Antibiotic therapy in inflammatory bowel disease: a systematic review and meta-analysis

The etiology of inflammatory bowel disease (IBD) is unknown but may relate to an unidentified bacterial pathogen or an immunological reaction to gut microbiota. Antibiotics have therefore been proposed as a therapy for Crohn's disease (CD) and ulcerative colitis (UC) to induce remission in active disease to prevent relapse. Current data are conflicting and we therefore conducted a systematic review of randomized controlled trials (RCTs) evaluating antibiotics in IBD. Only parallel group RCTs were considered eligible. Studies with adult patients receiving any dose of therapy for at least 7 days and up to 16 weeks for active disease, or at least 6 months of follow-up for preventing relapse in quiescent disease were analyzed. We included any antibiotics alone or in combination using predefined definitions of remission and relapse. Two reviewers independently assessed eligibility and extracted data. The primary outcome was remission or relapse using an intention-to-treat methodology. The data were summarized using relative risk (RR) and pooled using a random effects model. For active CD, there were 10 RCTs involving 1,160 patients. There was a statistically significant effect of antibiotics being superior to placebo (RR of active CD not in remission=0.85; 95% confidence interval (CI)=0.73-0.99, P=0.03). There was moderate heterogeneity between results (I(2)=48%) and a diverse number of antibiotics were tested (anti-tuberculosis therapy, macrolides, fluroquinolones, 5-nitroimidazoles, and rifaximin) either alone or in combination. Rifamycin derivatives either alone or in combination with other antibiotics appeared to have a significant effect at inducing remission in active CD. In perianal CD fistula there were three trials evaluating 123 patients using either ciprofloxacin or metronidazole. There was a statistically significant effect in reducing fistula drainage (RR=0.8; 95% CI=0.66-0.98) with no heterogeneity (I(2)=0%) and an number needed to treat 5 (95% CI=3-20). For quiescent CD, there were 3 RCTs involving 186 patients treated with different antibiotics combinations (all including antimycobacterials) vs. placebo. There was a statistically significant effect in favor of antibiotics vs. placebo (RR of relapse=0.62; 95% CI=0.46-0.84), with no heterogeneity (I(2)=0%). In active UC, there were 9 RCTs with 662 patients and there was a statistically significant benefit for antibiotics inducing remission (RR of UC not in remission=0.64; 95% CI=0.43-0.96). There was moderate heterogeneity (I(2)=69%) and antibiotics used were all different single or combination drugs. Antibiotic therapy may induce remission in active CD and UC, although the diverse number of antibiotics tested means the data are difficult to interpret. This systematic review is a mandate for further trials of antibiotic therapy in IBD.     

Factor V Leiden and prothrombin gene mutation in inflammatory bowel disease in Mediterranean area

Background. Thromboembolism has been reported to be associated with inflammatory bowel disease.Aim. To evaluate the association of factor V Leiden and prothrombin gene mutation with inflammatory bowel disease in a population of patients with thromboembolic events and inflammatory bowel disease and in a control population of patients with inflammatory bowel disease without thromboembolic events.Patients and methods. A series of 18 patients with inflammatory bowel disease and a history of arterial or venous thrombosis and 45 patients with inflammatory bowel disease without thromboembolic events were evaluated for the presence of factor V Leiden and prothrombin gene mutation. Frequency of gene mutation was compared with its occurrence in 100 healthy controls.Results. One patient with inflammatory bowel disease without thromboembolic events was heterozygous for factor V Leiden mutation. whereas no patient with a thromboembolic event had factor V Leiden mutation. No patients (either cases or controls) had prothrombin gene mutation. In the healthy population the frequency of factor V Leiden and prothrombin mutation was 5% and 2%, respectively.Conclusions. Data emerging from the present study do not support any role of factor V Leiden and prothrombin gene mutation as the cause of thromboembolism in inflammatory bowel disease.     

Factor V Leiden and prothrombin gene mutation in inflammatory bowel disease in a Mediterranean area.

BACKGROUND: Thromboembolism has been reported to be associated with inflammatory bowel disease. AIM: To evaluate the association of factor V Leiden and prothrombin gene mutation with inflammatory bowel disease in a population of patients with thromboembolic events and inflammatory bowel disease and in a control population of patients with inflammatory bowel disease without thromboembolic events. PATIENTS AND METHODS: A series of 18 patients with inflammatory bowel disease and a history of arterial or venous thrombosis and 45 patients with inflammatory bowel disease without thromboembolic events were evaluated for the presence of factor V Leiden and prothrombin gene mutation. Frequency of gene mutation was compared with its occurrence in 100 healthy controls. RESULTS: One patient with inflammatory bowel disease without thromboembolic events was heterozygous for factor V Leiden mutation. whereas no patient with a thromboembolic event had factor V Leiden mutation. No patients (either cases or controls) had prothrombin gene mutation. In the healthy population the frequency of factor V Leiden and prothrombin mutation was 5% and 2%, respectively. CONCLUSIONS: Data emerging from the present study do not support any role of factor V Leiden and prothrombin gene mutation as the cause of thromboembolism in inflammatory bowel disease.     

