Efficacy and Safety of Probiotics in Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis
- 作者列表："Bing Li","Li Liang","Huijie Deng","Jinmin Guo","He Shu","Li Zhang
BackgroundIrritable bowel syndrome is a functional gastrointestinal disease. Evidence has suggested that probiotics may benefit IBS symptoms. However, clinical trials remain conflicting.AimsTo implement a systematic review and meta-analysis of clinical trials regarding the efficacy and safety of probiotics for IBS patients.MethodsWe searched for relevant trials in Medline(1966 to Jan 2019), Embase(1974 to Jan 2019), the Cochrane Central Register of Controlled Trials(up to Jan 2019), the ClinicalTrials.gov trials register(up to Jan 2019), and Chinese Biomedical Literature Database(1978 to Jan 2019). Risk ratio (RR) and a 95% confidence interval (CI) were calculated for dichotomous outcomes. Standardized mean difference (SMD) and 95% CI were calculated for continuous outcomes.ResultsA total of 59 studies, including 6,761 patients, were obtained. The RR of the improvement or response with probiotics versus placebo was 1.52 (95% CI 1.32–1.76), with significant heterogeneity (I2 = 71%, P < 0.001). The SMD of Probiotics in improving global IBS symptoms vs. Placebo was -1.8(95% CI -0.30 to -0.06), with significant heterogeneity (I2 = 65%, P < 0.001). It was impossible to draw a determinate conclusion. However, there were differences in subgroup analyses of probiotics type, dose, treatment duration, and geographic position. Probiotics seem to be safe by the analysis of adverse events(RR = 1.07; 95% CI 0.92–1.24; I2 = 0, P = 0.83).ConclusionProbiotics are effective and safe for IBS patients. Single probiotics with a higher dose (daily dose of probiotics ≥1010) and shorter duration (< 8 weeks) seem to be a better choice, but it still needs more trials to prove it.
背景肠综合征是一种功能性胃肠病。有证据表明益生菌可能有益于 IBS 症状。然而，临床试验仍然相互矛盾。目的实施一项关于益生菌对 IBS 患者疗效和安全性的临床试验的系统综述和荟萃分析。方法检索 Medline(1966 ~ 2019年1月) 、 Embase(1974 ~ 2019年1月) 、 Cochrane 中心对照试验登记册 (截至 2019年1月) 、 clinicalTrials.gov 试验注册 (截至 2019年1月),和中国生物医学文献数据库 (1978 ~ 2019年1月)。计算二分类结局的风险比 (RR) 和 95% 置信区间 (CI)。计算连续结局的标准化平均差 (SMD) 和 95% CI。结果共获得 59 项研究，包括 6,761 例患者。益生菌与安慰剂相比改善或反应的 RR 为 1.52 (95% CI 1.32-1.76)，具有显著异质性 (I2 = 71%，P <0.001)。益生菌改善整体 IBS 症状 vs.安慰剂的 SMD 为-1.8(95% CI -0.30 ~-0.06)，异质性显著 (I2 = 65%，P <0.001)。不可能得出一个确定的结论。然而，益生菌类型、剂量、治疗持续时间和地理位置的亚组分析存在差异。通过不良事件分析，益生菌似乎是安全的 (RR = 1.07; 95% CI 0.92-1.24; I2 = 0，P = 0.83)。结论益生菌对 IBS 患者有效且安全。剂量较高 (益生菌日剂量 ≥ 1010) 和持续时间较短 (< 8 周) 的单一益生菌似乎是更好的选择，但仍需要更多的试验来证明。
METHODS::Chronic diseases, including inflammatory bowel disease (IBD) urgently need new biomarkers as a significant proportion of patients, do not respond to current medications. Inflammation is a common factor in these diseases and microbial sensing in the intestinal tract is critical to initiate the inflammation. We have identified ELMO1 (Engulfment and Cell Motility Protein-1) as a microbial sensor in epithelial and phagocytic cells that turns on inflammatory signals. Using a stem-cell-based "gut-in-a-dish" coculture model, we studied the interactions between microbes, epithelium and monocytes in the context of IBD. To mimic the in-vivo cell physiology, enteroid-derived monolayers (EDMs) were generated from the organoids isolated from WT and ELMO1-/- mice and colonic biopsies of IBD patients. The EDMs were infected with the IBD-associated microbes to monitor the inflammatory responses. ELMO1-depleted EDMs displayed a significant reduction in bacterial internalization, a decrease in pro-inflammatory cytokine productions and monocyte recruitment. The expression of ELMO1 is elevated in the colonic epithelium and in the inflammatory infiltrates within the lamina propria of IBD patients where the higher expression is positively correlated with the elevated expression of pro-inflammatory cytokines, MCP-1 and TNF-α. MCP-1 is released from the epithelium and recruits monocytes to the site of inflammation. Once recruited, monocytes require ELMO1 to engulf the bacteria and propagate a robust TNF-α storm. These findings highlight that the dysregulated epithelial ELMO1→MCP-1 axis can serve as an early biomarker in the diagnostics of IBD and other inflammatory disorders.
METHODS:BACKGROUND:Peripheral blood eosinophilia (PBE) is a biomarker of an aggressive multiyear natural history in adults with inflammatory bowel diseases (IBDs). Additionally, PBE at diagnosis is associated with higher disease activity in pediatric-onset IBD. We sought to determine if PBE can function as a biomarker of long-term disease severity in pediatric-onset IBD patients who are followed into adulthood. METHODS:We analyzed a consented, prospective, natural history IBD registry at an adult tertiary center from 2009 to 2018. Prevalence of PBE was evaluated in both pediatric- and adult-onset IBD patients. Demographics, clinical characteristics, and health care utilization data were compared in patients with and without PBE. RESULTS:Among 2800 adult IBD patients, 23.4% had pediatric-onset disease. PBE was found in 34% of the pediatric-onset patients compared with 26.8% of the adult-onset IBD patients (P < 0.001). In the pediatric-onset IBD cohort, PBE was associated with higher rates of allergies (P < 0.0001), but not of asthma, allergic rhinitis, or primary sclerosing cholangitis. In the adult IBD patients with pediatric-onset disease, PBE was associated with higher rates of C-reactive protein elevation (P < 0.0001), erythrocyte sedimentation rate elevation (P < 0.0001), higher health care utilization, and higher average health care charges per year (P < 0.00001). CONCLUSIONS:Peripheral blood eosinophilia was more prevalent in adult IBD patients with pediatric-onset compared with adult-onset disease. Among all IBD patients with long-term follow-up, PBE defined a subgroup with more severe illness. These data suggest that PBE may be a biomarker for a high-risk subgroup with high cost trajectory and long-term severity in pediatric-onset IBD that persists into adulthood.
METHODS::Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders with a complex pathogenesis, affecting people of all ages. They are characterized by alternating phases of clinical relapse and remission, depending on the fine balance between immune cells and the gut microbiota. The cross talk between cells of the immune system and the gut microbiota can result in either tolerance or inflammation, according to multifactorial triggers, ranging from environmental factors to genetic susceptibility. Glucocorticoid (GC) administration remains the first-line treatment for IBDs, although long-term use is limited by development of serious adverse effects. Recently, new alternative pharmacological therapies have been developed, although these are not always effective in IBD patients. There is a constant demand for effective new drug targets to guarantee total remission and improve the quality of life for IBD patients. The glucocorticoid-induced leucine zipper (GILZ) has been implicated as a promising candidate for this purpose, in view of its powerful anti-inflammatory effects that mimic those of GCs while avoiding their unwanted adverse reactions. Here we present and discuss the latest findings about the involvement of GILZ in IBDs.