Antibiotic Exposure and Risk of New-Onset Inflammatory Bowel Disease: A Systematic Review and Dose-Response Meta-Analysis.

BACKGROUND & AIMS: The association between antibiotic exposure and inflammatory bowel disease (IBD) remains controversial, especially whether there is a dose-response relationship. We aimed to conduct a systematic review and meta-analysis to thoroughly evaluate the risk of new-onset IBD associated with antibiotic exposure. METHODS: Four databases were searched from their inception to September 30, 2023 for all relevant studies. The risk estimates were pooled together using random-effects models, and pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated, stratified by IBD subtype, age, exposure period, study type, and antibiotic classes. Dose-response relationship between the number of antibiotic prescriptions and IBD risk was assessed using generalized least squares regression analysis. RESULTS: Twenty-eight studies involving 153,027 patients with IBD were included. Antibiotic exposure was significantly associated with an increased risk of new-onset IBD for prescription-based studies (pooled OR, 1.41; 95% CI, 1.29-1.53) and for questionnaire-based studies (pooled OR, 1.35; 95% CI, 1.08-1.68). This association existed for both Crohn's disease and ulcerative colitis, as well as in children and adults for prescription-based studies. The majority of antibiotic classes were associated with an increased IBD risk, with metronidazole (OR, 1.70; 95% CI, 1.38-2.10) and quinolones (OR, 1.56; 95% CI, 1.37-1.77) having relatively higher risk estimates. A positive nonlinear dose-response association was observed between the number of antibiotic prescriptions and IBD risk. CONCLUSIONS: Antibiotic exposure was significantly associated with an increased risk of new-onset IBD, and a positive nonlinear dose-response relationship was observed. Antibiotic stewardship may be important for reducing IBD risk.

Helicobacter pylori infection is associated with reduced risk of Barrett's esophagus: a meta-analysis and systematic review.

BACKGROUND: Helicobacter pylori (Hp) is a class I carcinogen in gastric carcinogenesis, but its role in Barrett's esophagus (BE) is unknown. Therefore, we aimed to explore the possible relationship. METHODS: We reviewed observational studies published in English until October 2019. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for included studies. RESULTS: 46 studies from 1505 potential citations were eligible for inclusion. A significant inverse relationship with considerable heterogeneity was found between Hp (OR = 0.70; 95% CI, 0.51-0.96; P = 0.03) and BE, especially the CagA-positive Hp strain (OR = 0.28; 95% CI, 0.15-0.54; P = 0.0002). However, Hp infection prevalence was not significantly different between patients with BE and the gastroesophageal reflux disease (GERD) control (OR = 0.99; 95% CI, 0.82-1.19; P = 0.92). Hp was negatively correlated with long-segment BE (OR = 0.47; 95% CI, 0.25-0.90; P = 0.02) and associated with a reduced risk of dysplasia. However, Hp had no correlated with short-segment BE (OR = 1.11; 95% CI, 0.78-1.56; P = 0.57). In the present infected subgroup, Hp infection prevalence in BE was significantly lower than that in controls (OR = 0.69; 95% CI, 0.54-0.89; P = 0.005); however, this disappeared in the infection history subgroup (OR = 0.88; 95% CI, 0.43-1.78; P = 0.73). CONCLUSIONS: Hp, especially the CagA-positive Hp strain, and BE are inversely related with considerable heterogeneity, which is likely mediated by a decrease in GERD prevalence, although this is not observed in the absence of current Hp infection.

The efficacy and safety of acid suppressants for gastrointestinal bleeding prophylaxis in cardiac care unit patients.

