflammatory bowel disease (IBD) diagnosis have yet to be fully elucidated.MethodsRetrospective cross-sectional study. Analytical data and disease characteristics obtained upon diagnosis of 1278 IBD patients [Crohn’s disease/ulcerative colitis (CD/UC): 718/560] were collected.ResultsAnemia was present in 41.2% of patients at diagnosis (47% and 33.8% of CD and UC patients, respectively; p < 0.001), being severe in 5.5%. Iron deficiency anemia represented 69.6% of cases, with no differences between CD and UC. Female sex was the strongest risk factor for anemia in both CD and UC (OR 7.11; 95%CI 4.18–12.10 and 6.55; 95%CI 3.39–12.63, respectively), followed by elevated (≥2 mg/dL) C-reactive protein (OR 4.08; 95%CI 2.39–6.97 and 4.58; 95%CI 2.26–9.27, respectively). Current smoking was a risk factor for anemia in CD (OR 2.23; 95%CI 1.24–4.02), but a protective one in UC (OR 0.36; 95%CI 0.14–0.92). A penetrating CD behavior increased the risk of anemia (OR 3.34; 95%CI 1.36–8.21); in UC, anemia increased with disease extension (E2 + E3) (OR 1.80; 95%CI 1.13–2.86).ConclusionsFemale sex and disease activity are major determinants of anemia at IBD diagnosis. Anemia is associated with disease behavior in CD and with disease extension in UC.     

Significant risk and associated factors of active tuberculosis infection in Korean patients with inflammatory bowel disease using anti-TNF agents

AIM:To evaluate the incidence and risk factors of Korean tuberculosis(TB) infection in patients with inflammatory bowel disease(IBD) undergoing anti-TNF treatment.METHODS:The data of IBD patients treated with anti-TNFs in 13 tertiary referral hospitals located in the southeastern region of Korea were collected retrospectively.They failed to show response or were intolerant to conventional treatments,including steroids or immunomodulators.Screening measures for latent TB infection(LTBI)and the incidence and risk factors ofactive TB infection after treatment with anti-TNFs were identified.RESULTS:Overall,376 IBD patients treated with antiTNF agents were recruited(male 255,mean age of anti-TNF therapy 32.5±13.0 years);277 had Crohn’s disease,99 had ulcerative colitis,294 used infliximab,and 82 used adalimumab.Before anti-TNF treatment,screening tests for LTBI including an interferon gamma release assay or a tuberculin skin test were performed in 82.2%of patients.Thirty patients(8%)had LTBI.Sixteen cases of active TB infection including one TB-related mortality occurred during 801 personyears(PY)follow-up(1997.4 cases per 100000 PY)after anti-TNF treatment.LTBI(OR=5.76,95%CI:1.57-21.20,P=0.008)and WBC count5000 mm3(OR=4.5,95%CI:1.51-13.44,P=0.007)during follow-up were identified as independently associated risk factors.CONCLUSION:Anti-TNFs significantly increase the risk of TB infection in Korean patients with IBD.The considerable burden of TB and marked immunosuppression might be attributed to this risk.     

Prevalence and risk factors of Clostridium difficile infection in patients hospitalized for flare of inflammatory bowel disease: A retrospective assessment

BackgroundRecent studies have identified a high frequency of Clostridium difficile infections in patients with active inflammatory bowel disease.AimsTo retrospectively assess the determinants and results of Clostridium difficile testing upon the admission of patients hospitalized with active inflammatory bowel disease in a tertiary care centre and to determine the predicting factors of Clostridium difficile infections.MethodsWe reviewed all admissions from January 2008 and December 2010 for inflammatory bowel disease flare-ups. A toxigenic culture and a stool cytotoxicity assay were performed for all patients tested for Clostridium difficile.ResultsOut of 813 consecutive stays, Clostridium difficile diagnostic assays have been performed in 59% of inpatients. The independent predictive factors for the testing were IBD (ulcerative colitis: OR 2.0, 95% CI 1.5–2.9; p < 0.0001) and colonic involvement at admission (OR 2.2, 95% CI 1.5–3.1, p < 0.0001). Clostridium difficile infection was present in 7.0% of the inpatients who underwent testing. In a multivariate analysis, the only independent predictor was the intake of nonsteroidal anti-inflammatory drugs within the two months before admission (OR 3.8, 95% CI 1.2–12.3; p = 0.02).ConclusionsClostridium difficile infection is frequently associated with active inflammatory bowel disease. Our study suggests that a recent intake of nonsteroidal anti-inflammatory drugs is a risk factor for inflammatory bowel disease -associated Clostridium difficile infection.     