Factor V Leiden: a clinical review

Factor V Leiden is the most prevalent genetic thrombophilia in people of European descent. Since its discovery, much clinical information has been gathered regarding the distribution and prevalence of the genetic mutation, the mechanism of thrombophilia, and its association with clinical thromboembolic events. Although its association with venous thromboembolism is clear, the role of Factor V Leiden in other disease states is not clear. A review of the literature regarding the mechanism of hypercoagulability, genetic versus functional diagnostic tests, screening issues, relationship to arterial thromboses, pregnancy and pregnancy complications, and treatment are discussed.     

Colonic lesion characterization in inflammatory bowel disease: A systematic review and meta-analysis

AIM To perform a systematic review and meta-analysis for the diagnostic accuracy of in vivo lesion characterization in colonic inflammatory bowel disease(IBD), using optical imaging techniques, including virtual chromoendoscopy(VCE), dye-based chromoendoscopy(DBC), magnification endoscopy and confocal laser endomicroscopy(CLE). METHODS We searched Medline, Embase and the Cochrane library. We performed a bivariate meta-analysis to calculate the pooled estimate sensitivities, specificities, positive and negative likelihood ratios(+LHR,-LHR), diagnostic odds ratios(DOR), and area under the SROC curve(AUSROC) for each technology group. A subgroup analysis was performed to investigate differences in real-time nonmagnified Kudo pit patterns(with VCE and DBC) and real-time CLE.RESULTS We included 22 studies [1491 patients; 4674 polyps, of which 539(11.5%) were neoplastic]. Real-time CLE had a pooled sensitivity of 91%(95%CI: 66%-98%), specificity of 97%(95%CI: 94%-98%), and an AUSROC of 0.98(95%CI: 0.97-0.99). Magnification endoscopy had a pooled sensitivity of 90%(95%CI: 77%-96%)and specificity of 87%(95%CI: 81%-91%). VCE had a pooled sensitivity of 86%(95%CI: 62%-95%) and specificity of 87%(95%CI: 72%-95%). DBC had a pooled sensitivity of 67%(95%CI: 44%-84%) and specificity of 86%(95%CI: 72%-94%). CONCLUSION Real-time CLE is a highly accurate technology for differentiating neoplastic from non-neoplastic lesions in patients with colonic IBD. However, most CLE studies were performed by single expert users within tertiary centres, potentially confounding these results.     

Renal manifestations in inflammatory bowel disease: a systematic review

Journal of Gastroenterology - As extra-intestinal manifestations (EIMs) are frequent in inflammatory bowel disease (IBD) and affect morbidity and sometimes even mortality, vigilance in the...     

Serological antibodies in inflammatory bowel disease: a systematic review

The diagnosis of inflammatory bowel disease (IBD) is traditionally based on a combination of clinical, endoscopic, histological, and radiological criteria. However, further testing is needed in cases of diagnostic uncertainty and in predicting disease course. This systematic review focuses on the potential for 10 serological antibodies to fill these roles: pANCA, ASCA, anti-OmpC, anti-CBir1, anti-I2, ALCA, ACCA, AMCA, anti-L, and anti-C. We discuss their prevalence in IBD and health; their role in disease diagnosis and risk stratification; their stability over time; their presence in unaffected relatives; their association with genetic variants; and differences across ethnic groups. Serological antibodies have some role in primary diagnosis and in differentiating between Crohn's disease and ulcerative colitis. In indeterminate colitis, preoperative measurement of serological antibodies can help to predict the likelihood of complications among patients undergoing pouch surgery. The combined presence and magnitude of a large panel of antibodies appear to be of value in predicting disease progression. There is currently insufficient evidence to recommend the use of antibody testing to predict responses to treatment or surgery in patients with IBD.     

Heart rate variability and inflammatory bowel disease in humans: A systematic review and meta-analysis

The autonomic nervous system (ANS) maintains homeostasis in the gastrointestinal tract, including immunity, inflammation and motility, through the brain-gut axis. To date, the associations between ANS function and inflammatory bowel disease (IBD) have been controversial and inconclusive in human studies. PubMed, Cochrane Library, and Embase were searched through February 2020 for articles reporting these association between heart rate variability (HRV), an indirect measure of ANS activity, and IBD. The standardized mean differences and 95% confidence intervals (CIs) were calculated. Ten eligible studies involving 273 ulcerative colitis patients, 167 Crohn''s disease patients and 208 healthy controls were included. The values of the total power (SMD = −0.83, 95% CI = −1.44, −0.21), high frequency (SMD = −0.79, 95% CI = −1.20, −0.38), RR interval (SMD = −0.66, 95% CI = −1.04, −0.27), standard deviation of the RR intervals (SMD = −1.00, 95% CI = −1.73, −0.27), percentage of RR intervals with a greater than 50-millisecond variation (SMD = −0.82, 95% CI = −1.33, −0.30) and the square root of the mean squared differences in successive RR intervals (SMD = −0.71, 95% CI = −1.15, −0.26) of the IBD patients were lower than those of the healthy controls, and moderate to large effect sizes were observed in all HRV indices, except for low frequency (SMD = −0.41, 95% CI = 0.95, 0.13). IBD was strongly associated with an overall decrease in HRV, indicating substantially decreased ANS activity. Furthermore, the parasympathetic nerve displayed a stronger inverse association with ANS activity than the sympathetic nerve, indicating ANS dysfunction in patients with IBD.     

