Archive for category Diarrhea/AAD
Lomax A, Calder P. Probiotics, Immune Function, Infection and Inflammation: A Review of the Evidence from Studies Conducted in Humans. Cur Pharma Des 2009;15(13):1428-1518.
A number of studies have been performed examining the influence of various probiotic organisms, either alone or in combination, on immune parameters, infectious outcomes, and inflammatory conditions in humans.
Some components of the immune response, including phagocytosis, natural killer cell activity and mucosal immunoglobulin A production (especially in children), can be improved by some probiotic bacteria. Other components, including lymphocyte proliferation, the production of cytokines and of antibodies other than immunoglobulin A appear less sensitive to probiotics.
Probiotics, including lactobacilli and bifidobacteria, administered to children can reduce incidence and duration of diarrhoea, but the precise effects depend upon the nature of the condition.
Probiotic supplementation can reduce the risk of travellers’ diarrhoea in adults, but does not affect duration. The effect of probiotics on other infectious outcomes is less clear.
Probiotics may benefit children and adults with irritable bowel syndrome and adults with ulcerative colitis; studies in Crohn’s Disease are less clear. Probiotics have little effect in rheumatoid arthritis.
Probiotic supplementation, especially with lactobacilli and bifidobacteria, can reduce risk and severity of allergic disease, particular atopic dermatitis; early supplementation appears to be effective.
Overall, the picture that emerges from studies of probiotics on immune, infectious and inflammatory outcomes in humans is mixed and there appear to be large species and strain differences in effects seen. Other reasons for differences in effects seen will include dose of probiotic organism used, duration of supplementation, characteristics of the subjects studied, sample size, and technical differences in how the measurements were made.
Pitkala K, Strandberg T, Soveri F, et al. Fermented cereal with specific bifidobacteria normalizes bowel movements in elderly nursing home residents. A randomized, controlled trial. J Nutr Health Aging 2007;11(4):305-311.
To assess how fermented oat drink with two selected Bifidobacterium longum strains influences bowel movements among elderly nursing home residents.
A randomized, double-blind, placebo-controlled trial.
12 wards in two nursing homes in Finland.
Wards were randomized to receive daily a fermented oat drink with 1) 109 CFU/day Bifidobacterium longum strains or 2) 109 CFU/day Bifidobacterium lactis Bb12 or 3) without viable bacteria (placebo) for 7 months.
Regularity of bowel movements (no movements or functioning) and consistency of stools (normal, soft or diarrhoea) were recorded for each resident on a daily basis.
The fermented oat drinks were well taken by the subjects, compliance being 85%. The groups receiving active products had more frequent bowel movements than did the placebo group (B. longum group normal functioning 28.5% of follow-up days, B.lactis group 26.9%, and placebo group 20.0%, respectively). The differences between the B. longum and the placebo group (mean 7.1, 95% CI 2.3 – 11.9, p=0.004) and between the B.lactis group and the placebo (mean 6.7, 95% CI 2.5 – 10.9, p = 0.002) were significant even when diarrhoea and constipation in the 3 months prior to the study were used as covariates.
It is possible to normalize bowel movements in frail nursing home.
De Vrese M, Marteau P. Probiotics and Prebiotics: Effects on Diarrhea. J Nutr 2007;137(3):803S–811S.
Probiotics have preventive as well as curative effects on several types of diarrhea of different etiologies.
Prevention and therapy (or alleviation) of diarrhea have been successfully investigated for numerous dietary probiotics to establish probiotic properties and to justify health claims (the medicinal use of probiotic food and the therapy of gastrointestinal diseases itself may not be advertised under current food laws). Other probiotic microorganisms (e.g., Lactobacillus rhamnosus GG, L. reuteri, certain strains of L. casei, L. acidophilus, Escherichia coli strain Nissle 1917, and certain bifidobacteria and enterococci (Enterococcus faecium SF68) as well as the probiotic yeast Saccharomyces boulardii have been investigated with regard to their medicinal use, either as single strains or in mixed-culture probiotics. However, the effects on humans have been assessed mainly in smaller (n < 100) randomized, controlled clinical studies or in open label trials, but large intervention studies and epidemiological investigations of long-term probiotic effects are largely missing. Perhaps with the exception of nosocomial diarrhea or antibiotic-associated diarrhea, the results of these studies are not yet sufficient to give specific recommendations for the clinical use of probiotics in the treatment of diarrhea.
Kotowska, M. et al. Saccharomyces boulardii in the prevention of antibiotic-associated diarrhoea in children: A randomized double-blind placebo-controlled trial. Aliment Pharmacol Ther 2005; 21(5):583-590.