Genetic factors associated with the development of inflammatory bowel disease

Crohn＇s disease （CD） and ulcerative colitis （UC） are complex polygenic disorders, characterized by several genes together with environmental factors contributing to the development of inflammatory bowel disease （IBD）. Recent advances in research on genetic susceptibility have allowed the identification of diverse genes at different levels： （1） Innate immunity; （2） Antigen presentation molecules; （3） Epithelial integrity; （4） Drug transporter; （5） Cell adhesion. The application of genetic testing into clinical practice is close and all genetic markers may have several clinical implications： prediction of disease phenotype, molecular classification, prevention of complications, and prognosis.     

Clostridium difficile infection and inflammatory bowel disease: understanding the evolving relationship

Clostridium difficile(C.difficile)infection(CDI)is the leading identifiable cause of antibiotic-associated diarrhea.While there is an alarming trend of increasing incidence and severity of CDI in the United States and Europe,superimposed CDI in patients with inflammatory bowel disease(IBD)has drawn considerable attention in the gastrointestinal community.The majority of IBD patients appear to contract CDI as outpatients.C.difficile affects disease course of IBD in several ways,including triggering disease flares,sustaining activity,and in some cases,acting as an"innocent"bystander.Despite its wide spectrum of presentations,CDI has been reported to be associated with a longer duration of hospitalization and a higher mortality in IBD patients.IBD patients with restorative proctocolectomy or with diverting ileostomy are not immune to CDI of the small bowel or ileal pouch.Whether immunomodulator or corticosteroid therapy for IBD should be continued in patients with superimposed CDI is controversial.It appears that more adverse outcomes was observed among patients treated by a combination of immunomodulators and antibiotics than those treated by antibiotics alone.The use of biologic agents does not appear to increase the risk of acquisition of CDI.For CDI in the setting of underlying IBD,vancomycin appears to be more efficacious than metronidazole.Randomized controlled trials are required to clearly define the appropriate management for CDI in patients with IBD.     

炎性肠病患者发生非酒精性脂肪性肝病的危险因素

目的探讨炎症肠病(inflammatory bowel disease,IBD)患者非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)患病情况及相关危险因素。方法以2017年1月至2019年10月新疆军区总医院收治的409例IBD患者为研究对象,应用腹部超声筛查NAFLD,根据是否合并NAFLD分为NAFLD组(131例)和对照组(278例),比较两组患者年龄、性别、体重指数(body mass index,BMI)、腹围、病程及并发症(高血压、糖尿病、吸烟)、天门冬氨酸氨基转移酶(aspartate aminotransferase,AST)、丙氨酸氨基转移酶(alanine aminotransferase,ALT)、γ-谷氨酰转移酶(gamma-glutamyltransferase,GGT)、白蛋白、糖化血红蛋白(glycosylated hemoglobin,HbA1c)、低密度脂蛋白胆固醇(low density lipoprotein cholesterol,LDL-C)、血肌酐、估算肾小球滤过率(estimated glomerular filtration rate,eGFR)和C-反应蛋白(C-reactive protein,CRP)等的差异。采用Logistic回归分析IBD患者发生NAFLD的独立危险因素。结果IBD患者NAFLD的患病率为32.03%(131/409)。NAFLD组患者年龄[(50.24±12.83)岁vs(38.74±10.91)岁]、BMI[(28.24±4.90)kg/m2 vs(23.52±3.73)kg/m2]、腹围[(93.10±11.52)cm vs(85.52±10.06)cm]、病程[(8.52±1.84)年vs(5.84±1.28)年]、高血压比例[20.61%(27/131)vs 4.68%(13/278)]、糖尿病比例[9.92%(13/131)vs 1.80%(5/278)]、吸烟比例[50.38%(66/131)vs 38.13%(106/278)]、GGT[(26.57±8.19)U/L vs(18.46±4.36)U/L]和HbA1c[(6.65±2.17)%vs(3.64±1.05)%]水平均显著高于对照组,差异有统计学意义(P均<0.05)。多因素Logistic回归分析表明年龄(OR=1.33,95%CI:1.15~1.82,P=0.018)、BMI(OR=1.80,95%CI:1.25~3.27,P=0.002)、病程(OR=2.60,95%CI:1.10~3.26,P=0.010)和糖尿病(OR=1.77,95%CI:1.23~4.79,P=0.006)是IBD患者发生NAFLD的独立危险因素。结论IBD患者NAFLD的患病率高,年龄、BMI、病程和糖尿病均是IBD患者发生NAFLD的独立危险因素,可通过促进健康生活方式进行代谢干预,以减少NAFLD的发生。     