Correlation between antibiotic use in childhood and subsequent inflammatory bowel disease: a systematic review and meta-analysis

Abstract

Background: Antibiotic use leads to a cascade of inflammatory reaction in the gastrointestinal tract due to its association with a temporary disruption of human microbiome.

Objectives: To explore the undetermined correlation between antibiotic use in childhood and subsequent inflammatory bowel disease (IBD).

Methods: PUBMED, EMBASE and Cochrane Central Register of Controlled Trials were searched to identify related articles. We extracted and pooled the (adjusted) odds ratio (OR) and (adjusted) risk ratio (RR).

Results: This systematic review and meta-analysis included 11 studies. The pooled OR of all 11 studies was 1.5 (95% confidence interval (CI): 1.22–1.85). The pooled ORs of the subsequent Crohn’s disease and ulcerative colitis after antibiotic use in childhood were 1.59 (95% CI: 1.06–2.4) and 1.22 (95% CI: 0.82–1.8). The sensitivity analysis showed no change. The meta-regression showed there was not statistical significance for the publication year, research area and research methods. Egger’s test showed publication bias in the IBD studies (p = .006 < .05) but no publication bias for the CD (p = .275>.05) and UC studies (p = .537>.05).

Conclusions: There was a positive association between antibiotic use in childhood and the subsequently risk of Crohn’s disease in non-European countries in the west during 2010–2013. Children in the United States taking antibiotics will have a higher risk of subsequently IBD than Europe, Asia and Australia.

Registration number: CRD42019147648 (PROSPERO)     

Fecal microbiota transplantation as therapy for inflammatory bowel disease: A systematic review and meta-analysis

Background and aimsFecal microbiota transplantation (FMT) has gained interest as a novel treatment option for inflammatory bowel diseases (IBD). While publications describing FMT as therapy for IBD have more than doubled since 2012, research that investigates FMT treatment efficacy has been scarce. We conducted a systematic review and meta-analysis to evaluate the efficacy of FMT as treatment for patients with IBD.MethodsA systematic literature search was performed through May 2014. Inclusion criteria required FMT as the primary therapeutic agent. Clinical remission (CR) and/or mucosal healing were defined as primary outcomes. Studies were excluded if they did not report clinical outcomes or included patients with infections.ResultsEighteen studies (9 cohort studies, 8 case studies and 1 randomized controlled trial) were included. 122 patients were described (79 ulcerative colitis (UC); 39 Crohn's disease (CD); 4 IBD unclassified). Overall, 45% (54/119) of patients achieved CR during follow-up. Among the cohort studies, the pooled proportion of patients that achieved CR was 36.2% (95% CI 17.4%–60.4%), with a moderate risk of heterogeneity (Cochran's Q, P = 0.011; I² = 37%). Subgroup analyses demonstrated a pooled estimate of clinical remission of 22% (95% CI 10.4%–40.8%) for UC (P = 0.37; I² = 0%) and 60.5% (95% CI 28.4%–85.6%) for CD (P = 0.05; I² = 37%). Six studies performed microbiota analysis.ConclusionsThis analysis suggests that FMT is a safe, but variably efficacious treatment for IBD. More randomized controlled trials are needed and should investigate frequency of FMT administration, donor selection and standardization of microbiome analysis.     

Factor V Leiden, prothrombin G20210A and MTHFR gene mutations in inflammatory bowel disease.

BACKGROUND/AIMS: Thromboembolic events are more common in patients with inflammatory bowel disease than in the normal population; however, the reason for the increased prevalence is not clear. The aim of this study was to evaluate the prevalence of factor V Leiden, prothrombin G20210A and methylene tetrahydrofolate reductase (MTHFR) gene mutations in IBD patients followed in our outpatient clinic. METHODS: Thirty-four patients with ulcerative colitis and 28 patients with Crohn's disease and 80 healthy controls were included in the study. No patient had a history of previous thromboembolism. Factor V Leiden, prothrombin G20210A and MTHFR gene mutations were studied. RESULTS: Heterozygote factor V Leiden mutation was found in five (6.25%) control patients and in two (3.2%) IBD patients. Heterozygote MTHFR mutation was obtained in seven (11.3%) IBD patients and in five (6.25%) controls. Heterozygote prothrombin G20210A mutation was found in two (2.5%) and homozygote MTHFR mutation in one (1.25%) control patient. There was no statistical difference between the IBD group and healthy controls. CONCLUSIONS: Genetic mutations that could increase the thrombosis risk were not found to be different in IBD versus the normal population in our study.