Co-treatment with Saccharomyces boulardii appears to lower the risk of antibiotic-associated diarrhoea in adults receiving broad-spectrum antibiotics.
To determine whether S. boulardii prevents antibiotic-associated diarrhoea in children.
A total of 269 children (aged 6 months to 14 years) with otitis media and/or respiratory tract infections were enrolled in a double-blind, randomized placebo-controlled trial in which they received standard antibiotic treatment plus 250 mg of S. boulardii (experimental group, n = 132) or a placebo (control group, n = 137) orally twice daily for the duration of antibiotic treatment. Analyses were based on allocated treatment and included data from 246 children.
Patients receiving S. boulardii had a lower prevalence of diarrhoea (> or =3 loose or watery stools/day for > or =48 h occurring during or up to 2 weeks after the antibiotic therapy) than those receiving placebo [nine of 119 (8%) vs. 29 of 127 (23%), relative risk: 0.3, 95% confidence interval: 0.2-0.7]. S. boulardii also reduced the risk of antibiotic-associated diarrhoea (diarrhoea caused by Clostridium difficile or otherwise unexplained diarrhoea) compared with placebo [four of 119 (3.4%) vs. 22 of 127 (17.3%), relative risk: 0.2; 95% confidence interval: 0.07-0.5]. No adverse events were observed.
This is the first randomized-controlled trial evidence that S. boulardii effectively reduces the risk of antibiotic-associated diarrhoea in children.
D’Souza AL, et al. Probiotics in prevention of antibiotic associated diarrhoea: meta-analysis. BMJ 2002;324(7350):1361. Review.
To evaluate efficacy of probiotics in prevention and treatment of diarrhoea associated with the use of antibiotics.
Meta-analysis; outcome data (proportion of patients not getting diarrhoea) were analysed, pooled, and compared to determine odds ratios in treated and control groups.
Studies identified by searching Medline between 1966 and 2000 and the Cochrane Library. Studies reviewed nine randomised, double blind, placebo controlled trials of probiotics.
Two of the nine studies investigated the effects of probiotics in children. Four trials used a yeast (Saccharomyces boulardii), four used lactobacilli, and one used a strain of enterococcus that produced lactic acid. Three trials used a combination of probiotic strains of bacteria. In all nine trials, the probiotics were given in combination with antibiotics and the control groups received placebo and antibiotics. The odds ratio in favour of active treatment over placebo in preventing diarrhoea associated with antibiotics was 0.39 (95% confidence interval 0.25 to 0.62; P<0.001) for the yeast and 0.34 (0.19 to 0.61; P<0.01 for lactobacilli. The combined odds ratio was 0.37 (0.26 to 0.53; P<0.001) in favour of active treatment over placebo.
The meta-analysis suggests that probiotics can be used to prevent antibiotic associated diarrhoea and that S boulardii and lactobacilli have the potential to be used in this situation. The efficacy of probiotics in treating antibiotic associated diarrhoea remains to be proved. A further large trial in which probiotics are used as preventive agents should look at the costs of and need for routine use of these agents.
BMJ ’07: Study reports benefit of select probiotics compared to rehydration solution for acute diarrhea in children
Canani RB, et al. Probiotics for treatment of acute diarrhoea in children: Randomised clinical trial of five different preparations. BMJ 2007;335(7615):340.
To compare the efficacy of five probiotic preparations recommended to parents in the treatment of acute diarrhoea in children.
Randomised controlled clinical trial in collaboration with family paediatricians over 12 months.
Children aged 3-36 months visiting a family paediatrician for acute diarrhoea.
Children’s parents were randomly assigned to receive written instructions to purchase a specific probiotic product: oral rehydration solution (control group); Lactobacillus rhamnosus strain GG; Saccharomyces boulardii; Bacillus clausii; mix of L delbrueckii var bulgaricus, Streptococcus thermophilus, L acidophilus, and Bifidobacterium bifidum; or Enterococcus faecium SF68.
MAIN OUTCOME MEASURES:
Primary outcomes were duration of diarrhoea and daily number and consistency of stools. Secondary outcomes were
duration of vomiting and fever and rate of admission to hospital. Safety and tolerance were also recorded.