BACKGROUND AND AIM: Concerns regarding adverse events associated with proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) for gastrointestinal bleeding (GIB) prophylaxis in the intensive care unit have increased in recent years. Few studies have focused on acid suppressant use in the cardiac care unit (CCU) setting exclusively. We performed a cohort study to determine the efficacy and safety of acid suppressants for GIB prophylaxis in CCU patients. METHODS: This retrospective cohort study included adults who were admitted directly to the CCU for more than 2 days from January 1, 2014, to April 30, 2019. The Crusade score was calculated to evaluate the risk of GIB. The primary outcomes were clinically important gastrointestinal bleeding (CIGIB), hospital-acquired pneumonia (HAP), and in-hospital mortality. RESULTS: Of the 3318 patients enrolled, 2284 (68.8%) patients received PPIs, 515 (15.5%) received H2RAs, and 519 (15.7%) received no acid suppressants. After adjusting for potential confounders, utilization of PPIs (2.69, 95% confidence interval [0.62-11.73]) and H2RAs (1.41, 95% confidence interval [0.19-10.36]) were not associated with a lower risk of CIGIB than the control. Sensitivity analyses revealed that PPI use was an independent risk factor for in-hospital mortality in patients over 75 years old, with an adjusted odds ratio of 4.08 (1.14-14.63). PPIs increased the risk of HAP in patients over 75 years old and in those with heart failure, with adjusted odds ratios of 2.38 (1.06-5.34) and 2.88 (1.34-7.28), respectively. CONCLUSIONS: Proton pump inhibitors and H2RAs for GIB prophylaxis in CCU patients were not associated with a lower risk of CIGIB than the controls. PPI therapy is associated with increased risks of HAP and in-hospital mortality in patients over 75 years old. PPIs may increase the risk of HAP in patients with heart failure.

Association between short-term exposure to fine particulate pollution and outpatient visits for ulcerative colitis in Beijing, China: A time-series study.

Environmental factors play an important role in the development of ulcerative colitis (UC). However, only few studies have examined the effects of air pollution on UC occurrence. We conducted a time-series analysis to explore the association between short-term exposure to fine particulate matter (PM2.5) and outpatient visits for UC in Beijing, China. In total, 84,000 outpatient visits for UC were retrieved from the Beijing Medical Claim Data for Employees between January 1, 2010 and June 30, 2012. Measurements of daily PM2.5 concentrations were obtained from the United States Embassy air-monitoring station. A generalized additive model with quasi-Poisson link was applied to examine the association between PM2.5 concentrations and outpatient visits for UC stratified by sex, age, and season. We found that short-term exposure to PM2.5 was significantly associated with increased daily outpatient visits for UC at lag 0 day. A 10 µg/m3 increase in PM2.5 concentration at lag 0 day corresponded to a 0.32% increase in outpatient visits for UC (95% confidence interval (CI), 0.05-0.58%; P = 0.019). There was a clear concentration-response association between daily outpatient visits for UC and PM2.5 concentrations. The PM2.5 effects were significant across all sex and season subgroups, without evidence of effect modification by sex (P = 0.942) or season (P = 0.399). The association was positive in patients younger than 65 years old but negative in those 65 years old or older, although the difference was not significant (P = 0.883). In conclusion, our study demonstrated that short-term exposure to ambient PM2.5 was significantly associated with an increased risk of daily outpatient visits for UC, especially in younger people. Additional studies are warranted to confirm our findings.

Impact of short-term proton pump inhibitors vs. histamine-2 receptor antagonists on gut microbiota in patients with acute coronary syndrome: A multicenter randomized trial.

BACKGROUND: Several randomized controlled studies have suggested that the prophylactic use of proton pump inhibitors (PPIs) in intensive care unit (ICU) patients could not reduce the incidence of gastrointestinal bleeding (GIB) and may increase adverse events such as intestinal infection and pneumonia. Gut microbiota may play a critical role in the process. PPIs has been widely prescribed for GIB prophylaxis in patients with acute coronary syndrome (ACS). This study aimed to determine the short-term effects of PPI and histamine-2 receptor antagonist (H2RA) treatment on gut microbiota of ACS patients. METHODS: The study was designed as a single-blind, multicenter, three-parallel-arm, randomized controlled trial conducted at three centers in Beijing, China. We enrolled ACS patients at low-to-medium risk of GIB and randomized (2:2:1) them to either PPI (n = 40), H2RA (n = 31), or control group (n = 21). The primary outcomes were the alterations in gut microbiota after 7 days of acid suppressant therapy. Stool samples were collected at baseline and 7 days and analyzed by 16S rRNA gene sequencing. RESULTS: There were no significant changes in the diversity of gut microbiota after the short-term use of acid suppressants, but the abundance of Fusobacterium significantly increased and that of Bifidobacterium significantly decreased, especially in PPI users. In addition, the abundance of some pathogenic bacteria, including Enterococcus and Desulfovibrio, was significantly elevated in the PPI users. The fecal microbiota of the PPI users included more arachidonic acid metabolism than that of control group. CONCLUSIONS: PPIs may increase the risk of infection by adversely altering gut microbiota and elevating arachidonic acid metabolism, which may produce multiple proinflammatory mediators. For ACS patients at low-to-medium risk of GIB, sufficient caution should be paid when acid-suppressant drugs are prescribed, especially PPIs. REGISTRATION: www.chictr.org.cn/ (ChiCTR2000029552).

