Meta-analysis: Lactobacillus GG for treating acute diarrhoea in children

AIM: To review evidence for the effectiveness of Lactobacillus GG (LGG) in treating acute infectious diarrhoea in children. METHODS: The following electronic databases were searched through August 2006 for studies relevant to acute infectious diarrhoea and LGG: MEDLINE, EMBASE, CINAHL and The Cochrane Library; additional references were obtained from reviewed articles. Only randomized-controlled trials (RCTs) were included. RESULTS: Eight RCTs (988 participants) met the inclusion criteria. Compared with controls, LGG had no effect on the total stool volume (two RCTs, n = 303). However, LGG was associated with a significant reduction in diarrhoea duration (seven RCTs, 876 infants, weighted mean difference, WMD -1.1 days (95% confidence interval, CI -1.9 to -0.3), particularly of rotavirus etiology (WMD -2.1 days, 95% CI -3.6 to -0.6), risk of diarrhoea >7 days (one RCT, n = 287, relative risk 0.25, 95% CI 0.09-0.75) and duration of hospitalization (three RCTs, n = 535, WMD -0.58, 95% CI -0.8 to -0.4; significance was lost in the random effect model). There was no reduction in the number of stools at any time interval. CONCLUSIONS: The use of LGG is associated with moderate clinical benefits in the treatment of acute diarrhoea in children. These findings should be interpreted with caution due to the important methodological limitations and heterogeneity of most of the studies.     

Meta-analysis: Lactobacillus rhamnosus GG for abdominal pain-related functional gastrointestinal disorders in childhood

Background A lack of reliable treatments for abdominal pain‐related functional gastrointestinal disorders prompts interest in new therapies. Aim To evaluate systematically the effect of Lactobacillus rhamnosus GG (LGG) for treating abdominal pain‐related functional gastrointestinal disorders in children. Methods MEDLINE, EMBASE, CINAHL, the Cochrane Library, trial registries and proceedings of major meetings were searched for randomised controlled trials (RCTs) evaluating LGG supplementation in children with abdominal pain‐related functional gastrointestinal disorders based on the Rome II or Rome III criteria. Risk of bias was assessed for generation of the allocation sequence, allocation concealment, blinding and follow‐up. Results Compared with placebo, LGG supplementation was associated with a significantly higher rate of treatment responders (defined as no pain or a decrease in pain intensity) in the overall population with abdominal pain‐related functional gastrointestinal disorders (three RCTs, n = 290; risk ratio, RR 1.31, 95% CI 1.08–1.59, number needed to treat, NNT 7, 95% CI 4–22) and in the irritable bowel syndrome (IBS) subgroup (three RCTs, n = 167; RR 1.70, 95% CI 1.27–2.27, NNT 4, 95% CI 3–8). However, no difference was found in the rate of treatment responders between children with functional abdominal pain or functional dyspepsia who received placebo or LGG. The intensity of pain was significantly reduced in the overall study population and in the IBS subgroup. The frequency of pain was significantly reduced in the IBS subgroup only. Conclusion The use of Lactobacillus rhamnosus GG moderately increases treatment success in children with abdominal pain‐related functional gastrointestinal disorders, particularly among children with IBS.     