571 children were allocated to intervention. Median duration of diarrhoea was significantly shorter (P<0.001) in children who received L rhamnosus strain GG (78.5 hours) and the mix of four bacterial strains (70.0 hours) than in children who received oral rehydration solution alone (115.0 hours). One day after the first probiotic administration, the daily number of stools was significantly lower (P<0.001) in children who received L rhamnosus strain GG and in those who received the probiotic mix than in the other groups. The remaining preparations did not affect primary outcomes. Secondary outcomes were similar in all groups.
Not all commercially available probiotic preparations are effective in children with acute diarrhoea. Paediatricians should choose bacterial preparations based on effectiveness data.
Cochrane ’07: Systematic review reports promise for probiotics in children with AAD; strain and dose matter
Johnston BC, et al. Probiotics for the prevention of pediatric antibiotic-associated diarrhea. Danish Cochrane Database Syst Rev. 2007 Apr 18;(2):CD004827.
BACKGROUND: Antibiotics alter the microbial balance within the gastrointestinal tract. Probiotics may prevent antibiotic-associated diarrhea (AAD) via restoration of the gut microflora. Antibiotics are prescribed frequently in children and AAD is common in this population.
OBJECTIVES: To assess the efficacy and adverse effects of probiotics (any specified strain or dose) for the prevention of antibiotic-associated diarrhea in children. To assess adverse events associated with the use of probiotics when co-administered with antibiotics in children.
SEARCH STRATEGY: MEDLINE, EMBASE, CENTRAL, CINAHL , AMED, and the Web of Science (inception to August 2006) were searched along with specialized registers including the Cochrane IBD/FBD Review Group, CISCOM, Chalmers PedCAM Research Register and trial registries from inception to 2005. Letters were sent to authors of included trials, nutra/pharmaceutical companies, and experts in the field requesting additional information on ongoing or unpublished trials. Conference proceedings, dissertation abstracts, and reference lists from included and relevant articles were hand searched.
SELECTION CRITERIA: Randomized, parallel, controlled (placebo, active, or no treatment) trials comparing co-administered probiotics with antibiotics for the prevention of diarrhea secondary to antibiotic use in children (0 to 18 years).
DATA COLLECTION AND ANALYSIS: Methodological quality assessment and data extraction were conducted independently by two authors (BCJ, AS). Dichotomous data (incidence of diarrhea, adverse events) were combined using pooled relative risks, and continuous data (mean duration of diarrhea, mean daily stool frequency) as weighted mean differences, along with their corresponding 95% confidence intervals. Adverse events were summarized using risk difference. For overall pooled results on the incidence of diarrhea, a priori sensitivity analyses included per protocol versus intention to treat, random versus fixed effects, and methodological quality criterion. Subgroup analysis were conducted on probiotic strain, dose, definition of antibiotic-associated diarrhea, and antibiotic agent.
MAIN RESULTS: Ten studies met the inclusion criteria. Trials included treatment with either Lactobacilli spp., Bifidobacterium spp., Streptococcus spp., or Saccharomyces boulardii alone or in combination. Six studies used a single strain probiotic agent and four combined two probiotic strains. The per protocol analysis for 9/10 trials reporting on the incidence of diarrhea show statistically significant results favouring probiotics over active/non active controls (RR 0.49; 95% CI 0.32 to 0.74). However, intention to treat analysis showed non-significant results overall (RR 0.90; 95% CI 0.50 to 1.63). Five of ten trials monitored for adverse events (n = 647); none reported a serious adverse event.
AUTHORS’ CONCLUSIONS: Probiotics show promise for the prevention of pediatric AAD. While per protocol analysis yields treatment effect estimates that are both statistically and clinically significant, as does analysis of high quality studies, the estimate from the intention to treat analysis was not statistically significant.
Future studies should involve probiotic strains and doses with the most promising evidence (e.g., Lactobacillus GG, Lactobacillus sporogenes, Saccharomyces boulardii at 5 to 40 billion colony forming units/day). Research done to date does not permit determination of the effect of age (e.g., infant versus older children) or antibiotic duration (e.g., 5 days versus 10 days).
Future trials would benefit from a validated primary outcome measure for antibiotic-associated diarrhea that is sensitive to change and reflects what treatment effect clinicians, parents, and children consider important. The current data are promising, but it is premature to routinely recommend probiotics for the prevention of pediatric AAD.
Peds ’02: Meta-analysis reports Lactobacillus is safe and effective as a treatment for children with acute diarrhea
van Niel et al. Lactobacillus therapy for acute infectious diarrhea in children: a meta-analysis. Pediatrics. 2002;109(4):678-684.