Alterations of Gut Microbiota in Patients With Irritable Bowel Syndrome Based on 16S rRNA-Targeted Sequencing: A Systematic Review.

INTRODUCTION: Alterations of gut microbiota have been thought to be associated with irritable bowel syndrome (IBS). Many studies have reported significant alterations of gut microbiota in patients with IBS based on 16S ribosomal RNA-targeted sequencing. However, results from these studies are inconsistent or even contradictory. We performed a systematic review to explore the alterations of gut microbiota in patients with IBS compared with healthy controls (HCs). METHODS: The databases PubMed, Cochrane Library, Web of Science, and Embase were searched for studies published until February 28, 2018, for case-control studies detecting gut microbiota in patients with IBS. Methodological quality was assessed using the Newcastle-Ottawa Scale. The α-diversity and alterations of gut microbiota in patients with IBS compared with HCs were analyzed. RESULTS: Sixteen articles involving 777 patients with IBS and 461 HCs were included. Quality assessment scores of the studies ranged from 5 to 7. For most studies, patients with IBS had a lower α-diversity than HCs in both fecal and mucosal samples. Relatively consistent changes in fecal microbiota for patients with IBS included increased Firmicutes, decreased Bacteroidetes, and increased Firmicutes:Bacteroidetes ratio at the phylum level, as well as increased Clostridia and Clostridiales, decreased Bacteroidia and Bacteroidales at lower taxonomic levels. Results for mucosal microbiota were inconsistent. CONCLUSIONS: Alterations of gut microbiota exist in patients with IBS and have significant association with the development of IBS. Further studies are needed to draw conclusions about gut microbiota changes in patients with IBS. TRANSLATIONAL IMPACT: This knowledge might improve the understanding of microbial signatures in patients with IBS and would guide future therapeutic strategies.

Prevalence of sleep disorder in irritable bowel syndrome: A systematic review with meta-analysis.

Background/Aims: We conducted this meta-analysis to evaluate the prevalence of sleep disorder in irritable bowel syndrome (IBS) patients and study the association between IBS and sleep disorder. Materials and Methods: A systematic search was conducted by searching PubMed, Embase, and Cochrane library databases using the following search terms: "functional gastrointestinal disorders," "Sleep disturbance," "Sleep disorder," "insomnia," "Dysomnias," "irritable bowel syndrome," and "IBS." Studies evaluating the association between IBS and sleep disorder were identified. Data analysis was conducted using meta-analysis software Comprehensive Meta-Analysis (CMA) 2.0. Heterogeneity across studies was evaluated by χ2and I2statistics. Publication bias was evaluated by funnel plot, Begg's test, and Egger's test. Sensitivity analysis was also performed by removing each single study separately. Results: The bibliographical search yielded a total of 2866 studies. Finally, 36 studies including 63620 participants were identified. The prevalence of sleep disorder in IBS was 37.6% (95% CI: 31.4% to 44.3%) based on this meta-analysis. The pooled odds ratio was 2.618 (95% CI: 2.052% to 3.341). Publication bias was not determined. Regarding the sensitivity analysis, the outcome was stable regardless of which study was removed. Conclusions: The prevalence of sleep disorder was higher in IBS compared to healthy controls and may be associated with the pathogenesis of IBS. The prevalence of sleep disorder in IBS may differ according to different areas, age, gender, occupation, and IBS diagnostic criteria. Further studies are needed to investigate any possible causal relationship between sleep disorder and IBS.