Probiotic Lactobacillus rhamnosus GG enhances gastric ulcer healing in rats

Probiotics are widely used as functional foods which have been advocated for the maintenance of gastrointestinal microflora equilibrium and treatment of gastrointestinal disorders. However, studying the role of probiotics in peptic ulcer disease is limited. The aim of the present study is to investigate the effect of a probiotic strain Lactobacillus rhamnosus GG on gastric ulcer and to elucidate the mechanisms involved. Gastric kissing ulcers were induced in rats by acetic acid (60% v/v). L. rhamnosus GG was given intragastrically at 10(8) cfu/day or 10(9) cfu/day for three consecutive days after ulcer induction. L. rhamnosus GG successfully colonized in the gastric mucosa especially at the ulcer margin. It also significantly and dose-dependently reduced gastric ulcer area. Cell apoptosis to cell proliferation ratio was strongly decreased and accompanied by significant up-regulation of ornithine decarboxylase (ODC) and B-cell lymphoma 2 (Bcl-2) protein expression at the ulcer margin. Angiogenesis was also significantly stimulated together with the induction of vascular endothelial growth factor (VEGF) expression. Furthermore, L. rhamnosus GG up-regulated the phosphorylation level of epidermal growth factor receptor (EGF receptor) without altering the total EGF receptor expression. These findings suggested that L. rhamnosus GG enhanced gastric ulcer healing via the attenuation of cell apoptosis to cell proliferation ratio and increase in angiogenesis. Regulators of these processes such as ODC, Bcl-2, VEGF and EGF receptor are likely to be involved in the healing action of L. rhamnosus GG for gastric ulcer.     

Clinical trial: effectiveness of Lactobacillus rhamnosus (strains E/N, Oxy and Pen) in the prevention of antibiotic-associated diarrhoea in children

Background  Convincing evidence that probiotic administration can lower the risk of antibiotic-associated diarrhoea is limited to certain micro-organisms.
Aim  To determine the efficacy of administration of Lactobacillus rhamnosus (strains E/N , Oxy and Pen ) for the prevention of antibiotic-associated diarrhoea in children.
Methods  Children (aged 3 months to 14 years) with common infections were enrolled in a double-blind, randomized, placebo-controlled trial in which they received standard antibiotic treatment plus 2 × 10¹⁰ colony forming units of a probiotic ( n  = 120) or a placebo ( n  = 120), administered orally twice daily throughout antibiotic treatment. Analyses were by intention to treat.
Results  Any diarrhoea (≥3 loose or watery stools/day for ≥48 h occurring during or up to 2 weeks after the antibiotic therapy) occurred in nine (7.5%) patients in the probiotic group and in 20 (17%) patients in the placebo group (relative risk, RR 0.45, 95% confidence interval, CI 0.2–0.9). Three (2.5%) children in the probiotic group developed AAD (diarrhoea caused by Clostridium difficile or otherwise unexplained diarrhoea) compared to nine (7.5%) in the placebo group (RR 0.33, 95% CI 0.1–1.06). No adverse events were observed.
Conclusion  Administration of L. rhamnosus (strains E/N , Oxy and Pen ) to children receiving antibiotics reduced the risk of any diarrhoea, as defined in this study.     

Effect of Lactobacillus rhamnosus GG on ileal pouch inflammation and microbial flora

BACKGROUND: Preliminary trials of probiotics in preventing recurrent chronic pouchitis have been encouraging. AIM: To investigate the efficacy of Lactobacillus GG supplementation as primary therapy for ileal pouch inflammation, and its effect on the microbial flora. METHODS: Twenty patients, with a previous history of pouchitis and endoscopic inflammation, were recruited for a prospective, randomized, double-blind, placebo-controlled trial of Lactobacillus GG supplementation (10 LGG, 10 placebo) in two gelatine capsules [(0.5-1) x 10(10) colony-forming units/capsule] b.d. for 3 months. Quantitative bacterial culture of fresh faecal samples and biopsies taken from the pouch and afferent limb was performed before and after supplementation. RESULTS: Lactobacillus GG supplementation changed the pouch intestinal flora by increasing the ratio of total faecal lactobacilli to total faecal anaerobes (P = 0.03) and enhancing the frequency of lactobacilli-positive cultures in the pouch and afferent limb mucosal biopsy samples. However, only 40% of patients were colonized with Lactobacillus GG. No differences were observed between the groups with regard to the mean pouchitis disease activity index or the total anaerobes or aerobes of faecal or tissue biopsy samples. CONCLUSIONS: A single-strain probiotic bacterium supplement of Lactobacillus GG changed the pouch intestinal bacterial flora, but was ineffective as primary therapy for a clinical or endoscopic response. More clinical trials are needed to evaluate the right placement and dosage of probiotics within a treatment regimen for pouchitis.     