Risk of cardiovascular disease in inflammatory bowel disease

Abundant scientific evidence supporting an association between inflammatory bowel disease(IBD) and venous thromboembolic events, caused by an IBD related hypercoagulability, is acknowledged and thromboprophylactic treatment strategies are now implemented in the management of IBD patients. In contrary, the risk of arterial thromboembolic disease, as ischemic heart disease, cerebrovascular events, and mesenteric ischemia in patients with IBD remains uncertain and the magnitude of a potentially increased risk is continuously debated, with ambiguous risk estimates among studies. The evident role of inflammation in the pathogenesis of atherosclerosis forms the basis of a biological plausible link; the chronic systemic inflammation in IBD patients increases the risk of atherosclerosis and thereby the risk of thrombotic events. Further, studies have shown that the burden of traditional risk factors for atherosclerosis, such as obesity, diabetes mellitus, and dyslipidemia is lower in IBD populations, thus further strengthen the role of non-traditional risk factors, as chronic inflammation in the linking of the two disease entities. Likewise, mortality from cardiovascular disease in IBD remains questioned. The aim of the current review is to give an up-date on the existing evidence of the possible association between IBD and cardiovascular disease and to discuss traditional and non-traditional risk factors.     

Venous thrombosis and prothrombotic factors in inflammatory bowel disease

Patients with inflammatory bowel disease(IBD)may have an increased risk of venous thrombosis(VTE).PubMed,ISI Web of Knowledge and Scopus were searched to identify studies investigating the risk of VTE and the prevalence of acquired and genetic VTE risk factors and prothrombotic abnormalities in IBD.Overall,IBD patients have a two-to fourfold increased risk of VTE compared with healthy controls,with an overall incidence rate of 1%-8%.The majority of studies did not show significant differences in the risk of VTE between Crohn’s disease and ulcerative colitis.Several acquired factors are responsible for the increased risk of VTEin IBD:inflammatory activity,hospitalisation,surgery,pregnancy,disease phenotype(e.g.,fistulising disease,colonic involvement and extensive involvement)and drug therapy(mainly steroids).There is also convincing evidence from basic science and from clinical and epidemiological studies that IBD is associated with several prothrombotic abnormalities,including initiation of the coagulation system,downregulation of natural anticoagulant mechanisms,impairment of fibrinolysis,increased platelet count and reactivity and dysfunction of the endothelium.Classical genetic alterations are not generally found more often in IBD patients than in nonIBD patients,suggesting that genetics does not explain the greater risk of VTE in these patients.IBD VTE may have clinical specificities,namely an earlier first episode of VTE in life,high recurrence rate,decreased efficacy of some drugs in preventing further episodes and poor prognosis.Clinicians should be aware of these risks,and adequate prophylactic actions should be taken in patients who have disease activity,are hospitalised,are submitted to surgery or are undergoing treatment.     

Obesity and novel management of inflammatory bowel disease

Obesity is prevalent within the inflammatory bowel disease(IBD) population,particularly in newly developed countries.Several epidemiological studies have suggested that 15%-40% of IBD patients are obese,and there is a potential role of obesity in the pathogenesis of IBD.The dysfunction of mesenteric fat worsens the inflammatory course of Crohn’s disease and may induce formation of strictures or fistulas.Furthermore,obesity may affect the disease course or treatment response of IBD.Given the incr...     

Rifaximin in the treatment of inflammatory bowel disease

The gut microbiota plays a role in promoting and maintaining inflammation in inflammatory bowel diseases (IBD),hence the rationale for the use of antibiotics in the treatment of those disorders.Antibiotics,however, may induce untoward effects,especially during long- term therapy.Rifaximin polymer is an antibacterial agent that is virtually unabsorbed after oral adminis- tration and is devoid of systemic side effects.Rifaximin has provided promising results in inducing remission of Crohn's disease(up to 69%i...     

Nutritional status as a predictor of hospitalization in inflammatory bowel disease:A review

BACKGROUND Inflammatory bowel disease(IBD) presents an inflammatory picture that in the long run can lead to complications and consequently more hospitalizations compared to other diseases.AIM To evaluate the influence of nutritional status on the occurrence of IBD-related hospitalization.METHODS This integrative review was conducted in the online databases PubMed and MEDLINE, using the terms "obesity" and "malnutrition" accompanied by"hospitalization", each combined with "Crohn's disease" or "ulcerative colitis".Only studies conducted with humans, adults, and published in English or Spanish were selected, and those that were not directly associated with nutritional status and hospitalization were excluded from this review. The Preferred Reporting Items for Systematic Reviews and Meta-Analyzes guide was used as the basis for selection of studies.RESULTS Of the 80 studies identified, only five met the proposal of this review. None evaluated the association of good nutritional status with the risk of hospitalization. Malnutrition had a strong correlation with the risk of hospitalization related to IBD, and there was disagreement among three studies regarding the association of obesity and hospitalization rates.CONCLUSION Few studies have evaluated nutritional status as a predictor of IBD-related hospitalization. The presence of malnutrition appears to be associated with hospitalization in these patients, but further studies are needed to elucidate the issue.