OBJECTIVE: Childhood diarrhea accounts for substantial morbidity and mortality worldwide. Multiple studies in children have shown that Lactobacillus, administered orally, may have antidiarrheal properties. We conducted a meta-analysis of randomized, controlled studies to assess whether treatment with Lactobacillus improves clinical outcomes in children with acute infectious diarrhea.
METHODS: Studies were sought in bibliographic databases of traditional biomedical as well as complementary and alternative medicine literature published from 1966 to 2000. Search terms were “competitive inhibition,” “diarrhea,” “gastroenteritis,” “Lactobacillus,” “probiotic,” “rotavirus,” and “yog(h)urt.” We included studies that were adequately randomized, blinded, controlled trials in which the treatment group received Lactobacillus and the control group received an adequate placebo and that reported clinical outcome measures of diarrhea intensity. These inclusion criteria were applied by blind review and consensus. The original search yielded 26 studies, 9 of which met the criteria. Multiple observers independently extracted study characteristics and clinical outcomes. Data sufficient to perform meta-analysis of the effect of Lactobacillus on diarrhea duration and diarrhea frequency on day 2 were contained in 7 and 3 of the included studies, respectively.
RESULTS: Summary point estimates indicate a reduction in diarrhea duration of 0.7 days (95% confidence interval: 0.3-1.2 days) and a reduction in diarrhea frequency of 1.6 stools on day 2 of treatment (95% confidence interval: 0.7-2.6 fewer stools) in the participants who received Lactobacillus compared with those who received placebo. Details of treatment protocols varied among the studies. A preplanned subanalysis suggests a dose-effect relationship.
CONCLUSION: The results of this meta-analysis suggest that Lactobacillus is safe and effective as a treatment for children with acute infectious diarrhea.
Ali Pharm Ther ’03: CRT shows less abdominal bloating in patients with IBS with higher dose probiotic blend
Kim HJ, et al. A randomized controlled trial of a probiotic, VSL#3, on gut transit and symptoms in diarrhoea-predominant irritable bowel syndrome. Aliment Pharmacol Ther 2003;17(7):895-904.
AIM: To investigate the effects of a probiotic formulation, VSL#3, on gastrointestinal transit and symptoms of patients with Rome II irritable bowel syndrome with predominant diarrhoea.
METHODS: Twenty-five patients with diarrhoea-predominant irritable bowel syndrome were randomly assigned to receive VSL#3 powder (450 billion lyophilized bacteria/day) or matching placebo twice daily for 8 weeks after a 2-week run-in period. Pre- and post-treatment gastrointestinal transit measurements were performed in all patients. Patients recorded their bowel function and symptoms daily in a diary during the 10-week study, which was powered to detect a 50% change in the primary colonic transit end-point.
RESULTS: There were no significant differences in mean gastrointestinal transit measurements, bowel function scores or satisfactory global symptom relief between the two treatment groups, pre- or post-therapy. Differences in abdominal bloating scores between treatments were borderline significant (P = 0.09, analysis of covariance). Further analysis revealed that abdominal bloating was reduced (P = 0.046) with VSL#3 [mean post- minus pre-treatment score, - 13.7; 95% confidence interval (CI), - 2.5 to - 24.9], but not with placebo (P = 0.54) (mean post- minus pre-treatment score, – 1.7; 95% CI, 7.1 to – 10.4). With the exception of changes in abdominal bloating, VSL#3 had no effect on other individual symptoms: abdominal pain, gas and urgency. All patients tolerated VSL#3 well.
CONCLUSION: VSL#3 appears to be promising in the relief of abdominal bloating in patients with diarrhoea-predominant irritable bowel syndrome. This is unrelated to an alteration in gastrointestinal or colonic transit.
Cunningham-Rundles, S, et al. (2000). Probiotics and immune response. Am. J. Gastroenterol 2000;95(1):S22–S25.
Current evidence supports the concept that oral administration of probiotic lactobacilli may be therapeutic in preventing antibiotic-associated diarrhea in children and in reestablishing normal flora in the gastrointestinal tract.
Children with human immunodeficiency virus (HIV) infections may have episodes of diarrhea and frequently experience malabsorption associated with possible bacterial overgrowth; together these may interact to produce the growth abnormalities characteristic of this group.
The overall objective of this investigation has been to determine whether oral administration of the probiotic Lactobacillus plantarum 299v could improve nutrient status and promote growth in children congenitally exposed to HIV. In addition, the possible beneficial effect of Lactobacillus plantarum 299v in modulating immune response was evaluated.
In preliminary results described here, we report on the ability of Lactobacillus plantarum 299v to colonize children with HIV and to elicit specific systemic immune response after oral supplementation.