乳酸菌素治疗小儿急性腹泻的Meta分析

目的:评价乳酸菌素治疗小儿急性腹泻的作用。方法:通过计算机检索CENTRAL(theCochrane central register of controlledtrials)、Medline、EMBASE、中国期刊全文数据库(CNKI)、中国生物医学文献数据库系统(CBM)、万方数据库等,收集国内外发表的涉及乳酸菌素治疗小儿急性腹泻的随机对照研究(RCT)。研究人群为急性腹泻患儿;干预措施为口服乳酸菌素;对照组为安慰剂;结局指标为腹泻持续时间,并以标准化均数差(sandard mean differece,SMD)及相应的95%置信区间作为效应指标对结局进行比较。Q统计量的I2检验来检测各研究间的统计学异质性。双侧P<0.05认为各研究间存在明显的异质性。采用Egger检验对发表偏倚进行量化检测。应用统计软件Stata11.0进行数据分析。结果:纳入分析的文章有7篇,共945例患者,其中乳酸菌素组479例,对照组466例。Meta分析结果显示接受乳酸菌素治疗的患儿腹泻持续时间平均缩短1.24 d[SMD=-1.24,95%CI=(-2.21,-0.28),Z=2.54,P=0.01]。结论:乳酸菌素治疗小儿急性腹泻有一定临床疗效。     

Meta-analysis: Saccharomyces boulardii for treating acute diarrhoea in children

BACKGROUND: Saccharomyces boulardii is a non-pathogenic probiotic yeast considered useful against enteropathogens. AIM: To assess the effectiveness of S. boulardii in treating acute infectious diarrhoea in children. METHODS: The following electronic databases were searched through August 2006 for studies relevant to acute infectious diarrhoea and S. boulardii: MEDLINE, EMBASE, CINAHL and The Cochrane Library; additional references were obtained from reviewed articles. Only randomized-controlled trials were included. RESULTS: Five randomized-controlled trials (619 participants) met the inclusion criteria. Combined data from four randomized-controlled trials showed that S. boulardii significantly reduced the duration of diarrhoea compared with control. The pooled weighted mean difference was -1.1 days (95% CI: -1.3 to -0.8) with a fixed model and remained significant in a random effect model. Saccharomyces boulardii significantly reduced the risk of diarrhoea on days 3, 6 and 7. Also the risk of diarrhoea lasting >7 days was significantly reduced in the S. boulardii group vs. control group (1 RCT, n = 88, RR 0.25, 95% CI: 0.08-0.83; NNT 5, 95% CI: 3-20). CONCLUSIONS: There exists a moderate clinical benefit of S. boulardii therapy in otherwise healthy infants and children with acute gastroenteritis, mainly a shorter duration of diarrhoea. However, these results should be interpreted with caution due to methodological limitations of the included studies.     

Meta-analysis: zinc supplementation for acute gastroenteritis in children

Background  Uncertainty exists regarding the use of zinc in the treatment of acute gastroenteritis in children living in Europe, where zinc deficiency is rare.
Aim  To review evidence for the effectiveness of zinc in treating acute gastroenteritis in children, with special emphasis on data from developed countries.
Methods  MEDLINE, EMBASE, and the Cochrane Library were searched through November 2007 for randomized controlled trials (RCTs) relevant to acute gastroenteritis in children younger than 5 years of age and zinc; additional references were obtained from the reviewed articles.
Results  Eighteen RCTs (11 180 participants, mainly from developing countries) met the inclusion criteria. Use of zinc was associated with a significant reduction in diarrhoea duration (13 RCTs, 5643 infants, weighted mean difference −0.69 day, 95% CI −0.97 to −0.40) and the risk of diarrhoea lasting longer than 7 days [eight RCTs, n  = 5769, relative risk (RR) 0.71, 95% CI 0.53–0.96]. No significant reduction in stool volume was observed for those receiving zinc compared with placebo (three RCTs, n  = 606, standardized mean difference, −0.38, 95% CI −1.04 to 0.27). Combined data from five RCTs ( n  = 3156) showed that zinc significantly increased the chance of vomiting compared to the control agent (RR 1.2, 95% CI 1.05–1.4).
Conclusions  These data confirm that zinc supplementation can be useful for treating acute gastroenteritis in children, particularly those from developing countries. However, the role of zinc supplements in treating children with acute gastroenteritis in developed countries needs further evaluation.     

Meta-analysis: non-pathogenic yeast Saccharomyces boulardii in the prevention of antibiotic-associated diarrhoea

BACKGROUND: Antibiotic-associated diarrhoea occurs in up to 30% of patients who receive antibiotics but can be prevented with probiotics. AIM: To systematically evaluate the effectiveness of Saccharomyces boulardii in preventing antibiotic-associated diarrhoea in children and adults. METHODS: Using medical subject headings and free-language terms, the following electronic databases were searched for studies relevant to antibiotic-associated diarrhoea and S. boulardii: MEDLINE, EMBASE, CINAHL and The Cochrane Library. Additional sources were obtained from references in reviewed articles. Only randomized-controlled trials were considered for study inclusion. RESULTS: Of 16 potentially relevant clinical trials identified, five randomized-controlled trials (1076 participants) met the inclusion criteria for this systematic review. Treatment with S. boulardii compared with placebo reduced the risk of antibiotic-associated diarrhoea from 17.2% to 6.7% (RR: 0.43; 95% CI: 0.23-0.78; random effect model). The number needed to treat to prevent one case of antibiotic-associated diarrhoea was 10 (95% CI: 7-16). No side-effects were reported. CONCLUSIONS: A meta-analysis of data from five randomized-controlled trials showed that S. boulardii is moderately effective in preventing antibiotic-associated diarrhoea in children and adults treated with antibiotics for any reason (mainly respiratory tract infections). For every 10 patients receiving daily S. boulardii with antibiotics, one fewer will develop antibiotic-associated diarrhoea.     

鼠李糖乳杆菌片对小鼠肠道菌群失调性腹泻的治疗作用

目的：考察微生态制剂鼠李糖乳杆菌片对肠道菌群失调性腹泻的治疗作用。方法：将小鼠分为正常组、模型组、阳性对照组和高、中、低3个剂量的鼠李糖乳杆菌片实验组。除正常组外,其余各组采用抗生素（氨苄青霉素）联合致病菌（鼠伤寒沙门菌）诱发肠道菌群失调性腹泻。实验组分别灌胃不同剂量（1．0×10^8、1．0×10^7和1．0×10^6CFU·kg^-1）的鼠李糖乳杆菌片,阳性对照组灌胃使用丽珠肠乐胶囊0．3g,连续给药7天,通过对小鼠腹泻程度的观察和肠道菌群分析,考察该活菌制剂的干预作用。结果：用药7天后,鼠李糖乳杆菌片高、中剂量组小鼠的腹泻程度显著改善,量效关系明显。与模型组相比,该制剂高、中剂量组小鼠盲肠内容物中肠杆菌、肠球菌数量显著降低,且下降的乳杆菌、双歧杆菌的数量也恢复正常。结论：鼠李糖乳杆菌片可有效改善抗生素及致病菌诱发的小鼠肠道菌群失调及腹泻症状。     

Meta-analysis: Smectite in the treatment of acute infectious diarrhoea in children

BACKGROUND: Although not currently recommended, dioctahedral smectite (smectite) is commonly used to treat acute infectious diarrhoea in many countries. AIM: To evaluate systematically the effectiveness of smectite in treating acute infectious diarrhoea in children. METHODS: Using medical subject headings and free-language terms, the following electronic databases were searched for studies relevant to acute infectious diarrhoea and smectite: MEDLINE, EMBASE, CINAHL and The Cochrane Library; additional references were obtained from reviewed articles. Only randomized-controlled trials were included. RESULTS: Nine randomized-controlled trials (1238 participants) met the inclusion criteria. Combined data from six randomized-controlled trials showed that smectite significantly reduced the duration of diarrhoea compared with placebo. The pooled weighted mean difference was (-22.7 h, 95% CI: -24.8 to -20.6) with a fixed model and remained significant in a random effect model (-24.4 h, 95% CI: -29.8 to -19.1). The chance of cure on intervention day 3 was significantly increased in the smectite vs. the control group (RR 1.64, 95% CI: 1.36-1.98; number needed to treat 4, 95% CI: 3-5). Adverse effects were similar in both groups. CONCLUSIONS: Smectite may be a useful adjunct to rehydration therapy in treating acute paediatric gastroenteritis. However, the results of this meta-analysis should be interpreted with caution as most of the included studies had important limitations. Cost-effectiveness analyses should be undertaken before routine pharmacological therapy with smectite is recommended.     

A randomized double-blind placebo-controlled trial of Lactobacillus GG for abdominal pain disorders in children

BACKGROUND: Functional abdominal pain disorders (FAPD) are common in school-aged children; however, there is no reliable treatment. AIM: To determine the efficacy of Lactobacillus rhamnosus GG (LGG) for treating FAPD in children. METHODS: A total of 104 children who fulfilled the Rome II criteria for functional dyspepsia (FD), or irritable bowel syndrome (IBS), or functional abdominal pain (FAP) were enrolled in a double-blind, randomized controlled trial in which they received LGG (n = 52), or placebo (n = 52) for 4 weeks. RESULTS: For the overall study population, those in the LGG group were more likely to have treatment success (no pain) than those in the placebo group (25% vs. 9.6%, relative benefit (RB) 2.6, 95% confidence interval (CI): 1.05-6.6, number needed to treat (NNT) 7, 95% CI: 4-123). For children with IBS (n = 37), those in the LGG group were more likely to have treatment success than those in the placebo group (33% vs. 5%, RB 6.3, 95% CI: 1.2-38, NNT 4, 95% CI: 2-36) and reduced frequency of pain (P = 0.02), but not pain severity (P = 0.10). For the FD group (n = 20) and FAP group (n = 47), no differences were found. CONCLUSION: The LGG appears to moderately increase treatment success, particularly among children with IBS.     

Treatment of acute infectious diarrhoea in infants and children with a mixture of three Lactobacillus rhamnosus strains--a randomized, double-blind, placebo-controlled trial

BACKGROUND: Multiple studies document that probiotics are effective in treating infectious diarrhoea in children. Lactobacillus rhamnosus GG is the most extensively studied but effectiveness of other strains has been poorly examined. AIM: To determine whether L. rhamnosus strains (573L/1; 573L/2; 573L/3) (Lakcid L, Biomed, Lublin, Poland) would be effective in shortening infectious diarrhoea. METHODS: In a randomized, double-blind, placebo-controlled trial, 87 children (age range: 2 months to 6 years) with infectious diarrhoea were administered Lakcid L at a dose 1.2 x 10(10) CFU or placebo, twice daily, for 5 days. Primary outcome measure was the duration of diarrhoea. Secondary measures were duration of parenteral rehydration, adverse events, and gastrointestinal tract colonization by administered strains. RESULTS: In an intention to treat analysis of 87 children, the mean duration of diarrhoea in the treated group: 84 +/- 56 h; placebo: 96 +/- 72 h (P = 0.36). In rotavirus infection: 76 +/- 35 h vs. 115 +/- 67 h (P = 0.03), respectively. Duration of parenteral rehydration: 15 +/- 14 h vs. 38 +/- 33 h (P = 0.006). Gut colonization by administered strains was 80% and 41% at five and 14 days, respectively. No adverse events were noted. CONCLUSIONS: Administration of L. rhamnosus strains shortens the duration of rotaviral diarrhoea in children but not of diarrhoea of any aetiology. Intervention shortens the time of intravenous rehydration.